Zeitschriftenartikel: „Sensory organs precursors“

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Giangrande, A. „Proneural genes influence gliogenesis in Drosophila“. Development 121, Nr. 2 (01.02.1995): 429–38. http://dx.doi.org/10.1242/dev.121.2.429.

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Fly glial cells in the wing peripheral nervous system of Drosophila melanogaster originate from underlying epithelial cells. Two findings indicate that gliogenesis is closely associated with neurogenesis. First, it only occurs in regions that also give rise to sensory organs. Second, in mutants that induce the development of ectopic sensory organs glial cells develop at new positions. These findings prompted a genetic analysis to establish whether glial and sensory organ differentiation depend on the same genes. Loss of function mutations of the achaete-scute complex lead to a significant reduction of sensory bristles and glial cells. Genes within the complex affect gliogenesis with different strength and display some functional redundancy. Thus, neurogenesis and gliogenesis share the same genetic pathway. Despite these similarities, however, the mechanism of action of the achaete-scute complex seems to be different in the two processes. Neural precursors express products of the complex, therefore the role of these genes on neurogenesis is direct. However, markers specific to glial cells do not colocalize with products of the achaete-scute complex, showing that the complex affects gliogenesis indirectly. These observations lead to the hypothesis that gliogenesis is induced by the presence of sensory organ cells, either the precursor or its progeny.

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Van De Bor, V., R. Walther und A. Giangrande. „Some fly sensory organs are gliogenic and require glide/gcm in a precursor that divides symmetrically and produces glial cells“. Development 127, Nr. 17 (01.09.2000): 3735–43. http://dx.doi.org/10.1242/dev.127.17.3735.

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In flies, the choice between neuronal and glial fates depends on the asymmetric division of multipotent precursors, the neuroglioblast of the central nervous system and the IIb precursor of the sensory organ lineage. In the central nervous system, the choice between the two fates requires asymmetric distribution of the glial cell deficient/glial cell missing (glide/gcm) RNA in the neuroglioblast. Preferential accumulation of the transcript in one of the daughter cells results in the activation of the glial fate in that cell, which becomes a glial precursor. Here we show that glide/gcm is necessary to induce glial differentiation in the peripheral nervous system. We also present evidence that glide/gcm RNA is not necessary to induce the fate choice in the peripheral multipotent precursor. Indeed, glide/gcm RNA and protein are first detected in one daughter of IIb but not in IIb itself. Thus, glide/gcm is required in both central and peripheral glial cells, but its regulation is context dependent. Strikingly, we have found that only subsets of sensory organs are gliogenic and express glide/gcm. The ability to produce glial cells depends on fixed, lineage related, cues and not on stochastic decisions. Finally, we show that after glide/gcm expression has ceased, the IIb daughter migrates and divides symmetrically to produce several mature glial cells. Thus, the glide/gcm-expressing cell, also called the fifth cell of the sensory organ, is indeed a glial precursor. This is the first reported case of symmetric division in the sensory organ lineage. These data indicate that the organization of the fly peripheral nervous system is more complex than previously thought.

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Hartenstein, V., und J. W. Posakony. „Development of adult sensilla on the wing and notum of Drosophila melanogaster“. Development 107, Nr. 2 (01.10.1989): 389–405. http://dx.doi.org/10.1242/dev.107.2.389.

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We have investigated the temporal pattern of appearance, cell lineage, and cytodifferentiation of selected sensory organs (sensilla) of adult Drosophila. This analysis was facilitated by the discovery that the monoclonal antibody 22C10 labels not only the neuron of the developing sensillum organ, but the accessory cells as well. The precursors of the macrochaetes and the recurved (chemosensory) bristles of the wing margin divide around and shortly after puparium formation, while those of the microchaetes and the stout and slender (mechanosensory) bristles of the wing margin divide between 9 h and 18 h after puparium formation (apf). The onset of sensillum differentiation follows the terminal precursor division within a few hours. Four of the cells in an individual microchaete organ are clonally related: A single first-order precursor cell divides to produce two second-order precursors; one of these divides into the neuron and thecogen cell, the other into the trichogen cell and tormogen cell. Along the anterior wing margin, two rounds of division generate the cells of the mechanosensory sensilla; here, no strict clonal relationship seems to exist between the cells of an individual sensillum. At the time of sensillum precursor division, many other, non-sensillum-producing cells within the notum and wing proliferate as well. This mitotic activity follows a spatially non-random pattern.

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Reddy, G. V., und V. Rodrigues. „Sibling cell fate in the Drosophila adult external sense organ lineage is specified by prospero function, which is regulated by Numb and Notch“. Development 126, Nr. 10 (15.05.1999): 2083–92. http://dx.doi.org/10.1242/dev.126.10.2083.

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Specification of cell fate in the adult sensory organs is known to be dependent on intrinsic and extrinsic signals. We show that the homeodomain transcription factor Prospero (Pros) acts as an intrinsic signal for the specification of cell fates within the mechanosensory lineage. The sensory organ precursors divide to give rise to two secondary progenitors - PIIa and PIIb. Pros is expressed in PIIb, which gives rise to the neuron and thecogen cells. Loss of Pros function affects the identity of PIIb and neurons fail to differentiate. Pros misexpression is sufficient for the transformation of PIIa to PIIb fate. The expression of Pros in the normal PIIb cell appears to be regulated by Notch signaling.

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Vervoort, M., D. J. Merritt, A. Ghysen und C. Dambly-Chaudiere. „Genetic basis of the formation and identity of type I and type II neurons in Drosophila embryos“. Development 124, Nr. 14 (15.07.1997): 2819–28. http://dx.doi.org/10.1242/dev.124.14.2819.

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The embryonic peripheral nervous system of Drosophila contains two main types of sensory neurons: type I neurons, which innervate external sense organs and chordotonal organs, and type II multidendritic neurons. Here, we analyse the origin of the difference between type I and type II in the case of the neurons that depend on the proneural genes of the achaete-scute complex (ASC). We show that, in Notch- embryos, the type I neurons are missing while type II neurons are produced in excess, indicating that the type I/type II choice relies on Notch-mediated cell communication. In contrast, both type I and type II neurons are absent in numb- embryos and after ubiquitous expression of tramtrack, indicating that the activity of numb and the absence of tramtrack are required to produce both external sense organ and multidendritic neural fates. The analysis of string- embryos reveals that when the precursors are unable to divide they differentiate mostly into type II neurons, indicating that the type II is the default neuronal fate. We also report a new mutant phenotype where the ASC-dependent neurons are converted into type II neurons, providing evidence for the existence of one or more genes required for maintaining the alternative (type I) fate. Our results suggest that the same mechanism of type I/type II specification may operate at a late step of the ASC-dependent lineages, when multidendritic neurons arise as siblings of the external sense organ neurons and, at an early step, when other multidendritic neurons precursors arise as siblings of external sense organ precursors.

