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Journal articles on the topic 'Neuroblastes'
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1
Cabet, Sara, Laurent Guibaud, and Damien Sanlaville. "Variations pathogènes de NDE1 et microlissencéphalie." médecine/sciences 36, no. 10 (October 2020): 866–71. http://dx.doi.org/10.1051/medsci/2020157.
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Les variants pathogènes du gène NDE1 sont responsables de microlissencéphalies chez l’homme et constituent le déficit de la neurogenèse le plus sévère décrit à ce jour. Le gène NDE1 code une phosphoprotéine essentielle à la neurogenèse, qui est exprimée dans différents compartiments cellulaires des neuroblastes. Le mécanisme physiopathologique précis de la microlissencéphalie n’est pas encore complètement élucidé. Plus de 60 partenaires d’interaction protéique avec NDE1 ont été rapportés, notamment des protéines impliquées dans la formation du fuseau mitotique, la ciliation, la protection du génome des neuroblastes en division ou encore l’apoptose (la LIS1, la dynéine, la cohésine) et constituent autant de pistes explorées dans cette revue.
2
Broadus, J., and C. Q. Doe. "Evolution of neuroblast identity: seven-up and prospero expression reveal homologous and divergent neuroblast fates in Drosophila and Schistocerca." Development 121, no. 12 (December 1, 1995): 3989–96. http://dx.doi.org/10.1242/dev.121.12.3989.
Full textAbstract:
In the Drosophila CNS, early neuroblast formation and fate are controlled by the pair-rule class of segmentation genes. The distantly related Schistocerca (grasshopper) embryo has a similar arrangement of neuroblasts, despite lack of known pair-rule gene function. Does divergent pair-rule gene function lead to different neuroblast identities, or can different patterning mechanisms produce homologous neuroblasts? We use four molecular markers to compare Drosophila and Schistocerca neuroblast identity: seven-up, prospero, engrailed, and fushi-tarazu/Dax. In both insects some early-forming neuroblasts share key features of neuroblast identity (position, time of formation, and temporally accurate gene expression); thus, different patterning mechanisms can generate similar neuroblast fates. In contrast, several later-forming neuroblasts show species-specific differences in position and/or gene expression; these neuroblast identities seem to have diverged, suggesting that evolution of the insect central nervous system can occur through changes in embryonic neuroblast identity.
3
Skeath, J. B. "The Drosophila EGF receptor controls the formation and specification of neuroblasts along the dorsal-ventral axis of the Drosophila embryo." Development 125, no. 17 (September 1, 1998): 3301–12. http://dx.doi.org/10.1242/dev.125.17.3301.
Full textAbstract:
The segmented portion of the Drosophila embryonic central nervous system develops from a bilaterally symmetrical, segmentally reiterated array of 30 unique neural stem cells, called neuroblasts. The first 15 neuroblasts form about 30–60 minutes after gastrulation in two sequential waves of neuroblast segregation and are arranged in three dorsoventral columns and four anteroposterior rows per hemisegment. Each neuroblast acquires a unique identity, based on gene expression and the unique and nearly invariant cell lineage it produces. Recent experiments indicate that the segmentation genes specify neuroblast identity along the AP axis. However, little is known as to the control of neuroblast identity along the DV axis. Here, I show that the Drosophila EGF receptor (encoded by the DER gene) promotes the formation, patterning and individual fate specification of early forming neuroblasts along the DV axis. Specifically, I use molecular markers that identify particular neuroectodermal domains, all neuroblasts or individual neuroblasts, to show that in DER mutant embryos (1) intermediate column neuroblasts do not form, (2) medial column neuroblasts often acquire identities inappropriate for their position, while (3) lateral neuroblasts develop normally. Furthermore, I show that active DER signaling occurs in the regions from which the medial and intermediate neuroblasts will later delaminate. In addition, I demonstrate that the concomitant loss of rhomboid and vein yield CNS phenotypes indistinguishable from DER mutant embryos, even though loss of either gene alone yields minor CNS phenotypes. These results demonstrate that DER plays a critical role during neuroblast formation, patterning and specification along the DV axis within the developing Drosophila embryonic CNS.
4
McDonald, J. A., and C. Q. Doe. "Establishing neuroblast-specific gene expression in the Drosophila CNS: huckebein is activated by Wingless and Hedgehog and repressed by Engrailed and Gooseberry." Development 124, no. 5 (March 1, 1997): 1079–87. http://dx.doi.org/10.1242/dev.124.5.1079.
Full textAbstract:
The Drosophila ventral neuroectoderm produces a stereotyped array of central nervous system precursors, called neuroblasts. Each neuroblast has a unique identity based on its position, pattern of gene expression and cell lineage. To understand how neuronal diversity is generated, we need to learn how neuroblast-specific gene expression is established, and how these genes control cell fate within neuroblast lineages. Here we address the first question: how is neuroblast-specific gene expression established? We focus on the huckebein gene, because it is expressed in a subset of neuroblasts and is required for aspects of neuronal and glial determination. We show that Huckebein is a nuclear protein first detected in small clusters of neuroectodermal cells and then in a subset of neuroblasts. The secreted Wingless and Hedgehog proteins activate huckebein expression in distinct but overlapping clusters of neuroectodermal cells and neuroblasts, whereas the nuclear Engrailed and Gooseberry proteins repress huckebein expression in specific regions of neuroectoderm or neuroblasts. Integration of these activation and repression inputs is required to establish the precise neuroectodermal pattern of huckebein, which is subsequently required for the development of specific neuroblast cell lineages.
5
Doe, C. Q. "Molecular markers for identified neuroblasts and ganglion mother cells in the Drosophila central nervous system." Development 116, no. 4 (December 1, 1992): 855–63. http://dx.doi.org/10.1242/dev.116.4.855.
Full textAbstract:
The first step in generating cellular diversity in the Drosophila central nervous system is the formation of a segmentally reiterated array of neural precursor cells, called neuroblasts. Subsequently, each neuroblast goes through an invariant cell lineage to generate neurons and/or glia. Using molecular lineage markers, I show that (1) each neuroblast forms at a stereotyped time and position; (2) the neuroblast pattern is indistinguishable between thoracic and abdominal segments; (3) the development of individual neuroblasts can be followed throughout early neurogenesis; (4) gene expression in a neuroblast can be reproducibly modulated during its cell lineage; (5) identified ganglion mother cells form at stereotyped times and positions; and (6) the cell lineage of four well-characterized neurons can be traced back to two identified neuroblasts. These results set the stage for investigating neuroblast specification and the mechanisms controlling neuroblast cell lineages.
6
Dormand, E. L., and A. H. Brand. "Runt determines cell fates in the Drosophila embryonic CNS." Development 125, no. 9 (May 1, 1998): 1659–67. http://dx.doi.org/10.1242/dev.125.9.1659.
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The segmentation gene, runt, is expressed by a subset of the 30 neuroblasts that give rise to each neuromere of the Drosophila embryo. Runt activity in the neuroblasts is necessary for expression of even-skipped in the EL neurons. runt is therefore a good candidate for a gene specifying neuroblast identities. We have ectopically expressed Runt in restricted subsets of neuroblasts and show that Runt is sufficient to activate even-skipped expression in the progeny of specific neuroblasts. Using the marker Tau-green fluorescent protein to highlight the axons, we have found that the extra Even-skipped-expressing neurons project axons along the same pathway as the EL neurons. We find that Runt is expressed in neuroblast 3–3, supporting an autonomous role for runt during neuroblast specification.
7
Giansanti, M. G., M. Gatti, and S. Bonaccorsi. "The role of centrosomes and astral microtubules during asymmetric division of Drosophila neuroblasts." Development 128, no. 7 (April 1, 2001): 1137–45. http://dx.doi.org/10.1242/dev.128.7.1137.
Full textAbstract:
Drosophila neuroblasts are stem cells that divide asymmetrically to produce another large neuroblast and a smaller ganglion mother cell (GMC). During neuroblast division, several cell fate determinants, such as Miranda, Prospero and Numb, are preferentially segregated into the GMC, ensuring its correct developmental fate. The accurate segregation of these determinants relies on proper orientation of the mitotic spindle within the dividing neuroblast, and on the correct positioning of the cleavage plane. In this study we have analyzed the role of centrosomes and astral microtubules in neuroblast spindle orientation and cytokinesis. We examined neuroblast division in asterless (asl) mutants, which, although devoid of functional centrosomes and astral microtubules, form well-focused anastral spindles that undergo anaphase and telophase. We show that asl neuroblasts assemble a normal cytokinetic ring around the central spindle midzone and undergo unequal cytokinesis. Thus, astral microtubules are not required for either signaling or positioning cytokinesis in Drosophila neuroblasts. Our results indicate that the cleavage plane is dictated by the positioning of the central spindle midzone within the cell, and suggest a model on how the central spindle attains an asymmetric position during neuroblast mitosis. We have also analyzed the localization of Miranda during mitotic division of asl neuroblasts. This protein accumulates in morphologically regular cortical crescents but these crescents are mislocalized with respect to the spindle orientation. This suggests that astral microtubules mediate proper spindle rotation during neuroblast division.