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Okabe, M., und H. Okano. „Two-step induction of chordotonal organ precursors in Drosophila embryogenesis“. Development 124, Nr. 5 (01.03.1997): 1045–53. http://dx.doi.org/10.1242/dev.124.5.1045.

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The chordotonal (Ch) organ, an internal stretch receptor located in the subepidermal layer, is one of the major sensory organs in the peripheral nervous system of Drosophila melanogaster. Although the cell lineage of the Ch organ has been well characterized in many studies, the determination machinery of Ch organ precursor cells (COPs) remains largely unresolved. Here we report that the rhomboid (rho) gene and the activity of the Drosophila EGF receptor (DER) signaling pathway are necessary to induce specifically three of the eight COPs in an embryonic abdominal hemisegment. The cell-lineage analysis of COPs using the yeast flpase (flp/FRT) method indicated that each of the eight COPs originated from an individual undifferentiated ectodermal cell. The eight COPs in each abdominal hemisegment seemed to be determined by a two-phase induction: first, five COPs are determined by the action of the proneural gene atonal and neurogenic genes. Subsequently, these five COPs start to express the rho gene, and rho activates the DER-signaling pathway in neighboring cells and induces argos expression. Three of these argos-expressing cells differentiate into the three remaining COPs and they prevent neighboring cells from becoming extra COPs.

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Blochlinger, K., L. Y. Jan und Y. N. Jan. „Postembryonic patterns of expression of cut, a locus regulating sensory organ identity in Drosophila“. Development 117, Nr. 2 (01.02.1993): 441–50. http://dx.doi.org/10.1242/dev.117.2.441.

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The cut locus is both necessary and sufficient to specify the identity of a class of sensory organs in Drosophila embryos. It is also expressed in and required for the development of a number of other embryonic tissues, such as the central nervous system, the Malpighian tubules and the tracheal system. We here describe the expression of cut in the precursors of adult sensory organs. We also show that cut is expressed in cells of the prospective wing margin and correlate the wing margin phenotype caused by two cut mutations with altered cut expression patterns. Finally, we observe cut-expressing cells in other adult tissues, including Malpighian tubules, muscles, the central nervous system and ovarian follicle cells.

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zur Lage, P., und A. P. Jarman. „Antagonism of EGFR and notch signalling in the reiterative recruitment of Drosophila adult chordotonal sense organ precursors“. Development 126, Nr. 14 (15.07.1999): 3149–57. http://dx.doi.org/10.1242/dev.126.14.3149.

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The selection of Drosophila melanogaster sense organ precursors (SOPs) for sensory bristles is a progressive process: each neural equivalence group is transiently defined by the expression of proneural genes (proneural cluster), and neural fate is refined to single cells by Notch-Delta lateral inhibitory signalling between the cells. Unlike sensory bristles, SOPs of chordotonal (stretch receptor) sense organs are tightly clustered. Here we show that for one large adult chordotonal SOP array, clustering results from the progressive accumulation of a large number of SOPs from a persistent proneural cluster. This is achieved by a novel interplay of inductive epidermal growth factor-receptor (EGFR) and competitive Notch signals. EGFR acts in opposition to Notch signalling in two ways: it promotes continuous SOP recruitment despite lateral inhibition, and it attenuates the effect of lateral inhibition on the proneural cluster equivalence group, thus maintaining the persistent proneural cluster. SOP recruitment is reiterative because the inductive signal comes from previously recruited SOPs.

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Brugmann, Samantha A., und Sally A. Moody. „Induction and specification of the vertebrate ectodermal placodes: precursors of the cranial sensory organs“. Biology of the Cell 97, Nr. 5 (Mai 2005): 303–19. http://dx.doi.org/10.1042/bc20040515.

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Beisel, Kirk W., Yesha Wang-Lundberg, Adel Maklad und Bernd Fritzsch. „Development and evolution of the vestibular sensory apparatus of the mammalian ear“. Journal of Vestibular Research 15, Nr. 5-6 (01.11.2005): 225–41. http://dx.doi.org/10.3233/ves-2005-155-601.

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Herein, we will review molecular aspects of vestibular ear development and present them in the context of evolutionary changes and hair cell regeneration. Several genes guide the development of anterior and posterior canals. Although some of these genes are also important for horizontal canal development, this canal strongly depends on a single gene, Otx1. Otx1 also governs the segregation of saccule and utricle. Several genes are essential for otoconia and cupula formation, but protein interactions necessary to form and maintain otoconia or a cupula are not yet understood. Nerve fiber guidance to specific vestibular end-organs is predominantly mediated by diffusible neurotrophic factors that work even in the absence of differentiated hair cells. Neurotrophins, in particular Bdnf, are the most crucial attractive factor released by hair cells. If Bdnf is misexpressed, fibers can be redirected away from hair cells. Hair cell differentiation is mediated by Atoh1. However, Atoh1 may not initiate hair cell precursor formation. Resolving the role of Atoh1 in postmitotic hair cell precursors is crucial for future attempts in hair cell regeneration. Additional analyses are needed before gene therapy can help regenerate hair cells, restore otoconia, and reconnect sensory epithelia to the brain.

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Van De Bor, Véronique, Pascal Heitzler, Sophie Leger, Charles Plessy und Angela Giangrande. „Precocious Expression of the Glide/Gcm Glial-Promoting Factor in Drosophila Induces Neurogenesis“. Genetics 160, Nr. 3 (01.03.2002): 1095–106. http://dx.doi.org/10.1093/genetics/160.3.1095.

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Abstract Neurons and glial cells depend on similar developmental pathways and often originate from common precursors; however, the differentiation of one or the other cell type depends on the activation of cell-specific pathways. In Drosophila, the differentiation of glial cells depends on a transcription factor, Glide/Gcm. This glial-promoting factor is both necessary and sufficient to induce the central and peripheral glial fates at the expense of the neuronal fate. In a screen for mutations affecting the adult peripheral nervous system, we have found a dominant mutation inducing supernumerary sensory organs. Surprisingly, this mutation is allelic to glide/gcm and induces precocious glide/gcm expression, which, in turn, activates the proneural genes. As a consequence, sensory organs are induced. Thus, temporal misregulation of the Glide/Gcm glial-promoting factor reveals a novel potential for this cell fate determinant. At the molecular level, this implies unpredicted features of the glide/gcm pathway. These findings also emphasize the requirement for both spatial and temporal glide/gcm regulation to achieve proper cell specification within the nervous system.

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Roegiers, Fabrice, Lily Yeh Jan und Yuh Nung Jan. „Regulation of Membrane Localization of Sanpodo by lethal giant larvae and neuralized in Asymmetrically Dividing Cells of Drosophila Sensory Organs“. Molecular Biology of the Cell 16, Nr. 8 (August 2005): 3480–87. http://dx.doi.org/10.1091/mbc.e05-03-0177.

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In Drosophila, asymmetric division occurs during proliferation of neural precursors of the central and peripheral nervous system (PNS), where a membrane-associated protein, Numb, is asymmetrically localized during cell division and is segregated to one of the two daughter cells (the pIIb cell) after mitosis. numb has been shown genetically to function as an antagonist of Notch signaling and also as a negative regulator of the membrane localization of Sanpodo, a four-pass transmembrane protein required for Notch signaling during asymmetric cell division in the CNS. Previously, we identified lethal giant larvae (lgl) as a gene required for numb-mediated inhibition of Notch in the adult PNS. In this study we show that Sanpodo is expressed in asymmetrically dividing precursor cells of the PNS and that Sanpodo internalization in the pIIb cell is dependent cytoskeletally associated Lgl. Lgl specifically regulates internalization of Sanpodo, likely through endocytosis, but is not required for the endocytosis Delta, which is a required step in the Notch-mediated cell fate decision during asymmetric cell division. Conversely, the E3 ubiquitin ligase neuralized is required for both Delta endocytosis and the internalization of Sanpodo. This study identifies a hitherto unreported role for Lgl as a regulator of Sanpodo during asymmetric cell division in the adult PNS.

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Wülbeck, Corinna, und Pat Simpson. „The expression of pannier and achaete-scute homologues in a mosquito suggests an ancient role of pannier as a selector gene in the regulation of the dorsal body pattern“. Development 129, Nr. 16 (15.08.2002): 3861–71. http://dx.doi.org/10.1242/dev.129.16.3861.

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The Drosophila gene pannier (pnr) has recently been assigned to a new class of selector genes (Calleja, M., Herranz, H., Estella, C., Casal, J., Lawrence, P., Simpson, P. and Morata, G. (2000). Development 127, 3971-3980; (Mann, R. S. and Morata, G. (2000). Annu. Rev. Cell Dev. Biol. 16, 243-271). It specifies pattern in the dorsal body. On the dorsal notum it is expressed in a broad medial domain and directly regulates transcription of the achaete-scute (ac-sc) genes driving their expression in small discrete clusters within this domain at the sites of each future bristle. This spatial resolution is achieved through modulation of Pnr activity by specific co-factors and by a number of discrete cis-regulatory enhancers in the ac-sc gene complex. We have isolated homologues of pnr and ac-sc in Anopheles gambiae, a basal species of Diptera that diverged from Drosophila melanogaster (Dm) about 200 million years ago, and examined their expression patterns. We found that an ac-sc homologue of Anopheles, Ag-ASH, is expressed on the dorsal medial notum at the sites where sensory organs emerge in several domains that are identical to those of the pnr homologue, Ag-pnr. This suggests that activation of Ag-ASH by Ag-Pnr has been conserved. Indeed, when expressed in Drosophila, Ag-pnr is able to mimic the effects of ectopic expression of Dm-pnr and induce ectopic bristles. These results are discussed in the context of the gene duplication events and the acquisition of a modular promoter, that may have occurred at different times in the lineage leading to derived species such as Drosophila. The bristle pattern of Anopheles correlates in a novel fashion with the expression domains of Ag-pnr/Ag-ASH. While precursors for the sensory scales can arise anywhere within the expression domains, bristle precursors arise exclusively along the borders. This points to the existence of specific positional information along the borders, and suggests that Ag-pnr specifies pattern in the medial, dorsal notum, as in Drosophila, but via a different mechanism.

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Nevoa, Jessica Coraiola, Jose Manuel Latorre-Estivalis, Fabiano Sviatopolk-Mirsky Pais, Newmar Pinto Marliére, Gabriel da Rocha Fernandes, Marcelo Gustavo Lorenzo und Alessandra Aparecida Guarneri. „Global characterization of gene expression in the brain of starved immature Rhodnius prolixus“. PLOS ONE 18, Nr. 3 (03.03.2023): e0282490. http://dx.doi.org/10.1371/journal.pone.0282490.

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Background Rhodnius prolixus is a vector of Chagas disease and has become a model organism to study physiology, behavior, and pathogen interaction. The publication of its genome allowed initiating a process of comparative characterization of the gene expression profiles of diverse organs exposed to varying conditions. Brain processes control the expression of behavior and, as such, mediate immediate adjustment to a changing environment, allowing organisms to maximize their chances to survive and reproduce. The expression of fundamental behavioral processes like feeding requires fine control in triatomines because they obtain their blood meals from potential predators. Therefore, the characterization of gene expression profiles of key components modulating behavior in brain processes, like those of neuropeptide precursors and their receptors, seems fundamental. Here we study global gene expression profiles in the brain of starved R. prolixus fifth instar nymphs by means of RNA sequencing (RNA-Seq). Results The expression of neuromodulatory genes such as those of precursors of neuropeptides, neurohormones, and their receptors; as well as the enzymes involved in the biosynthesis and processing of neuropeptides and biogenic amines were fully characterized. Other important gene targets such as neurotransmitter receptors, nuclear receptors, clock genes, sensory receptors, and takeouts genes were identified and their gene expression analyzed. Conclusion We propose that the set of neuromodulatory-related genes highly expressed in the brain of starved R. prolixus nymphs deserves functional characterization to allow the subsequent development of tools targeting them for bug control. As the brain is a complex structure that presents functionally specialized areas, future studies should focus on characterizing gene expression profiles in target areas, e.g. mushroom bodies, to complement our current knowledge.

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Martínez, C., J. Modolell und J. Garrell. „Regulation of the proneural gene achaete by helix-loop-helix proteins“. Molecular and Cellular Biology 13, Nr. 6 (Juni 1993): 3514–21. http://dx.doi.org/10.1128/mcb.13.6.3514-3521.1993.

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The Achaete (Ac) protein, a transcriptional regulator of the basic-helix-loop-helix (bHLH) type, confers upon ectodermal cells the ability to become neural precursors. Its temporally and spatially regulated expression, together with that of the related Scute (Sc) protein, helps define the pattern of Drosophila melanogaster sensory organs. We have examined the transcriptional control of the ac gene and shown, using in vivo assays, that several E-boxes, putative interacting sites for bHLH proteins, present in the ac promoter are most important for ac regulation. They most likely mediate ac self-stimulation and sc trans-activation. We also demonstrate that ac transcription is negatively regulated in vivo by the gene extramacrochaetae (emc) in a manner dependent on Ac and Sc products. emc encodes an HLH protein that lacks the basic region and presumably antagonizes Ac and Sc function by sequestering these proteins in complexes unable to interact with DNA. Our results strongly support the model of negative regulation of emc on ac and sc transcription through titration of their products. As currently thought, this seems accomplished by heterodimerization via the HLH domain, because an amino acid substitution in this region abolishes the emc antagonistic effect both in vitro and in vivo.

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Martínez, C., J. Modolell und J. Garrell. „Regulation of the proneural gene achaete by helix-loop-helix proteins.“ Molecular and Cellular Biology 13, Nr. 6 (Juni 1993): 3514–21. http://dx.doi.org/10.1128/mcb.13.6.3514.