8
Cui, X., and C. Q. Doe. "The role of the cell cycle and cytokinesis in regulating neuroblast sublineage gene expression in the Drosophila CNS." Development 121, no. 10 (October 1, 1995): 3233–43. http://dx.doi.org/10.1242/dev.121.10.3233.
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The precise temporal control of gene expression is critical for specifying neuronal identity in the Drosophila central nervous system (CNS). A particularly interesting class of genes are those expressed at stereotyped times during the cell lineage of identified neural precursors (neuroblasts): these are termed ‘sublineage’ genes. Although sublineage gene function is vital for CNS development, the temporal regulation of this class of genes has not been studied. Here we show that four genes (ming, even-skipped, unplugged and achaete) are expressed in specific neuroblast sublineages. We show that these neuroblasts can be identified in embryos lacking both neuroblast cytokinesis and cell cycle progression (string mutants) and in embryos lacking only neuroblast cytokinesis (pebble mutants). We find that the unplugged and achaete genes are expressed normally in string and pebble mutant embryos, indicating that temporal control is independent of neuroblast cytokinesis or counting cell cycles. In contrast, neuroblasts require cytokinesis to activate sublineage ming expression, while a single, identified neuroblast requires cell cycle progression to activate even-skipped expression. These results suggest that neuroblasts have an intrinsic gene regulatory hierarchy controlling unplugged and achaete expression, but that cell cycle- or cytokinesis-dependent mechanisms are required for ming and eve CNS expression.
9
Udolph, G., J. Urban, G. Rusing, K. Luer, and G. M. Technau. "Differential effects of EGF receptor signalling on neuroblast lineages along the dorsoventral axis of the Drosophila CNS." Development 125, no. 17 (September 1, 1998): 3291–99. http://dx.doi.org/10.1242/dev.125.17.3291.
Full textAbstract:
The Drosophila ventral nerve cord derives from a stereotype population of about 30 neural stem cells, the neuroblasts, per hemineuromere. Previous experiments provided indications for inductive signals at ventral sites of the neuroectoderm that confer neuroblast identities. Using cell lineage analysis, molecular markers and cell transplantation, we show here that EGF receptor signalling plays an instructive role in CNS patterning and exerts differential effects on dorsoventral subpopulations of neuroblasts. The Drosophila EGF receptor (DER) is capable of cell autonomously specifiying medial and intermediate neuroblast cell fates. DER signalling appears to be most critical for proper development of intermediate neuroblasts and less important for medial neuroblasts. It is not required for lateral neuroblast lineages or for cells to adopt CNS midline cell fate. Thus, dorsoventral patterning of the CNS involves both DER-dependent and -independent regulatory pathways. Furthermore, we discuss the possibility that different phases of DER activation exist during neuroectodermal patterning with an early phase independent of midline-derived signals.
10
Berger, Christian, Joachim Urban, and Gerhard M. Technau. "Stage-specific inductive signals in the Drosophila neuroectoderm control the temporal sequence of neuroblast specification." Development 128, no. 17 (September 1, 2001): 3243–51. http://dx.doi.org/10.1242/dev.128.17.3243.
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One of the initial steps of neurogenesis in the Drosophila embryo is the delamination of a stereotype set of neural progenitor cells (neuroblasts) from the neuroectoderm. The time window of neuroblast segregation has been divided into five successive waves (S1-S5) in which subsets of neuroblasts with specific identities are formed. To test when identity specification of the various neuroblasts takes place and whether extrinsic signals are involved, we have performed heterochronic transplantation experiments. Single neuroectodermal cells from stage 10 donor embryos (after S2) were transplanted into the neuroectoderm of host embryos at stage 7 (before S1) and vice versa. The fate of these cells was uncovered by their lineages at stage 16/17. Transplanted cells adjusted their fate to the new temporal situation. Late neuroectodermal cells were able to take over the fate of early (S1/S2) neuroblasts. The early neuroectodermal cells preferentially generated late (S4/S5) neuroblasts, despite their reduced time of exposure to the neuroectoderm. Furthermore, neuroblast fates are independent from divisions of neuroectodermal progenitor cells. We conclude from these experiments that neuroblast specification occurs sequentially under the control of non-cell-autonomous and stage-specific inductive signals that act in the neuroectoderm.
11
Cui, X., and C. Q. Doe. "ming is expressed in neuroblast sublineages and regulates gene expression in the Drosophila central nervous system." Development 116, no. 4 (December 1, 1992): 943–52. http://dx.doi.org/10.1242/dev.116.4.943.
Full textAbstract:
Cell diversity in the Drosophila central nervous system (CNS) is primarily generated by the invariant lineage of neural precursors called neuroblasts. We used an enhancer trap screen to identify the ming gene, which is transiently expressed in a subset of neuroblasts at reproducible points in their cell lineage (i.e. in neuroblast ‘sublineages’), suggesting that neuroblast identity can be altered during its cell lineage. ming encodes a predicted zinc finger protein and loss of ming function results in precise alterations in CNS gene expression, defects in axonogenesis and embryonic lethality. We propose that ming controls cell fate within neuroblast cell lineages.
12
Munroe, Jordan A., Mubarak H. Syed, and Chris Q. Doe. "Imp is required for timely exit from quiescence in Drosophila type II neuroblasts." PLOS ONE 17, no. 12 (December 15, 2022): e0272177. http://dx.doi.org/10.1371/journal.pone.0272177.
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Stem cells must balance proliferation and quiescence, with excess proliferation favoring tumor formation, and premature quiescence preventing proper organogenesis. Drosophila brain neuroblasts are a model for investigating neural stem cell entry and exit from quiescence. Neuroblasts begin proliferating during embryogenesis, enter quiescence prior to larval hatching, and resume proliferation 12-30h after larval hatching. Here we focus on the mechanism used to exit quiescence, focusing on "type II" neuroblasts. There are 16 type II neuroblasts in the brain, and they undergo the same cycle of embryonic proliferation, quiescence, and proliferation as do most other brain neuroblasts. We focus on type II neuroblasts due to their similar lineage as outer radial glia in primates (both have extended lineages with intermediate neural progenitors), and because of the availability of specific markers for type II neuroblasts and their progeny. Here we characterize the role of Insulin-like growth factor II mRNA-binding protein (Imp) in type II neuroblast proliferation and quiescence. Imp has previously been shown to promote proliferation in type II neuroblasts, in part by acting antagonistically to another RNA-binding protein called Syncrip (Syp). Here we show that reducing Imp levels delays exit from quiescence in type II neuroblasts, acting independently of Syp, with Syp levels remaining low in both quiescent and newly proliferating type II neuroblasts. We conclude that Imp promotes exit from quiescence, a function closely related to its known role in promoting neuroblast proliferation.
13
Datta, S. "Control of proliferation activation in quiescent neuroblasts of the Drosophila central nervous system." Development 121, no. 4 (April 1, 1995): 1173–82. http://dx.doi.org/10.1242/dev.121.4.1173.
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Stem cell proliferation is controlled through cell cycle arrest and activation. In the central nervous system of Drosophila melanogaster, neuroblast quiescence and activation takes place in defined spatial and temporal patterns. Two genes have been identified that regulate the pattern of neuroblast quiescence and proliferation. ana, which has been previously described by Ebens and coworkers (Ebens, A., Garren, H., Cheyette, B. N. R. and Zipursky, S. L. (1993). Cell 74, 15–28), encodes a secreted glial glycoprotein that inhibits premature neuroblast proliferation. We previously showed that trolsd causes a dramatic drop in the number of dividing cells in the larval brain late in development. This study presents evidence that this decrease results from a failure to activate proliferation in the quiescent neuroblast population at the appropriate time. However, trolsd does not affect the maintenance of cell division in already dividing mushroom body neuroblasts. The quiescent optic lobe and thoracic neuroblasts affected by trolsd proliferate in a trol mutant background if they have been activated by a lack of the ana proliferation repressor, demonstrating that trolsd does not affect cellular viability, nor does trol represent a celltype-specific mitotic factor. This also shows that trol acts downstream of ana to activate proliferation of quiescent neuroblasts in an ana-dependent pathway, possibly by inactivating or bypassing the ana repressor. These results suggest that trol and ana are components of a novel developmental pathway for the control of cell cycle activation in quiescent neuroblasts.
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Schmid, A., A. Chiba, and C. Q. Doe. "Clonal analysis of Drosophila embryonic neuroblasts: neural cell types, axon projections and muscle targets." Development 126, no. 21 (November 1, 1999): 4653–89. http://dx.doi.org/10.1242/dev.126.21.4653.