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The Achaete (Ac) protein, a transcriptional regulator of the basic-helix-loop-helix (bHLH) type, confers upon ectodermal cells the ability to become neural precursors. Its temporally and spatially regulated expression, together with that of the related Scute (Sc) protein, helps define the pattern of Drosophila melanogaster sensory organs. We have examined the transcriptional control of the ac gene and shown, using in vivo assays, that several E-boxes, putative interacting sites for bHLH proteins, present in the ac promoter are most important for ac regulation. They most likely mediate ac self-stimulation and sc trans-activation. We also demonstrate that ac transcription is negatively regulated in vivo by the gene extramacrochaetae (emc) in a manner dependent on Ac and Sc products. emc encodes an HLH protein that lacks the basic region and presumably antagonizes Ac and Sc function by sequestering these proteins in complexes unable to interact with DNA. Our results strongly support the model of negative regulation of emc on ac and sc transcription through titration of their products. As currently thought, this seems accomplished by heterodimerization via the HLH domain, because an amino acid substitution in this region abolishes the emc antagonistic effect both in vitro and in vivo.

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Brewster, R., und R. Bodmer. „Origin and specification of type II sensory neurons in Drosophila“. Development 121, Nr. 9 (01.09.1995): 2923–36. http://dx.doi.org/10.1242/dev.121.9.2923.

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The peripheral nervous system (PNS) of Drosophila is a preferred model for studying the genetic basis of neurogenesis because its simple and stereotyped pattern makes it ideal for mutant analysis. Type I sensory organs, the external (bristle-type) sensory organs (es) and the internal (stretch-receptive) chordotonal organs (ch), have been postulated to derive from individual ectodermal precursor cells that undergo a stereotyped pattern of cell division. Little is known about the origin and specification of type II sensory neurons, the multiple dendritic (md) neurons. Using the flp/FRT recombinase system from yeast, we have determined that a subset of md neurons derives from es organ lineages, another subset derives from ch organ lineages and a third subset is unrelated to sensory organs. We also provide evidence that the genes, numb and cut, are both required for the proper differentiation of md neurons.

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Martin-Bermudo, M. D., C. Martinez, A. Rodriguez und F. Jimenez. „Distribution and function of the lethal of scute gene product during early neurogenesis in Drosophila“. Development 113, Nr. 2 (01.10.1991): 445–54. http://dx.doi.org/10.1242/dev.113.2.445.

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Genes of the achaete-scute complex (ASC) participate in the formation of the central nervous system in the Drosophila embryo. Previous genetic analyses have indicated that lethal of scute (l'sc) is the most important gene of the complex in that process. We have obtained antibodies against the l'sc protein to study the expression of the gene during early neurogenesis. The protein is found in groups of embryonic neuroectodermal cells, analogous to the proneural clusters that precede the appearance of precursors of peripheral sensory organs in imaginal epithelia. The groups appear in different regions of the neuroectoderm, accompanying the three successive waves of neuroblast segregation. Most neuroblasts delaminate from these clusters and express position-specific levels of l'sc protein. No significant differences have been found between the distribution of l'sc RNA and protein. Phenotypic analysis of a l'sc deficiency has shown that the gene is required for neuroblast commitment, although this requirement is less widespread than the domain of l'sc expression, suggesting a high degree of redundancy in the function of genes that participate in the process of neuroblast segregation. The ASC genes have been postulated to play a role in the control of NB identity, revealed by the generation of a defined lineage of identifiable neurons. However, our study in l'sc mutants of the expression of fushi tarazu, engrailed, and even-skipped, used as markers of neuronal identity, has not provided evidence to support this hypothesis.

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Abdelilah-Seyfried, Salim, Yee-Ming Chan, Chaoyang Zeng, Nicholas J. Justice, Susan Younger-Shepherd, Linda E. Sharp, Sandra Barbel, Sarah A. Meadows, Lily Yeh Jan und Yuh Nung Jan. „A Gain-of-Function Screen for Genes That Affect the Development of the Drosophila Adult External Sensory Organ“. Genetics 155, Nr. 2 (01.06.2000): 733–52. http://dx.doi.org/10.1093/genetics/155.2.733.

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Abstract The Drosophila adult external sensory organ, comprising a neuron and its support cells, is derived from a single precursor cell via several asymmetric cell divisions. To identify molecules involved in sensory organ development, we conducted a tissue-specific gain-of-function screen. We screened 2293 independent P-element lines established by P. Rørth and identified 105 lines, carrying insertions at 78 distinct loci, that produced misexpression phenotypes with changes in number, fate, or morphology of cells of the adult external sensory organ. On the basis of the gain-of-function phenotypes of both internal and external support cells, we subdivided the candidate lines into three classes. The first class (52 lines, 40 loci) exhibits partial or complete loss of adult external sensory organs. The second class (38 lines, 28 loci) is associated with increased numbers of entire adult external sensory organs or subsets of sensory organ cells. The third class (15 lines, 10 loci) results in potential cell fate transformations. Genetic and molecular characterization of these candidate lines reveals that some loci identified in this screen correspond to genes known to function in the formation of the peripheral nervous system, such as big brain, extra macrochaetae, and numb. Also emerging from the screen are a large group of previously uncharacterized genes and several known genes that have not yet been implicated in the development of the peripheral nervous system.

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Tanumihardja, Esther, Wouter Olthuis und Albert van den Berg. „Ruthenium Oxide Nanorods as Potentiometric pH Sensor for Organs-On-Chip Purposes“. Sensors 18, Nr. 9 (01.09.2018): 2901. http://dx.doi.org/10.3390/s18092901.

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A ruthenium oxide (RuOx) sensor for potentiometric pH sensing is currently being developed for organs-on-chip purposes. The sensor was fabricated from a Ru(OH)3 precursor, resulting in RuOx nanorods after heating. An open-circuit potential of the RuOx electrode showed a near-Nernstian response of −58.05 mV/pH, with good selectivity against potentially interfering ions (lithium, sulfate, chloride, and calcium ions). The preconditioned electrode (stored in liquid) had a long-term drift of −0.8 mV/h, and its response rate was less than 2 s. Sensitivity to oxygen was observed at an order of magnitude lower than other reported metal-oxide pH sensors. Together with miniaturizability, the RuOx pH sensor proves to be a suitable pH sensor for organs-on-chip studies.

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Pi, Haiwei, Hui-Ju Wu und Cheng-Ting Chien. „A dual function ofphyllopodinDrosophilaexternal sensory organ development: cell fate specification of sensory organ precursor and its progeny“. Development 128, Nr. 14 (15.07.2001): 2699–710. http://dx.doi.org/10.1242/dev.128.14.2699.

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During Drosophila external sensory organ development, one sensory organ precursor (SOP) arises from a proneural cluster, and undergoes asymmetrical cell divisions to produce an external sensory (es) organ made up of different types of daughter cells. We show that phyllopod (phyl), previously identified to be essential for R7 photoreceptor differentiation, is required in two stages of es organ development: the formation of SOP cells and cell fate specification of SOP progeny. Loss-of-function mutations in phyl result in failure of SOP formation, which leads to missing bristles in adult flies. At a later stage of es organ development, phyl mutations cause the first cell division of the SOP lineage to generate two identical daughters, leading to the fate transformation of neurons and sheath cells to hair cells and socket cells. Conversely, misexpression of phyl promotes ectopic SOP formation, and causes opposite fate transformation in SOP daughter cells. Thus, phyl functions as a genetic switch in specifying the fate of the SOP cells and their progeny. We further show that seven in absentia (sina), another gene required for R7 cell fate differentiation, is also involved in es organ development. Genetic interactions among phyl, sina and tramtrack (ttk) suggest that phyl and sina function in bristle development by antagonizing ttk activity, and ttk acts downstream of phyl. It has been shown previously that Notch (N) mutations induce formation of supernumerary SOP cells, and transformation from hair and socket cells to neurons. We further demonstrate that phyl acts epistatically to N. phyl is expressed specifically in SOP cells and other neural precursors, and its mRNA level is negatively regulated by N signaling. Thus, these analyses demonstrate that phyl acts downstream of N signaling in controlling cell fates in es organ development.

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Nagel, Stefan, Corinna Meyer, Maren Kaufmann, Roderick MacLeod und Hans G. Drexler. „Aberrant Expression of Homeobox Gene SIX1 in Hodgkin Lymphoma“. Blood 126, Nr. 23 (03.12.2015): 2638. http://dx.doi.org/10.1182/blood.v126.23.2638.2638.

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Abstract In Hodgkin lymphoma (HL) we recently identified deregulated expression of homeobox gene MSX1 which physiologically controls development of the embryonal neural plate border region. This region forms the neural crest and placodes which in turn give rise to fundamental structures and functions of the head including jaw and sensory organs. Here, we examined in HL another homeobox gene, SIX1, an additional regulator of this embryonal region mediating differentiation of placodal precursors. In silico data (GSE12453) show aberrantly activated SIX1 in 12 % of HL patient samples, indicating a pathological role in a subset of this malignancy. In addition, SIX1 expression was detected in HL cell lines which then were used as models to reveal regulators and target genes of this basic developmental factor. Cytogenetics and quantitative genomic PCR revealed copy number gains of the SIX1 locus at chromosomal band 14q23 correlating with enhanced expression while chromosomal translocations were absent. Moreover, comparative expression profiling data and pertinent gene modulation experiments indicated that the WNT-signalling pathway activates and transcription factor MEF2C suppresses SIX1 expression. MAPK7/ERK5 and HDAC9 phosphorylate and deacetylate MEF2C, respectively, boosting or constraining its inhibitory capacity. MEF2C, MAPK7 and HDAC9 show aberrant expression levels in both HL cell lines and patient samples, collectively restricting the inhibitory activity of MEF2C. Genes encoding the transcription factors GATA2, GATA3, MSX1 and SPIB - all basic lymphoid regulators - were identified as targets of SIX1 in HL, contributing to deregulated B-cell differentiation in this malignancy. In addition, cofactors EYA1 and TLE4 contrastingly mediated activation and suppression of SIX1 target gene expression, respectively. Thus, the protein domain interfaces may represent therapeutic targets in SIX1-positive HL subsets to prevent cofactor interactions and subsequent target gene regulation. Collectively, our data reveal a gene regulatory network where SIX1 centrally deregulates lymphoid differentiation. Additionally, our data strengthen the emerging concordance of lymphopoiesis/lymphomagenesis and the neural plate border region ontogeny. Disclosures No relevant conflicts of interest to declare.

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Orgogozo, V., F. Schweisguth und Y. Bellaiche. „Lineage, cell polarity and inscuteable function in the peripheral nervous system of the Drosophila embryo“. Development 128, Nr. 5 (01.03.2001): 631–43. http://dx.doi.org/10.1242/dev.128.5.631.

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The stereotyped pattern of the Drosophila embryonic peripheral nervous system (PNS) makes it an ideal system to use to identify mutations affecting cell polarity during asymmetric cell division. However, the characterisation of such mutations requires a detailed description of the polarity of the asymmetric divisions in the sensory organ lineages. We describe the pattern of cell divisions generating the vp1-vp4a mono-innervated external sense (es) organs. Each sensory organ precursor (SOP) cell follows a series of four asymmetric cell divisions that generate the four es organs cells (the socket, shaft, sheath cells and the es neurone) together with one multidendritic (md) neurone. This lineage is distinct from any of the previously proposed es lineages. Strikingly, the stereotyped pattern of cell divisions in this lineage is identical to those described for the embryonic chordotonal organ lineage and for the adult thoracic bristle lineage. Our analysis reveals that the vp2-vp4a SOP cells divide with a planar polarity to generate a dorsal pIIa cell and a ventral pIIb cell. The pIIb cell next divides with an apical-basal polarity to generate a basal daughter cell that differentiates as an md neurone. We found that Inscuteable specifically accumulated at the apical pole of the dividing pIIb cell and regulated the polarity of the pIIb division. This study establishes for the first time the function of Inscuteable in the PNS, and provides the basis for studying the mechanisms controlling planar and apical-basal cell polarities in the embryonic sensory organ lineages.

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Gho, M., M. Lecourtois, G. Geraud, J. W. Posakony und F. Schweisguth. „Subcellular localization of Suppressor of Hairless in Drosophila sense organ cells during Notch signalling“. Development 122, Nr. 6 (01.06.1996): 1673–82. http://dx.doi.org/10.1242/dev.122.6.1673.

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During imaginal development of Drosophila, Suppressor of Hairless [Su(H)], an evolutionarily conserved transcription factor that mediates intracellular signalling by the Notch (N) receptor, controls successive alternative cell fate decisions leading to the differentiation of multicellular sensory organs. We describe here the distribution of the Su(H) protein in the wing disc epithelium throughout development of adult sense organs. Su(H) was found to be evenly distributed in the nuclei of all imaginal disc cells during sensory organ precursor cells selection. Thus differential expression and/or subcellular localization of Su(H) is not essential for its function. Soon after division of the pIIa secondary precursor cell, Su(H) specifically accumulates in the nucleus of the future socket cell. At the onset of differentiation of the socket cell, Su(H) is also detected in the cytoplasm. In this differentiating cell, N and deltex participate in the cytoplasmic retention of Su(H). Still, Su(H) does not colocalize with N at the apical-lateral membranes. These observations suggest that N regulates in an indirect manner the cytoplasmic localization of Su(H) in the socket cell. Finally, the pIIb, shaft and socket cells are found to adopt invariant positions along the anteroposterior axis of the notum. This raises the possibility that tissue-polarity biases these N-mediated cell fate choices.