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An experimental analysis of neurogenesis requires a detailed understanding of wild-type neural development. Recent DiI cell lineage studies have begun to elucidate the family of neurons and glia produced by each Drosophila embryonic neural precursor (neuroblast). Here we use DiI labeling to extend and clarify previous studies, but our analysis differs from previous studies in four major features: we analyze and compare lineages of every known embryonic neuroblast; we use an in vivo landmark (engrailed-GFP) to increase the accuracy of neuroblast identification; we use confocal fluorescence and Nomarski microscopy to collect three-dimensional data in living embryos simultaneously for each DiI-labeled clone, the engrailed-GFP landmark, and the entire CNS and muscle target field (Nomarski images); and finally, we analyze clones very late in embryonic development, which reveals novel cell types and axon/dendrite complexity. We identify the parental neuroblasts for all the cell types of the embryonic CNS: motoneurons, intersegmental interneurons, local interneurons, glia and neurosecretory cells (whose origins had never been determined). We identify muscle contacts for every thoracic and abdominal motoneuron at stage 17. We define the parental neuroblasts for neurons or glia expressing well-known molecular markers or neurotransmitters. We correlate Drosophila cell lineage data with information derived from other insects. In addition, we make the following novel conclusions: (1) neuroblasts at similar dorsoventral positions, but not anteroposterior positions, often generate similar cell lineages, and (2) neuroblasts at similar dorsoventral positions often produce the same motoneuron subtype: ventral neuroblasts typically generate motoneurons with dorsal muscle targets, while dorsal neuroblasts produce motoneurons with ventral muscle targets. Lineage data and movies can be found at http://www.biologists.com/Development/movies/dev8623.htmlhttp://www.neuro.uoregon.edu/doelab/lineages/
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Matsuzaki, F., T. Ohshiro, H. Ikeshima-Kataoka, and H. Izumi. "miranda localizes staufen and prospero asymmetrically in mitotic neuroblasts and epithelial cells in early Drosophila embryogenesis." Development 125, no. 20 (October 15, 1998): 4089–98. http://dx.doi.org/10.1242/dev.125.20.4089.
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When neuroblasts divide, prospero protein and mRNA segregate asymmetrically into the daughter neuroblast and sibling ganglion mother cell. miranda is known to localize prospero protein to the basal cell cortex of neuroblasts while the staufen RNA-binding protein mediates prospero mRNA localization. Here we show that miranda is required for asymmetric staufen localization in neuroblasts. Analyses using miranda mutants reveal that prospero and staufen interact with miranda under the same cell-cycle-dependent control. miranda thus acts to partition both prospero protein and mRNA. Furthermore, miranda localizes prospero and staufen to the basolateral cortex in dividing epithelial cells, which express the three proteins prior to neurogenesis. Our observations suggest that the epithelial cell and neuroblast (both of epithelial origin) share the same molecular machinery for creating cellular asymmetry.
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Skeath, J. B., G. F. Panganiban, and S. B. Carroll. "The ventral nervous system defective gene controls proneural gene expression at two distinct steps during neuroblast formation in Drosophila." Development 120, no. 6 (June 1, 1994): 1517–24. http://dx.doi.org/10.1242/dev.120.6.1517.
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Within the Drosophila embryo, the formation of many neuroblasts depends on the functions of the proneural genes of the achaete-scute complex (AS-C): achaete (ac), scute (sc) and lethal of scute (l'sc), and the gene ventral nervous system defective (vnd). Here, we show that vnd controls neuroblast formation, in part, through its regulation of the proneural genes of the AS-C. vnd is absolutely required to activate ac, sc and l'sc gene expression in proneural clusters in specific domains along the medial column of the earliest arising neuroblasts. Using ac-lacZ reporter constructs, we determined that vnd controls proneural gene expression at two distinct steps during neuroblast formation through separable regulatory regions. First, vnd is required to activate proneural cluster formation within the medial column of every other neuroblast row through regulatory elements located 3′ to ac; second, through a 5′ regulatory region, vnd functions to increase or maintain proneural gene expression in the cell within the proneural cluster that normally becomes the neuroblast. By following neuroblast segregation in vnd mutant embryos, we show that the neuroectoderm forms normally and that the defects in neuroblast formation are specific to particular proneural clusters.
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Chu-Lagraff, Quynh, Dorthy M. Wright, Leslie Klis McNeil, and Chris Q. Doe. "The prospero gene encodes a divergent homeodomain protein that controls neuronal identity in Drosophila." Development 113, Supplement_2 (April 1, 1991): 79–85. http://dx.doi.org/10.1242/dev.113.supplement_2.79.
Full textAbstract:
The Drosophila central nervous system (CNS) develops from a population of stem cells called neuroblasts; each neuroblast goes through an invariant cell lineage to produce a characteristic family of neurons or glia. We are interested in the molecular mechanisms controlling neuroblast cell lineage. Recently we identified the prospero (pros) gene, which is expressed in embryonic neuroblasts. Loss of pros function results in aberrant expression of the homeobox genes fushi tarazu, evenskipped and engrailed in a subset of neuroblast progeny, suggesting that pros plays an early and fundamental role in the specification of neuronal fate (Doe et al. 1991). Here we show that the pros gene encodes a highly divergent homeodomain. The homeodomain contains several of the most conserved amino acids characteristic of known homeodomains, yet it is considerably less basic than previously identified homeodomains. These data are consistent with a model in which pros controls neuroblast cell lineages by regulating gene expression.
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Matsuzaki, M., and K. Saigo. "hedgehog signaling independent of engrailed and wingless required for post-S1 neuroblast formation in Drosophila CNS." Development 122, no. 11 (November 1, 1996): 3567–75. http://dx.doi.org/10.1242/dev.122.11.3567.
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The hedgehog gene product, secreted from engrailed-expressing neuroectoderm, is required for the formation of post-S1 neuroblasts in rows 2, 5 and 6. The hedgehog protein functions not only as a paracrine but also as an autocrine factor and its transient action on the neuroectoderm 1–2 hours (at 18 degrees C) prior to neuroblast delamination is necessary and sufficient to form normal neuroblasts. In contrast to epidermal development, hedgehog expression required for neuroblast formation is regulated by neither engrailed nor wingless. hedgehog and wingless bestow composite positional cues on the neuroectodermal regions for S2-S4 neuroblasts at virtually the same time and, consequently, post-S1 neuroblasts in different rows can acquire different positional values along the anterior-posterior axis. The average number of proneural cells for each of three eagle-positive S4-S5 neuroblasts was found to be 5–9, the same for S1 NBs. As with wingless (Chu-LaGraff et al., Neuron 15, 1041–1051, 1995), huckebein expression in putative proneural regions for certain post-S1 neuroblasts is under the control of hedgehog. hedgehog and wingless are involved in separate, parallel pathways and loss of either is compensated for by the other in NB 7–3 formation. NBs 6–4 and 7–3, arising from the engrailed domain, were also found to be specified by the differential expression of two homeobox genes, gooseberry-distal and engrailed.
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Martončíková, Marcela, Anna Alexovič Matiašová, Juraj Ševc, and Enikő Račeková. "Relationship between Blood Vessels and Migration of Neuroblasts in the Olfactory Neurogenic Region of the Rodent Brain." International Journal of Molecular Sciences 22, no. 21 (October 25, 2021): 11506. http://dx.doi.org/10.3390/ijms222111506.
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Neural precursors originating in the subventricular zone (SVZ), the largest neurogenic region of the adult brain, migrate several millimeters along a restricted migratory pathway, the rostral migratory stream (RMS), toward the olfactory bulb (OB), where they differentiate into interneurons and integrate into the local neuronal circuits. Migration of SVZ-derived neuroblasts in the adult brain differs in many aspects from that in the embryonic period. Unlike in that period, postnatally-generated neuroblasts in the SVZ are able to divide during migration along the RMS, as well as they migrate independently of radial glia. The homophilic mode of migration, i.e., using each other to move, is typical for neuroblast movement in the RMS. In addition, it has recently been demonstrated that specifically-arranged blood vessels navigate SVZ-derived neuroblasts to the OB and provide signals which promote migration. Here we review the development of vasculature in the presumptive neurogenic region of the rodent brain during the embryonic period as well as the development of the vascular scaffold guiding neuroblast migration in the postnatal period, and the significance of blood vessel reorganization during the early postnatal period for proper migration of RMS neuroblasts in adulthood.
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Kaneko, N., V. Herranz-Pérez, T. Otsuka, H. Sano, N. Ohno, T. Omata, H. B. Nguyen, et al. "New neurons use Slit-Robo signaling to migrate through the glial meshwork and approach a lesion for functional regeneration." Science Advances 4, no. 12 (December 2018): eaav0618. http://dx.doi.org/10.1126/sciadv.aav0618.