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de Celis, J. F., R. Barrio und F. C. Kafatos. „Regulation of the spalt/spalt-related gene complex and its function during sensory organ development in the Drosophila thorax“. Development 126, Nr. 12 (15.06.1999): 2653–62. http://dx.doi.org/10.1242/dev.126.12.2653.

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The nuclear proteins Spalt and Spalt-related belong to a conserved family of transcriptional regulators characterised by the presence of double zinc-finger domains. In the wing, they are regulated by the secreted protein Decapentaplegic and participate in the positioning of the wing veins. Here, we identify regulatory regions in the spalt/spalt-related gene complex that direct expression in the wing disc. The regulatory sequences are organised in independent modules, each of them responsible for expression in particular domains of the wing imaginal disc. In the thorax, spalt and spalt-related are expressed in a restricted domain that includes most proneural clusters of the developing sensory organs in the notum, and are regulated by the signalling molecules Wingless, Decapentaplegic and Hedgehog. We find that spalt/spalt-related participate in the development of sensory organs in the thorax, mainly in the positioning of specific proneural clusters. Later, the expression of at least spalt is eliminated from the sensory organ precursor cells and this is a requisite for the differentiation of these cells. We postulate that spalt and spalt-related belong to a category of transcriptional regulators that subdivide the thorax into expression domains (prepattern) required for the localised activation of proneural genes.

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Golubyatnikov, Vladimir P., Tatyana A. Bukharina und Dagmara P. Furman. „A model study of the morphogenesis of D. melanogaster mechanoreceptors: The central regulatory circuit“. Journal of Bioinformatics and Computational Biology 13, Nr. 01 (Februar 2015): 1540006. http://dx.doi.org/10.1142/s0219720015400065.

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Macrochaetes (large bristles) are sensor organs of the Drosophila peripheral nervous system with a function of mechanoreceptors. An adult mechanoreceptor comprises four specialized cells: shaft (trichogen), socket (tormogen), neuron, and glial cell (thecogen). All these cells originate from a single cell, the so-called sensor organ precursor (SOP) cell. Separation of the SOP cell from the encompassing cells of the imaginal disc initiates a multistage process of sensory organ development. A characteristic feature of the SOP cell is the highest amount of the proneural proteins AS-C as compared with the encompassing ectodermal cells. The accumulation of proneural proteins and maintenance of their amount in the SOP cell at a necessary level is provided by the gene network with the achaete–scute gene complex (AS-C) as its key component. The activity of this complex is controlled by the central regulatory circuit (CRC). The CRC comprises the genes hairy, senseless (sens), charlatan (chn), scratch (scrt), daughterless (da), extramacrochaete (emc), and groucho (gro), coding for the transcription factors involved in the system of direct links and feedbacks and implementation of activation–repression relationships between the CRC components. The gene phyllopod (phyl), involved in degradation of the AS-C proteins, is also associated with the CRC functioning. In this paper, we propose a mathematical model for the CRC functioning as a regulator of the amount of proneural AS-C proteins in the SOP cell taking into account their degradation. The modeling has demonstrated that a change in the amount of proneural proteins in the SOP cell is stepwise rather than strictly monotonic. This prediction can be tested experimentally.

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Barad, Omer, Eran Hornstein und Naama Barkai. „Robust selection of sensory organ precursors by the Notch–Delta pathway“. Current Opinion in Cell Biology 23, Nr. 6 (Dezember 2011): 663–67. http://dx.doi.org/10.1016/j.ceb.2011.09.005.

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Buffin, Eulalie, und Michel Gho. „Laser Microdissection of Sensory Organ Precursor Cells of Drosophila Microchaetes“. PLoS ONE 5, Nr. 2 (19.02.2010): e9285. http://dx.doi.org/10.1371/journal.pone.0009285.

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Schweisguth, F., und J. W. Posakony. „Antagonistic activities of Suppressor of Hairless and Hairless control alternative cell fates in the Drosophila adult epidermis“. Development 120, Nr. 6 (01.06.1994): 1433–41. http://dx.doi.org/10.1242/dev.120.6.1433.

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Successive alternative cell fate choices in the imaginal disc epithelium lead to the differentiation of a relatively invariant pattern of multicellular adult sensory organs in Drosophila. We show here that the activity of Suppressor of Hairless is required for both the sensory organ precursor (SOP) versus epidermal cell fate decision, and for the trichogen (shaft) versus tormogen (socket) cell fate choice. Complete loss of Suppressor of Hairless function causes most proneural cluster cells to accumulate high levels of the achaete and Delta proteins and to adopt the SOP fate. Late or partial reduction in Suppressor of Hairless activity leads to the apparent transformation of the tormogen (socket) cell into a second trichogen (shaft) cell, producing a ‘double shaft’ phenotype. We find that overexpression of Suppressor of Hairless has the opposite phenotypic effects. SOP determination is prevented by an early excess of Suppressor of Hairless activity, while at a later stage, the trichogen (shaft) cell is transformed into a second tormogen (socket) cell, resulting in ‘double socket’ bristles. We conclude that, for two different cell fate decisions in adult sensory organ development, decreasing or increasing the level of Suppressor of Hairless function confers mutant phenotypes that closely resemble those associated with gain and loss of Hairless activity, respectively. These results, along with the intermediate SOP phenotype observed in Suppressor of Hairless; Hairless double mutant imaginal discs, suggest that the two genes act antagonistically to commit imaginal disc cells stably to alternative fates.

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Bettler, Donald, Stephanie Pearson und Barry Yedvobnick. „The Nuclear Protein Encoded by the Drosophila Neurogenic Gene mastermind Is Widely Expressed and Associates With Specific Chromosomal Regions“. Genetics 143, Nr. 2 (01.06.1996): 859–75. http://dx.doi.org/10.1093/genetics/143.2.859.

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Abstract The Drosophila neurogenic loci encode a diverse group of proteins that comprise an inhibitory signal transduction pathway. The pathway is used throughout development in numerous contexts. We have examined the distribution of the neurogenic locus mastermind protein (Mam). Mam is expressed through all germlayers during early embryogenesis, including ectodermal precursors to both neuroblasts and epidermoblasts. Mam is subsequently down-regulated within the nervous system and then reexpressed. It persists in the nervous system through late embryogenesis and postembryonically. Mam is ubiquitously expressed in wing and leg imaginal discs and is not down-regulated in sensory organ precursor cells of the wing margin or notum. In the eye disc, Mam shows most prominent expression posterior to the morphogenetic furrow. Expression of the protein during oogenesis appears limited to follicle cells. Immunohistochemical detection of Mam on polytene chromosomes revealed binding at >100 sites. Chromosome colocalization studies with RNA polymerase and the groucho corepressor protein implicate Mam in transcriptional regulation.

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Li, Y., F. Wang, J. A. Lee und F. B. Gao. „MicroRNA-9a ensures the precise specification of sensory organ precursors in Drosophila“. Genes & Development 20, Nr. 20 (15.10.2006): 2793–805. http://dx.doi.org/10.1101/gad.1466306.

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Kaspar, Markus, Markus Schneider, William Chia und Thomas Klein. „Klumpfuss is involved in the determination of sensory organ precursors in Drosophila“. Developmental Biology 324, Nr. 2 (Dezember 2008): 177–91. http://dx.doi.org/10.1016/j.ydbio.2008.08.031.

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Wang, S., S. Younger-Shepherd, L. Y. Jan und Y. N. Jan. „Only a subset of the binary cell fate decisions mediated by Numb/Notch signaling in Drosophila sensory organ lineage requires Suppressor of Hairless“. Development 124, Nr. 22 (15.11.1997): 4435–46. http://dx.doi.org/10.1242/dev.124.22.4435.

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In Drosophila, an adult external sensory organ (bristle) consists of four distinct cells which arise from a sensory organ precursor cell via two rounds of asymmetric divisions. The sensory organ precursor cell first divides to generate two secondary precursor cells, IIa and IIb. The IIa cell then divides to produce the hair cell and the socket cell. Shortly after, the IIb cell divides to generate the neuron and the sheath cell. The membrane-associated protein Numb has been shown to be required for the first two asymmetric divisions. We now report that a new hypomorphic numb mutant not only displays a double-socket phenotype, due to a hair cell to socket cell transformation, but also a double-sheath phenotype, due to a neuron to sheath cell transformation. This provides direct evidence that numb functions in the neuron/sheath cell lineage as well. Those results, together with our observation from immunofluorescence analysis that Numb forms a crescent in the dividing IIa and IIb cells suggest that asymmetric localization of Numb is important for the cell fate determination in all three asymmetric cell divisions in the sensory organ lineage. Interestingly, we found that in the hair/socket cell lineage but not the neuron/sheath cell lineage, a Suppressor of Hairless mutation acts as a dominant suppressor of numb mutations whereas Hairless mutations act as enhancers of numb. Moreover, epistasis analysis indicates that Suppressor of Hairless acts downstream of numb, and results from in vitro binding analysis suggest that the genetic interaction between numb and Hairless may occur through direct protein-protein interaction. These studies reveal that Suppressor of Hairless is required for only a subset of the asymmetric divisions that depend on the function of numb and Notch.

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Jafar-Nejad, H. „Senseless acts as a binary switch during sensory organ precursor selection“. Genes & Development 17, Nr. 23 (01.12.2003): 2966–78. http://dx.doi.org/10.1101/gad.1122403.

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Cotton, Mathieu, Najate Benhra und Roland Le Borgne. „Numb Inhibits the Recycling of Sanpodo in Drosophila Sensory Organ Precursor“. Current Biology 23, Nr. 7 (April 2013): 581–87. http://dx.doi.org/10.1016/j.cub.2013.02.020.

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Heitzler, P., M. Bourouis, L. Ruel, C. Carteret und P. Simpson. „Genes of the Enhancer of split and achaete-scute complexes are required for a regulatory loop between Notch and Delta during lateral signalling in Drosophila“. Development 122, Nr. 1 (01.01.1996): 161–71. http://dx.doi.org/10.1242/dev.122.1.161.

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Like the neuroblasts of the central nervous system, sensory organ precursors of the peripheral nervous system of the Drosophila thorax arise as single spaced cells. However, groups of cells initially have neural potential as visualized by the expression of the proneural genes achaete and scute. A class of genes, known as the ‘neurogenic genes’, function to restrict the proportion of cells that differentiate as sensory organ precursors. They mediate cell communication between the competent cells by means of an inhibitory signal, Delta, that is transduced through the Notch receptor and results in a cessation of achaete-scute activity. Here we show that mutation of either the bHLH-encoding genes of the Enhancer of split complex (E(spl)-C) or groucho, like Notch or Delta mutants, cause an overproduction of sensory organ precursors at the expense of epidermis. The mutant cells behave antonomously suggesting that the corresponding gene products are required for reception of the inhibitory signal. Epistasis experiments place both E(spl)-C bHLH-encoding genes and groucho downstream of Notch and upstream of achaete and scute, consistent with the idea that they are part of the Notch signalling cascade. Since all competent cells produce both the receptor and its ligand, it was postulated that Notch and Delta are linked within each cell by a feedback loop. We show, that, like mutant Notch cells, cells mutant for E(spl)-C bHLH-encoding genes or groucho inhibit neighbouring wild-type cells causing them to adopt the epidermal fate. This inhibition requires the genes of the achaete-scute complex (AS-C) which must therefore regulate the signal Delta. Thus there is a regulatory loop between Notch and Delta that is under the transcriptional control of the E(spl)-C and AS-C genes.

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Lu, Bingwei, Tadao Usui, Tadashi Uemura, Lily Jan und Yuh-Nung Jan. „Flamingo controls the planar polarity of sensory bristles and asymmetric division of sensory organ precursors in Drosophila“. Current Biology 9, Nr. 21 (November 1999): 1247—S1. http://dx.doi.org/10.1016/s0960-9822(99)80505-3.

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Hsu, Chao-Ping, Pei-Hsuan Lee, Ching-Wei Chang und Cheng-Tsung Lee. „Constructing quantitative models from qualitative mutant phenotypes: preferences in selecting sensory organ precursors“. Bioinformatics 22, Nr. 11 (07.03.2006): 1375–82. http://dx.doi.org/10.1093/bioinformatics/btl082.

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Shiomi, K., M. Takeichi, Y. Nishida, Y. Nishi und T. Uemura. „Alternative cell fate choice induced by low-level expression of a regulator of protein phosphatase 2A in the Drosophila peripheral nervous system“. Development 120, Nr. 6 (01.06.1994): 1591–99. http://dx.doi.org/10.1242/dev.120.6.1591.

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The Drosophila gene twins encodes the regulatory B subunit of type 2A protein phosphatase. Here we report that its partial loss-of-function mutations caused abnormal morphogenesis in the adult peripheral nervous system. In wild-type flies, the mechanoreceptor, one major class of sensory organs, is composed of four specialized cells (one neuron and three accessory cells) that are derived from a single precursor cell. The hypomorphic twins mutations did not block division of this precursor, but most likely altered cell fate in this lineage to produce only accessory cells that form sensory structures. Stepwise reductions of twins protein enhanced this transformation. In these mutants, another regulatory subunit, A, and the catalytic subunit, C, of the phosphatase were expressed at normal levels. Therefore, the modulation of the phosphatase activity by the B subunit appears to be crucial for specification of neural cell identity.

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Bang, A. G., V. Hartenstein und J. W. Posakony. „Hairless is required for the development of adult sensory organ precursor cells in Drosophila“. Development 111, Nr. 1 (01.01.1991): 89–104. http://dx.doi.org/10.1242/dev.111.1.89.