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After brain injury, neural stem cell–derived neuronal precursors (neuroblasts) in the ventricular-subventricular zone migrate toward the lesion. However, the ability of the mammalian brain to regenerate neuronal circuits for functional recovery is quite limited. Here, using a mouse model for ischemic stroke, we show that neuroblast migration is restricted by reactive astrocytes in and around the lesion. To migrate, the neuroblasts use Slit1-Robo2 signaling to disrupt the actin cytoskeleton in reactive astrocytes at the site of contact. Slit1-overexpressing neuroblasts transplanted into the poststroke brain migrated closer to the lesion than did control neuroblasts. These neuroblasts matured into striatal neurons and efficiently regenerated neuronal circuits, resulting in functional recovery in the poststroke mice. These results suggest that the positioning of new neurons will be critical for functional neuronal regeneration in stem/progenitor cell–based therapies for brain injury.
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Spana, E. P., and C. Q. Doe. "The prospero transcription factor is asymmetrically localized to the cell cortex during neuroblast mitosis in Drosophila." Development 121, no. 10 (October 1, 1995): 3187–95. http://dx.doi.org/10.1242/dev.121.10.3187.
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Both intrinsic and extrinsic factors are known to regulate sibling cell fate. Here we describe a novel mechanism for the asymmetric localization of a transcription factor to one daughter cell at mitosis. The Drosophila CNS develops from asymmetrically dividing neuroblasts, which give rise to a large neuroblast and a smaller ganglion mother cell (GMC). The prospero gene encodes a transcription factor necessary for proper GMC gene expression. We show that the prospero protein is synthesized in the neuroblast where it is localized to the F-actin cell cortex. At mitosis, prospero is asymmetrically localized to the budding GMC and excluded from the neuroblast. After cytokinesis, prospero is translocated from the GMC cortex into the nucleus. Asymmetric cortical localization of prospero in neuroblasts requires entry into mitosis; it does not depend on numb function. prospero is also observed in cortical crescents in dividing precursors of the peripheral nervous system and adult midgut. The asymmetric cortical localization of prospero at mitosis is a mechanism for rapidly establishing distinct sibling cell fates in the CNS and possibly other tissues.
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Zalucki, Oressia, Lachlan Harris, Tracey J. Harvey, Danyon Harkins, Jocelyn Widagdo, Sabrina Oishi, Elise Matuzelski, et al. "NFIX-Mediated Inhibition of Neuroblast Branching Regulates Migration Within the Adult Mouse Ventricular–Subventricular Zone." Cerebral Cortex 29, no. 8 (October 1, 2018): 3590–604. http://dx.doi.org/10.1093/cercor/bhy233.
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Abstract Understanding the migration of newborn neurons within the brain presents a major challenge in contemporary biology. Neuronal migration is widespread within the developing brain but is also important within the adult brain. For instance, stem cells within the ventricular–subventricular zone (V-SVZ) and the subgranular zone of dentate gyrus of the adult rodent brain produce neuroblasts that migrate to the olfactory bulb and granule cell layer of the dentate gyrus, respectively, where they regulate key brain functions including innate olfactory responses, learning, and memory. Critically, our understanding of the factors mediating neuroblast migration remains limited. The transcription factor nuclear factor I X (NFIX) has previously been implicated in embryonic cortical development. Here, we employed conditional ablation of Nfix from the adult mouse brain and demonstrated that the removal of this gene from either neural stem and progenitor cells, or neuroblasts, within the V-SVZ culminated in neuroblast migration defects. Mechanistically, we identified aberrant neuroblast branching, due in part to increased expression of the guanylyl cyclase natriuretic peptide receptor 2 (Npr2), as a factor contributing to abnormal migration in Nfix-deficient adult mice. Collectively, these data provide new insights into how neuroblast migration is regulated at a transcriptional level within the adult brain.
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Dober, Stranzinger, Kellenberger, and Huisman. "Säugling mit Brillenhämatom – Trauma oder Tumor?" Praxis 96, no. 20 (May 1, 2007): 811–14. http://dx.doi.org/10.1024/1661-8157.96.20.811.
Full textAbstract:
Wir berichten von einem bisher gesunden 11 Monate alten Jungen, welcher sich mit einer progredienten supraorbitalen Schwellung links, periorbitaler Ekchymose, Hepatosplenomegalie und B-Symptomatik präsentierte. Die klinische, laborchemische und bildgebende Diagnostik zeigte ein Neuroblastom. Das Neuroblastom ist neben Hirntumoren die häufigste solide Raumforderung im Säuglingsalter. Klinische Anzeichen für ein Neuroblastom sind unspezifisch. Die bei unserem Patienten gefundenen so genannten «raccoon eyes» sind Ausdruck der orbitalen Metastasierung und können initial den Verdacht auf eine Kindsmisshandlung lenken. Die Prognose des Neuroblastoms ist abhängig vom Tumorstadium und dem Alter des Kindes.
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Taylor, B. J., and J. W. Truman. "Commitment of abdominal neuroblasts in Drosophila to a male or female fate is dependent on genes of the sex-determining hierarchy." Development 114, no. 3 (March 1, 1992): 625–42. http://dx.doi.org/10.1242/dev.114.3.625.
Full textAbstract:
Adult specific neurons in the central nervous system of holometabolous insects are generated by the postembryonic divisions of neuronal stem cells (neuroblasts). In the ventral nervous system of Drosophila melanogaster, sex-specific divisions by a set of abdominal neuroblasts occur during larval and early pupal stages. Animals mutant for several sex-determining genes were analyzed to determine the genetic regulation of neuroblast commitment to the male or female pattern of division and the time during development when these decisions are made. We have found that the choice of the sexual pathway taken by sex-specific neuroblasts depends on the expression of one of these genes, doublesex (dsx). In the absence of any functional dxs+ products, the sex-specific neuroblasts fail to undergo any postembryonic divisions in male or female larval nervous systems. From the analysis of intersexes generated by dominant alleles of dsx, it has been concluded that the same neuroblasts provide the sex-specific neuroblasts in both male and female central nervous systems. The time when neuroblasts become committed to generate their sex-specific divisions were identified by shifting tra-2ts flies between the male- and female-specifying temperatures at various times during larval development. Neuroblasts become determined to adopt a male or female state at the end of the first larval instar, a time when abdominal neuroblasts enter their first postembryonic S-phase.
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Cerezo-Guisado, Maria Isabel, Natalia GarcíA-Román, Luis Jesús García-MaríN, Alberto Álvarez-Barrientos, Maria Julia Bragado, and Maria Jesús Lorenzo. "Lovastatin inhibits the extracellular-signal-regulated kinase pathway in immortalized rat brain neuroblasts." Biochemical Journal 401, no. 1 (December 11, 2006): 175–83. http://dx.doi.org/10.1042/bj20060731.
Full textAbstract:
We have shown previously that lovastatin, a 3-hydroxy-3-methyl- glutaryl coenzyme A reductase inhibitor, induces apoptosis in spontaneously immortalized rat brain neuroblasts. In the present study, we analysed the intracellular signal transduction pathways by which lovastatin induces neuroblast apoptosis. We showed that lovastatin efficiently inhibited Ras activation, which was associ-ated with a significant decrease in ERK1/2 (extracellular-signal-regulated kinase 1/2) phosphorylation. Lovastatin also decreased CREB phosphorylation and CREB-mediated gene expression. The effects of lovastatin on the Ras/ERK1/2/CREB pathway were time- and concentration-dependent and fully prevented by meva-lonate. In addition, we showed that two MEK [MAPK (mitogen-activated protein kinase)/ERK kinase] inhibitors, PD98059 and PD184352, were poor inducers of apoptosis in serum-treated neuroblasts. However, these inhibitors significantly increased apop-tosis induced by lovastatin treatment. Furthermore, we showed that pharmacological inhibition of both MEK and phosphoinos-itide 3-kinase activities was able to induce neuroblast apoptosis with similar efficacy as lovastatin. Our results suggest that lovast-atin triggers neuroblast apoptosis by regulating several signalling pathways, including the Ras/ERK1/2 pathway. These findings might also contribute to elucidate the intracellular mechanisms involved in the central nervous system side effects associated with statin therapy.
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Zacharias, D., J. Leslie, D. Williams, T. Meier, and H. Reichert. "Neurogenesis in the insect brain: cellular identification and molecular characterization of brain neuroblasts in the grasshopper embryo." Development 118, no. 3 (July 1, 1993): 941–55. http://dx.doi.org/10.1242/dev.118.3.941.
Full textAbstract:
Brain neuroblasts in the embryonic grasshopper were studied by toluidine blue staining, BrdU incorporation, and immunocytochemistry in whole-mounts as well as by reconstruction of stained serial sections. Large dividing neuroblasts are observed by the 25% stage. During early neurogenesis these neuroblasts generate their progeny through mechanisms similar to those that occur in the segmental ganglia; each neuroblast divides asymmetrically to produce a chain of ganglion mother cells, and each ganglion mother cell divides symmetrically to produce a pair of neurons. Approximately 130 mitotically active, large neuroblasts are found in each brain hemisphere at the 30- 45% stages. Through morphogenetic movements that occur between the 30–35% stages these neuroblasts become located in positions which are predictive of the major brain regions that they give rise to. Many of the brain neuroblasts can be identified as individuals based on their stereotyped position in the neurogenic array. Immunocytochemical experiments with antibodies against, engrailed, fasciclin I and TERM-1 show that brain neuroblasts can also be characterized by their expression of cell-specific molecular labels. These studies indicate that many features of the complex mature insect brain derive from a surprisingly simple and stereotyped set of neuronal precursor cells. Thus, many of the concepts and methods that have been used to study neurogenesis in the simpler segmental ganglia may also be applicable to the insect brai
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Zhao, Guoyan, and James B. Skeath. "The Sox-domain containing geneDichaete/fish-hookacts in concert withvndandindto regulate cell fate in theDrosophilaneuroectoderm." Development 129, no. 5 (March 1, 2002): 1165–74. http://dx.doi.org/10.1242/dev.129.5.1165.
Full textAbstract:
In the Drosophila embryonic central nervous system, neural stem cells, called neuroblasts, acquire fates in a position-specific manner. Recent work has identified a set of genes that functions along the dorsoventral axis to enable neuroblasts that develop in different dorsoventral domains to acquire distinct fates. These genes include the evolutionarily conserved transcription factors ventral nerve cord defective and intermediate neuroblasts defective, as well as the Drosophila EGF receptor. We show that the Sox-domain-containing gene Dichaete/fish-hook also plays a crucial role to pattern the neuroectoderm along the DV axis. Dichaete is expressed in the medial and intermediate columns of the neuroectoderm, and mutant analysis indicates that Dichaete regulates cell fate and neuroblast formation in these domains. Molecular epistasis tests, double mutant analysis and dosage-sensitive interactions demonstrate that during these processes, Dichaete functions in parallel with ventral nerve cord defective and intermediate neuroblasts defective, and downstream of EGF receptor signaling to mediate its effect on development. These results identify Dichaete as an important regulator of dorsoventral pattern in the neuroectoderm, and indicate that Dichaete acts in concert with ventral nerve cord defective and intermediate neuroblasts defective to regulate pattern and cell fate in the neuroectoderm.
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Nakamuta, Shinichi, Yu-Ting Yang, Chia-Lin Wang, Nicholas B. Gallo, Jia-Ray Yu, Yilin Tai, and Linda Van Aelst. "Dual role for DOCK7 in tangential migration of interneuron precursors in the postnatal forebrain." Journal of Cell Biology 216, no. 12 (October 31, 2017): 4313–30. http://dx.doi.org/10.1083/jcb.201704157.
Full textAbstract:
Throughout life, stem cells in the ventricular–subventricular zone generate neuroblasts that migrate via the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into local interneurons. Although progress has been made toward identifying extracellular factors that guide the migration of these cells, little is known about the intracellular mechanisms that govern the dynamic reshaping of the neuroblasts’ morphology required for their migration along the RMS. In this study, we identify DOCK7, a member of the DOCK180-family, as a molecule essential for tangential neuroblast migration in the postnatal mouse forebrain. DOCK7 regulates the migration of these cells by controlling both leading process (LP) extension and somal translocation via distinct pathways. It controls LP stability/growth via a Rac-dependent pathway, likely by modulating microtubule networks while also regulating F-actin remodeling at the cell rear to promote somal translocation via a previously unrecognized myosin phosphatase–RhoA–interacting protein-dependent pathway. The coordinated action of both pathways is required to ensure efficient neuroblast migration along the RMS.
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Booker, R., and J. W. Truman. "Octopod, a homeotic mutation of the moth Manduca sexta, influences the fate of identifiable pattern elements within the CNS." Development 105, no. 3 (March 1, 1989): 621–28. http://dx.doi.org/10.1242/dev.105.3.621.
Full textAbstract:
Octopod (Octo) is a mutation of the moth Manduca sexta, which results in the homeotic transformation of the ventral surface of the first (A1) and less often the second (A2) abdominal segments in the anterior direction. The extent of the transformation ranges from a slight deformation of the ventral cuticle, up to the formation of miniature thoracic legs on A1. The extent of the transformation is always less within A2 as compared to A1. A genetic analysis revealed that Octo is an autosomal mutation which shows incomplete dominance. The effect of this mutation on the central nervous system (CNS) was assessed by examining the distribution and fate of the postembryonic neuroblasts in the segmental ganglia of Octo larvae. In each of the thoracic ganglia of wild-type larvae, there is a set of 45–47 neuroblasts; a reduced but homologous array of 24 and 10 neuroblasts are found in A1 and A2, respectively. Ganglion A1 of Octo larvae had 1 to 6 supernumerary neuroblasts, and 20% of the A2 ganglia showed a single ectopic neuroblast. The supernumerary neuroblasts corresponded to identifiable neuroblasts normally found in more anterior ganglia. The Octo mutation also influenced the mitotic activity of stem cells normally present in A1. In this case, the neuroblasts generated a lineage of cells that were typical of a thoracic location rather than A1. These data demonstrate that homeotic mutations can influence the fate of identifiable pattern elements within the CNS of an insect.
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Kapur, R. P., C. Yost, and R. D. Palmiter. "Aggregation chimeras demonstrate that the primary defect responsible for aganglionic megacolon in lethal spotted mice is not neuroblast autonomous." Development 117, no. 3 (March 1, 1993): 993–99. http://dx.doi.org/10.1242/dev.117.3.993.
Full textAbstract:
The lethal spotted (ls) mouse has been used as a model for the human disorder Hirschsprung's disease, because as in the latter condition, ls/ls homozygotes are born without ganglion cells in their terminal colons and, without surgical intervention, die early as a consequence of intestinal obstruction. Previous studies have led to the conclusion that hereditary aganglionosis in ls/ls mice occurs because neural crest-derived enteric neuroblasts fail to colonize the distal large intestine during embryogenesis, perhaps due to a primary defect in non-neuroblastic mesenchyme rather than migrating neuroblasts themselves. In this investigation, the latter issue was addressed directly, in vivo, by comparing the distributions of ls/ls and wild-type neurons in aggregation chimeras. Expression of a transgene, D beta H-nlacZ, in enteric neurons derived from the vagal neural crest, was used as a marker for ls/ls enteric neurons in chimeric mice. In these animals, when greater than 20% of the cells were wild-type, the ls/ls phenotype was rescued; such mice were neither spotted nor aganglionic. In addition, these ‘rescued’ mice had mixtures of ls/ls and wild-type neurons throughout their gastrointestinal systems including distal rectum. In contrast, mice with smaller relative numbers of wild-type cells exhibited the classic ls/ls phenotype. The aganglionic terminal bowel of the latter mice contained neither ls/ls nor wild-type neurons. These results confirm that the primary defect in ls/ls embryos is not autonomous to enteric neuroblasts, but instead exists in the non-neuroblastic mesenchyme of the large intestine.
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Sriha, Jessica, Caroline Louis-Brennetot, Cécile Pierre-Eugène, Sylvain Baulande, Virginie Raynal, Amira Kramdi, Igor Adameyko, et al. "BET and CDK Inhibition Reveal Differences in the Proliferation Control of Sympathetic Ganglion Neuroblasts and Adrenal Chromaffin Cells." Cancers 14, no. 11 (June 1, 2022): 2755. http://dx.doi.org/10.3390/cancers14112755.
Full textAbstract:
Neuroblastoma arising from the adrenal differ from ganglionic neuroblastoma both genetically and clinically, with adrenal tumors being associated with a more severe prognosis. The different tumor properties may be linked to specific tumor founder cells in adrenal and sympathetic ganglia. To address this question, we first set up cultures of mouse sympathetic neuroblasts and adrenal chromaffin cells. These cultures were then treated with various proliferation inhibitors to identify lineage-specific responses. We show that neuroblast and chromaffin cell proliferation was affected by WNT, ALK, IGF1, and PRC2/EZH2 signaling inhibitors to a similar extent. However, differential effects were observed in response to bromodomain and extraterminal (BET) protein inhibitors (JQ1, GSK1324726A) and to the CDK-7 inhibitor THZ1, with BET inhibitors preferentially affecting chromaffin cells, and THZ1 preferentially affecting neuroblasts. The differential dependence of chromaffin cells and neuroblasts on BET and CDK signaling may indicate different mechanisms during tumor initiation in sympathetic ganglia and adrenal.
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Prokop, A., and G. M. Technau. "The origin of postembryonic neuroblasts in the ventral nerve cord of Drosophila melanogaster." Development 111, no. 1 (January 1, 1991): 79–88. http://dx.doi.org/10.1242/dev.111.1.79.
Full textAbstract:
Embryonic and postembryonic neuroblasts in the thoracic ventral nerve cord of Drosophila melanogaster have the same origin. We have traced the development of threefold-labelled single precursor cells from the early gastrula stage to late larval stages. The technique allows in the same individual monitoring of progeny cells at embryonic stages (in vivo) and differentially staining embryonic and postembryonic progeny within the resulting neural clone at late postembryonic stages. The analysis reveals that postembryonic cells always appear together with embryonic cells in one clone. Furthermore, BrdU labelling suggests that the embryonic neuroblast itself rather than one of its progeny resumes proliferation as a postembryonic neuroblast. A second type of clone consists of embryonic progeny only.
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Akter, Mariyam, Naoko Kaneko, Vicente Herranz-Pérez, Sayuri Nakamura, Hisashi Oishi, Jose Manuel García-Verdugo, and Kazunobu Sawamoto. "Dynamic Changes in the Neurogenic Potential in the Ventricular–Subventricular Zone of Common Marmoset during Postnatal Brain Development." Cerebral Cortex 30, no. 7 (February 28, 2020): 4092–109. http://dx.doi.org/10.1093/cercor/bhaa031.
Full textAbstract:
Abstract Even after birth, neuronal production continues in the ventricular–subventricular zone (V–SVZ) and hippocampus in many mammals. The immature new neurons (“neuroblasts”) migrate and then mature at their final destination. In humans, neuroblast production and migration toward the neocortex and the olfactory bulb (OB) occur actively only for a few months after birth and then sharply decline with age. However, the precise spatiotemporal profiles and fates of postnatally born neurons remain unclear due to methodological limitations. We previously found that common marmosets, small nonhuman primates, share many features of V–SVZ organization with humans. Here, using marmosets injected with thymidine analogue(s) during various postnatal periods, we demonstrated spatiotemporal changes in neurogenesis during development. V–SVZ progenitor proliferation and neuroblast migration toward the OB and neocortex sharply decreased by 4 months, most strikingly in a V–SVZ subregion from which neuroblasts migrated toward the neocortex. Postnatally born neurons matured within a few months in the OB and hippocampus but remained immature until 6 months in the neocortex. While neurogenic activity was sustained for a month after birth, the distribution and/or differentiation diversity was more restricted in 1-month-born cells than in the neonatal-born population. These findings shed light on distinctive features of postnatal neurogenesis in primates.
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Chen, Jiao, and Zhonghui Guan. "Function of Oncogene Mycn in Adult Neurogenesis and Oligodendrogenesis." Molecular Neurobiology 59, no. 1 (October 8, 2021): 77–92. http://dx.doi.org/10.1007/s12035-021-02584-7.
Full textAbstract:
AbstractHuman MYCN is an oncogene amplified in neuroblastoma and many other tumors. Both human MYCN and mouse Mycn genes are important in embryonic brain development, but their functions in adult healthy nerve system are completely unknown. Here, with Mycn-eGFP mice and quantitative RT-PCR, we found that Mycn was expressed in specific brain regions of young adult mice, including subventricular zone (SVZ), subgranular zone (SGZ), olfactory bulb (OB), subcallosal zone (SCZ), and corpus callosum (CC). With immunohistochemistry (IHC), we found that many Mycn-expressing cells expressed neuroblast marker doublecortin (DCX) and proliferation marker Ki67. With Dcx-creER and Mki67-creER mouse lines, we fate mapped Dcx-expressing neuroblasts and Mki67-expressing proliferation cells, along with deleting Mycn from these cells in adult mice. We found that knocking out Mycn from adult neuroblasts or proliferating cells significantly reduced cells in proliferation in SVZ, SGZ, OB, SCZ, and CC. We also demonstrated that the Mycn-deficient neuroblasts in SGZ matured quicker than wild-type neuroblasts, and that Mycn-deficient proliferating cells were more likely to survive in SVZ, SGZ, OB, SCZ, and CC compared to wild type. Thus, our results demonstrate that, in addition to causing tumors in the nervous system, oncogene Mycn has a crucial function in neurogenesis and oligodendrogenesis in adult healthy brain.
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Brody, Thomas, and Ward F. Odenwald. "Cellular diversity in the developing nervous system: a temporal view from Drosophila." Development 129, no. 16 (August 15, 2002): 3763–70. http://dx.doi.org/10.1242/dev.129.16.3763.
Full textAbstract:
This article considers the evidence for temporal transitions in CNS neural precursor cell gene expression during development. In Drosophila, five prospective competence states have so far been identified, characterized by the successive expression of Hb→Kr→Pdm→Cas→Gh in many, but not all, neuroblasts. In each temporal window of transcription factor expression, the neuroblast generates sublineages whose temporal identity is determined by the competence state of the neuroblast at the time of birth of the sublineage. Although similar regulatory programs have not yet been identified in mammals, candidate regulatory genes have been identified. Further investigation of the genetic programs that guide both invertebrate and vertebrate neural precursor cell lineage development will ultimately lead to an understanding of the molecular events that control neuronal diversity.
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Buescher, Marita, Fook Sion Hing, and William Chia. "Formation of neuroblasts in the embryonic central nervous system of Drosophila melanogaster is controlled by SoxNeuro." Development 129, no. 18 (September 15, 2002): 4193–203. http://dx.doi.org/10.1242/dev.129.18.4193.
Full textAbstract:
Sox proteins form a family of HMG-box transcription factors related to the mammalian testis determining factor SRY. Sox-mediated modulation of gene expression plays an important role in various developmental contexts. Drosophila SoxNeuro, a putative ortholog of the vertebrate Sox1, Sox2 and Sox3 proteins, is one of the earliest transcription factors to be expressed pan-neuroectodermally. We demonstrate that SoxNeuro is essential for the formation of the neural progenitor cells in central nervous system. We show that loss of function mutations of SoxNeuro are associated with a spatially restricted hypoplasia: neuroblast formation is severely affected in the lateral and intermediate regions of the central nervous system, whereas ventral neuroblast formation is almost normal. We present evidence that a requirement for SoxNeuro in ventral neuroblast formation is masked by a functional redundancy with Dichaete, a second Sox protein whose expression partially overlaps that of SoxNeuro. Genetic interactions of SoxNeuro and the dorsoventral patterning genes ventral nerve chord defective and intermediate neuroblasts defective underlie ventral and intermediate neuroblast formation. Finally, the expression of the Achaete-Scute gene complex suggests that SoxNeuro acts upstream and in parallel with the proneural genes.
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Ashraf, Shovon I., and Y. Tony Ip. "The Snail protein family regulates neuroblast expression of inscuteable and string, genes involved in asymmetry and cell division in Drosophila." Development 128, no. 23 (December 1, 2001): 4757–67. http://dx.doi.org/10.1242/dev.128.23.4757.
Full textAbstract:
Delaminated neuroblasts in Drosophila function as stem cells during embryonic central nervous system development. They go through repeated asymmetric divisions to generate multiple ganglion mother cells, which divide only once more to produce postmitotic neurons. Snail, a zinc-finger transcriptional repressor, is a pan-neural protein, based on its extensive expression in neuroblasts. Previous results have demonstrated that Snail and related proteins, Worniu and Escargot, have redundant and essential functions in the nervous system. We show that the Snail family of proteins control central nervous system development by regulating genes involved in asymmetry and cell division of neuroblasts. In mutant embryos that have the three genes deleted, the expression of inscuteable is significantly lowered, while the expression of other genes that participate in asymmetric division, including miranda, staufen and prospero, appears normal. The deletion mutants also have much reduced expression of string, suggesting that a key component that drives neuroblast cell division is abnormal. Consistent with the gene expression defects, the mutant embryos lose the asymmetric localization of prospero RNA in neuroblasts and lose the staining of Prospero protein that is normally present in ganglion mother cells. Simultaneous expression of inscuteable and string in the snail family deletion mutant efficiently restores Prospero expression in ganglion mother cells, demonstrating that the two genes are key targets of Snail in neuroblasts. Mutation of the dCtBP co-repressor interaction motifs in the Snail protein leads to reduction of the Snail function in central nervous system. These results suggest that the Snail family of proteins control both asymmetry and cell division of neuroblasts by activating, probably indirectly, the expression of inscuteable and string.
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Saini, Nidhi, and Heinrich Reichert. "Neural Stem Cells inDrosophila: Molecular Genetic Mechanisms Underlying Normal Neural Proliferation and Abnormal Brain Tumor Formation." Stem Cells International 2012 (2012): 1–10. http://dx.doi.org/10.1155/2012/486169.
Full textAbstract:
Neural stem cells inDrosophilaare currently one of the best model systems for understanding stem cell biology during normal development and during abnormal development of stem cell-derived brain tumors. InDrosophilabrain development, the proliferative activity of neural stem cells called neuroblasts gives rise to both the optic lobe and the central brain ganglia, and asymmetric cell divisions are key features of this proliferation. The molecular mechanisms that underlie the asymmetric cell divisions by which these neuroblasts self-renew and generate lineages of differentiating progeny have been studied extensively and involve two major protein complexes, the apical complex which maintains polarity and controls spindle orientation and the basal complex which is comprised of cell fate determinants and their adaptors that are segregated into the differentiating daughter cells during mitosis. Recent molecular genetic work has establishedDrosophilaneuroblasts as a model for neural stem cell-derived tumors in which perturbation of key molecular mechanisms that control neuroblast proliferation and the asymmetric segregation of cell fate determinants lead to brain tumor formation. Identification of novel candidate genes that control neuroblast self-renewal and differentiation as well as functional analysis of these genes in normal and tumorigenic conditions in a tissue-specific manner is now possible through genome-wide transgenic RNAi screens. These cellular and molecular findings inDrosophilaare likely to provide valuable genetic links for analyzing mammalian neural stem cells and tumor biology.
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Weigmann, K., and C. F. Lehner. "Cell fate specification by even-skipped expression in the Drosophila nervous system is coupled to cell cycle progression." Development 121, no. 11 (November 1, 1995): 3713–21. http://dx.doi.org/10.1242/dev.121.11.3713.
Full textAbstract:
The correct specification of defined neurons in the Drosophila central nervous system is dependent on even-skipped. During CNS development, even-skipped expression starts in the ganglion mother cell resulting from the first asymmetric division of neuroblast NB 1–1. This first division of NB 1–1 (and of the other early neuroblasts as well) is temporally controlled by the transcriptional regulation of string expression, which we have manipulated experimentally, even-skipped expression still occurs if the first neuroblast division is delayed, but not if the division is prohibited. Moreover, even-skipped expression is also dependent on progression through S phase which follows immediately after the first division. However, cytokinesis during the first NB division is not required for even-skipped expression as revealed by observations in pebble mutant embryos. Our results demonstrate therefore that even-skipped expression is coupled to cell cycle progression, presumably in order to prevent a premature activation of expression by a positive regulator which is produced already in the neuroblast during G2 and segregated asymmetrically into the ganglion mother cell during mitosis.
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Ou, Guangshuo, and Ronald D. Vale. "Molecular signatures of cell migration in C. elegans Q neuroblasts." Journal of Cell Biology 185, no. 1 (April 6, 2009): 77–85. http://dx.doi.org/10.1083/jcb.200812077.
Full textAbstract:
Metazoan cell movement has been studied extensively in vitro, but cell migration in living animals is much less well understood. In this report, we have studied the Caenorhabditis elegans Q neuroblast lineage during larval development, developing live animal imaging methods for following neuroblast migration with single cell resolution. We find that each of the Q descendants migrates at different speeds and for distinct distances. By quantitative green fluorescent protein imaging, we find that Q descendants that migrate faster and longer than their sisters up-regulate protein levels of MIG-2, a Rho family guanosine triphosphatase, and/or down-regulate INA-1, an integrin α subunit, during migration. We also show that Q neuroblasts bearing mutations in either MIG-2 or INA-1 migrate at reduced speeds. The migration defect of the mig-2 mutants, but not ina-1, appears to result from a lack of persistent polarization in the direction of cell migration. Thus, MIG-2 and INA-1 function distinctly to control Q neuroblast migration in living C. elegans.
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Connell, Marisa, Clemens Cabernard, Derek Ricketson, Chris Q. Doe, and Kenneth E. Prehoda. "Asymmetric cortical extension shifts cleavage furrow position in Drosophila neuroblasts." Molecular Biology of the Cell 22, no. 22 (November 15, 2011): 4220–26. http://dx.doi.org/10.1091/mbc.e11-02-0173.
Full textAbstract:
The cytokinetic cleavage furrow is typically positioned symmetrically relative to the cortical cell boundaries, but it can also be asymmetric. The mechanisms that control furrow site specification have been intensively studied, but how polar cortex movements influence ultimate furrow position remains poorly understood. We measured the position of the apical and the basal cortex in asymmetrically dividing Drosophila neuroblasts and observed preferential displacement of the apical cortex that becomes the larger daughter cell during anaphase, effectively shifting the cleavage furrow toward the smaller daughter cell. Asymmetric cortical extension is correlated with the presence of cortical myosin II, which is polarized in neuroblasts. Loss of myosin II asymmetry by perturbing heterotrimeric G-protein signaling results in symmetric extension and equal-sized daughter cells. We propose a model in which contraction-driven asymmetric polar extension of the neuroblast cortex during anaphase contributes to asymmetric furrow position and daughter cell size.
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Egger, Boris, James M. Chell, and Andrea H. Brand. "Insights into neural stem cell biology from flies." Philosophical Transactions of the Royal Society B: Biological Sciences 363, no. 1489 (February 19, 2007): 39–56. http://dx.doi.org/10.1098/rstb.2006.2011.
Full textAbstract:
Drosophila neuroblasts are similar to mammalian neural stem cells in their ability to self-renew and to produce many different types of neurons and glial cells. In the past two decades, great advances have been made in understanding the molecular mechanisms underlying embryonic neuroblast formation, the establishment of cell polarity and the temporal regulation of cell fate. It is now a challenge to connect, at the molecular level, the different cell biological events underlying the transition from neural stem cell maintenance to differentiation. Progress has also been made in understanding the later stages of development, when neuroblasts become mitotically inactive, or quiescent, and are then reactivated postembryonically to generate the neurons that make up the adult nervous system. The ability to manipulate the steps leading from quiescence to proliferation and from proliferation to differentiation will have a major impact on the treatment of neurological injury and neurodegenerative disease.
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DiCicco-Bloom, E., E. Townes-Anderson, and I. B. Black. "Neuroblast mitosis in dissociated culture: regulation and relationship to differentiation." Journal of Cell Biology 110, no. 6 (June 1, 1990): 2073–86. http://dx.doi.org/10.1083/jcb.110.6.2073.
Full textAbstract:
Although neuron generation is precisely regulated during ontogeny, little is known about underlying mechanisms. In addition, relationships between precursor proliferation and the apparent sequence of developmental processes, including cell migration, neurite elaboration, transmitter expression and synaptogenesis remain unknown. To address these issues, we used a fully defined neuronal cell culture system derived from embryonic rat sympathetic ganglia (DiCicco-Bloom, E., and I. B. Black. 1988. Proc. Natl. Acad. Sci. USA. 85:4066-4070) in which precursors enter the mitotic cycle. We now find that, in addition to synthesizing DNA, neuroblasts also underwent division in culture, allowing analysis of developmental relationships and mitotic regulation. Our observations indicate that mitotic neuroblasts expressed a wide array of neuron-specific characteristics including extension of neuritic processes with growth cones, elaboration of neurotransmitter enzyme, synthesis and transport of transmitter vesicles and organization of transmitter release sites. These data suggest that neuroblasts in the cell cycle may simultaneously differentiate. Consequently, the apparent sequence of ontogenetic processes is not an immutable, intrinsic neuronal program. How, then, are diverse developmental events coordinated? Our observations indicate that neuroblast mitosis is regulated by a small number of epigenetic factors, including insulin and EGF. Since these signals also influence other processes in developing neurons, epigenetic regulation normally may synchronize diverse ontogenetic events.
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Rolls, Melissa M., Roger Albertson, Hsin-Pei Shih, Cheng-Yu Lee, and Chris Q. Doe. "Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and epithelia." Journal of Cell Biology 163, no. 5 (December 1, 2003): 1089–98. http://dx.doi.org/10.1083/jcb.200306079.
Full textAbstract:
Cell polarity is essential for generating cell diversity and for the proper function of most differentiated cell types. In many organisms, cell polarity is regulated by the atypical protein kinase C (aPKC), Bazooka (Baz/Par3), and Par6 proteins. Here, we show that Drosophila aPKC zygotic null mutants survive to mid-larval stages, where they exhibit defects in neuroblast and epithelial cell polarity. Mutant neuroblasts lack apical localization of Par6 and Lgl, and fail to exclude Miranda from the apical cortex; yet, they show normal apical crescents of Baz/Par3, Pins, Inscuteable, and Discs large and normal spindle orientation. Mutant imaginal disc epithelia have defects in apical/basal cell polarity and tissue morphology. In addition, we show that aPKC mutants show reduced cell proliferation in both neuroblasts and epithelia, the opposite of the lethal giant larvae (lgl) tumor suppressor phenotype, and that reduced aPKC levels strongly suppress most lgl cell polarity and overproliferation phenotypes.
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Rehen, S. K., M. H. Varella, F. G. Freitas, M. O. Moraes, and R. Linden. "Contrasting effects of protein synthesis inhibition and of cyclic AMP on apoptosis in the developing retina." Development 122, no. 5 (May 1, 1996): 1439–48. http://dx.doi.org/10.1242/dev.122.5.1439.
Full textAbstract:
The role of protein synthesis in apoptosis was investigated in the retina of developing rats. In the neonatal retina, a ganglion cell layer, containing neurons with long, centrally projecting axons, is separated from an immature neuroblastic layer by a plexiform layer. This trilaminar pattern subsequently evolves to five alternating cell and plexiform layers that constitute the mature retina and a wave of programmed neuron death sweeps through the layers. Apoptosis due to axon damage was found in ganglion cells of retinal explants within 2 days in vitro and was prevented by inhibition of protein synthesis. Simultaneously, protein synthesis blockade induced apoptosis among the undamaged cells of the neuroblastic layer, which could be selectively prevented by an increase in intracellular cyclic AMP. Both the prevention and the induction of apoptosis among ganglion cells or neuroblastic cells, respectively, occurred after inhibition of protein synthesis in vivo. The results show the coexistence of two mechanisms of apoptosis within the organized retinal tissue. One mechanism is triggered in ganglion cells by direct damage and depends on the synthesis of proteins acting as positive modulators of apoptosis. A distinct, latent mechanism is found among immature neuroblasts and may be repressed by continuously synthesized negative modulators, or by an increase in intracellular cyclic AMP.
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Costine, Beth A., Symeon Missios, Sabrina R. Taylor, Declan McGuone, Colin M. Smith, Carter P. Dodge, Brent T. Harris, and Ann-Christine Duhaime. "The Subventricular Zone in the Immature Piglet Brain: Anatomy and Exodus of Neuroblasts into White Matter after Traumatic Brain Injury." Developmental Neuroscience 37, no. 2 (2015): 115–30. http://dx.doi.org/10.1159/000369091.
Full textAbstract:
Stimulation of postnatal neurogenesis in the subventricular zone (SVZ) and robust migration of neuroblasts to the lesion site in response to traumatic brain injury (TBI) is well established in rodent species; however, it is not yet known whether postnatal neurogenesis plays a role in repair after TBI in gyrencephalic species. Here we describe the anatomy of the SVZ in the piglet for the first time and initiate an investigation into the effect of TBI on the SVZ architecture and the number of neuroblasts in the white matter. Among all ages of immaturity examined the SVZ contained a dense mesh network of neurogenic precursor cells (doublecortin+) positioned directly adjacent to the ependymal cells (ventricular SVZ, Vsvz) and neuroblasts organized into chains that were distinct from the Vsvz (abventricular SVZ, Asvz). Though the architecture of the SVZ was similar among ages, the areas of Vsvz and Asvz neuroblast chains declined with age. At postnatal day (PND) 14 the white matter tracts have a tremendous number of individual neuroblasts. In our scaled cortical impact model, lesion size increased with age. Similarly, the response of the SVZ to injury was also age dependent. The younger age groups that sustained the proportionately smallest lesions had the largest SVZ areas, which further increased in response to injury. In piglets that were injured at 4 months of age and had the largest lesions, the SVZ did not increase in response to injury. Similar to humans, swine have abundant gyri and gyral white matter, providing a unique platform to study neuroblasts potentially migrating from the SVZ to the lesioned cortex along these white matter tracts. In piglets injured at PND 7, TBI did not increase the total number of neuroblasts in the white matter compared to uninjured piglets, but redistribution occurred with a greater number of neuroblasts in the white matter of the hemisphere ipsilateral to the injury compared to the contralateral hemisphere. At 7 days after injury, less than 1% of neuroblasts in the white matter were born in the 2 days following injury. These data show that the SVZ in the piglet shares many anatomical similarities with the SVZ in the human infant, and that TBI had only modest effects on the SVZ and the number of neuroblasts in the white matter. Piglets at an equivalent developmental stage to human infants were equipped with the largest SVZ and a tremendous number of neuroblasts in the white matter, which may be sufficient in lesion repair without the dramatic stimulation of neurogenic machinery. It has yet to be determined whether neurogenesis and migrating neuroblasts play a role in repair after TBI and/or whether an alteration of normal migration during active postnatal population of brain regions is beneficial in species with gyrencephalic brains.
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Harris, Kathryn P., and Ulrich Tepass. "Cdc42 and Par proteins stabilize dynamic adherens junctions in the Drosophila neuroectoderm through regulation of apical endocytosis." Journal of Cell Biology 183, no. 6 (December 8, 2008): 1129–43. http://dx.doi.org/10.1083/jcb.200807020.
Full textAbstract:
Cell rearrangements require dynamic changes in cell–cell contacts to maintain tissue integrity. We investigated the function of Cdc42 in maintaining adherens junctions (AJs) and apical polarity in the Drosophila melanogaster neuroectodermal epithelium. About one third of cells exit the epithelium through ingression and become neuroblasts. Cdc42-compromised embryos lost AJs in the neuroectoderm during neuroblast ingression. In contrast, when neuroblast formation was suppressed, AJs were maintained despite the loss of Cdc42 function. Loss of Cdc42 function caused an increase in the endocytotic uptake of apical proteins, including apical polarity factors such as Crumbs, which are required for AJ stability. In addition, Cdc42 has a second function in regulating endocytotic trafficking, as it is required for the progression of apical cargo from the early to the late endosome. The Par complex acts as an effector for Cdc42 in controlling the endocytosis of apical proteins. This study reveals functional interactions between apical polarity proteins and endocytosis that are critical for stabilizing dynamic basolateral AJs.
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Ceccamea, Alberto, Francesco Carlei, Carlo Dominici, Manuel A. Castello, Davide Lomanto, Carlo A. Cappelli, and Emanuele Lezoche. "Correlation between Tyrosine Hydroxylase Immunoreactive Cells in Tumors and Urinary Catecholamine Output in Neuroblastoma Patients." Tumori Journal 72, no. 5 (October 1986): 451–57. http://dx.doi.org/10.1177/030089168607200501.
Full textAbstract:
The results of an immunocytochemical evaluation of tyrosine hydroxylase (TH) immunoreactivity in 30 neuroblastic tumors of infancy are reported. Although no correlations could be found between the immunoreactive pattern and the site of origin or the staging of the tumor, a positive relationship between the urinary catecholamine output and the density of TH-immunoreactive cells could be established. TH was mostly localized on the cytoplasm of the differentiating neuroblasts, whereas immature elements were rarely positive. Moreover, 2 stage IVS cases did not contain any TH immunoreactivity. The possible significance of this finding in the investigation of this form of neuroblastoma, which has a peculiar biological behavior, is considered.
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Wang, Zhaolu, Nuno Andrade, Malene Torp, Somsak Wattananit, Andreas Arvidsson, Zaal Kokaia, Jesper Roland Jørgensen, and Olle Lindvall. "Meteorin is a Chemokinetic Factor in Neuroblast Migration and Promotes Stroke-Induced Striatal Neurogenesis." Journal of Cerebral Blood Flow & Metabolism 32, no. 2 (November 2, 2011): 387–98. http://dx.doi.org/10.1038/jcbfm.2011.156.
Full textAbstract:
Ischemic stroke affecting the adult brain causes increased progenitor proliferation in the subventricular zone (SVZ) and generation of neuroblasts, which migrate into the damaged striatum and differentiate to mature neurons. Meteorin (METRN), a newly discovered neurotrophic factor, is highly expressed in neural progenitor cells and immature neurons during development, suggesting that it may be involved in neurogenesis. Here, we show that METRN promotes migration of neuroblasts from SVZ explants of postnatal rats and stroke-subjected adult rats via a chemokinetic mechanism, and reduces N-methyl-d-asparate-induced apoptotic cell death in SVZ cells in vitro. Stroke induced by middle cerebral artery occlusion upregulates the expression of endogenous METRN in cells with neuronal phenotype in striatum. Recombinant METRN infused into the stroke-damaged brain stimulates cell proliferation in SVZ, promotes neuroblast migration, and increases the number of immature and mature neurons in the ischemic striatum. Our findings identify METRN as a new factor promoting neurogenesis both in vitro and in vivo by multiple mechanisms. Further work will be needed to translate METRN's actions on endogenous neurogenesis into improved recovery after stroke.
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Honda, H., M. Tanemura, and A. Yoshida. "Estimation of neuroblast numbers in insect neurogenesis using the lateral inhibition hypothesis of cell differentiation." Development 110, no. 4 (December 1, 1990): 1349–52. http://dx.doi.org/10.1242/dev.110.4.1349.
Full textAbstract:
Cells in the neurogenic region of an insect ectoderm have two alternative fates, making neurons or epidermis. The fates seem to be determined through a laterally inhibitory interaction among cells. That is, initially homogeneous cells are all competent to differentiate into neuroblasts. Once a cell has differentiated as a neuroblast, it inhibits its immediate neighbors from following this pathway. The differentiation process is simulated by a digital computer in a planar array of polygonal domains similar to a cell pattern. We find that the number of cells differentiating as neuronal precursors in insect neurogenesis is that expected under the hypothesis of lateral inhibition of cell differentiation between immediate neighbors.