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Reduction of the wild-type activity of the gene Hairless (H) results in two major phenotypic effects on the mechanosensory bristles of adult Drosophila. Bristles are either ‘lost’ (i.e. the shaft and socket fail to appear) or they exhibit a ‘double socket’ phenotype, in which the shaft is apparently transformed into a second socket. Analysis of the phenotypes conferred by a series of H mutant genotypes demonstrates (1) that different sensilla exhibit different patterns of response to decreasing levels of H+ function, and (2) that the ‘bristle loss’ phenotype results from greater loss of H+ function than the ‘double socket’ phenotype. The systematic study of H allelic combinations enabled us to identify genotypes that reliably produce specific mutant defects in particular positions on the bodies of adult flies. This permitted us to investigate the cellular development of sensilla in these same positions in larvae and pupae and thereby establish the developmental basis for the mutant phenotypes. We have found that H is required for at least two steps of adult sensillum development. In positions where ‘double socket’ microchaetes appear on the notum of H mutant flies, sensillum precursor cells are present in the developing pupa and divide normally, but their progeny adopt an aberrant spatial arrangement and fail to differentiate correctly. In regions of the notum exhibiting ‘bristle loss’ in adult H mutants, we were unable at the appropriate stages of development to detect sensillum-specific cell types, the precursor cell divisions that generate them, or the primary precursor cells themselves. Thus, the H ‘bristle loss’ phenotype appears to reflect a very early defect in sensillum development, namely the failure to specify and/or execute the sensory organ precursor cell fate. This finding indicates that H is one of a small number of identified genes for which the loss-of-function phenotype is the failure of sensillum precursor cell development.

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Zine, A., T. R. Van De Water und F. de Ribaupierre. „Notch signaling regulates the pattern of auditory hair cell differentiation in mammals“. Development 127, Nr. 15 (01.08.2000): 3373–83. http://dx.doi.org/10.1242/dev.127.15.3373.

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The development of the mammalian cochlea is an example of patterning in the peripheral nervous system. Sensory hair cells and supporting cells in the cochlea differentiate via regional and cell fate specification. The Notch signaling components shows both distinct and overlapping expression patterns of Notch1 receptor and its ligands Jagged1 (Jag1) and Jagged2 (Jag2) in the developing auditory epithelium of the rat. On embryonic day 16 (E16), many precursor cells within the Kolliker's organ immunostained for the presence of both Notch1 and Jag1, while the area of hair cell precursors did not express either Notch1 and Jag1. During initial events of hair cell differentiation between E18 and birth, Notch1 and Jag1 expression predominated in supporting cells and Jag2 in nascent hair cells. Early after birth, Jag2 expression decreased in hair cells while the pattern of Notch1 expression now included both supporting cells and hair cells. We show that the normal pattern of hair cell differentiation is disrupted by alteration of Notch signaling. A decrease of either Notch1 or Jag1 expression by antisense oligonucleotides in cultures of the developing sensory epithelium resulted in an increase in the number of hair cells. Our data suggest that the Notch1 signaling pathway is involved in a complex interplay between the consequences of different ligand-Notch1 combinations during cochlear morphogenesis and the phases of hair cell differentiation.

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Fan, Jianguo, Li Jia, Yan Li, Seham Ebrahim, Helen May-Simera, Alynda Wood, Robert J. Morell et al. „Maturation arrest in early postnatal sensory receptors by deletion of the miR-183/96/182 cluster in mouse“. Proceedings of the National Academy of Sciences 114, Nr. 21 (08.05.2017): E4271—E4280. http://dx.doi.org/10.1073/pnas.1619442114.

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The polycistronic miR-183/96/182 cluster is preferentially and abundantly expressed in terminally differentiating sensory epithelia. To clarify its roles in the terminal differentiation of sensory receptors in vivo, we deleted the entire gene cluster in mouse germline through homologous recombination. The miR-183/96/182 null mice display impairment of the visual, auditory, vestibular, and olfactory systems, attributable to profound defects in sensory receptor terminal differentiation. Maturation of sensory receptor precursors is delayed, and they never attain a fully differentiated state. In the retina, delay in up-regulation of key photoreceptor genes underlies delayed outer segment elongation and possibly mispositioning of cone nuclei in the retina. Incomplete maturation of photoreceptors is followed shortly afterward by early-onset degeneration. Cell biologic and transcriptome analyses implicate dysregulation of ciliogenesis, nuclear translocation, and an epigenetic mechanism that may control timing of terminal differentiation in developing photoreceptors. In both the organ of Corti and the vestibular organ, impaired terminal differentiation manifests as immature stereocilia and kinocilia on the apical surface of hair cells. Our study thus establishes a dedicated role of the miR-183/96/182 cluster in driving the terminal differentiation of multiple sensory receptor cells.

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Witt, Lorraine M., Lisa M. Gutzwiller, Amy L. Gresser, David Li-Kroeger, Tiffany A. Cook und Brian Gebelein. „Atonal, Senseless, and Abdominal-A regulate rhomboid enhancer activity in abdominal sensory organ precursors“. Developmental Biology 344, Nr. 2 (August 2010): 1060–70. http://dx.doi.org/10.1016/j.ydbio.2010.05.011.

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Gallicchio, Lorenzo, Sam Griffiths-Jones und Matthew Ronshaugen. „Single-cell visualization of mir-9a and Senseless co-expression during Drosophila melanogaster embryonic and larval peripheral nervous system development“. G3 Genes|Genomes|Genetics 11, Nr. 1 (22.12.2020): 1–11. http://dx.doi.org/10.1093/g3journal/jkaa010.

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Abstract The Drosophila melanogaster peripheral nervous system (PNS) comprises the sensory organs that allow the fly to detect environmental factors such as temperature and pressure. PNS development is a highly specified process where each sensilla originates from a single sensory organ precursor (SOP) cell. One of the major genetic orchestrators of PNS development is Senseless, which encodes a zinc finger transcription factor (Sens). Sens is both necessary and sufficient for SOP differentiation. Senseless expression and SOP number are regulated by the microRNA miR-9a. However, the reciprocal dynamics of Senseless and miR-9a are still obscure. By coupling single-molecule FISH with immunofluorescence, we are able to visualize transcription of the mir-9a locus and expression of Sens simultaneously. During embryogenesis, we show that the expression of mir-9a in SOP cells is rapidly lost as Senseless expression increases. However, this mutually exclusive expression pattern is not observed in the third instar imaginal wing disc, where some Senseless-expressing cells show active sites of mir-9a transcription. These data challenge and extend previous models of Senseless regulation and show complex co-expression dynamics between mir-9a and Senseless. The differences in this dynamic relationship between embryonic and larval PNS development suggest a possible switch in miR-9a function. Our work brings single-cell resolution to the understanding of dynamic regulation of PNS development by Senseless and miR-9a.

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Van Doren, M., H. M. Ellis und J. W. Posakony. „The Drosophila extramacrochaetae protein antagonizes sequence-specific DNA binding by daughterless/achaete-scute protein complexes“. Development 113, Nr. 1 (01.09.1991): 245–55. http://dx.doi.org/10.1242/dev.113.1.245.

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In Drosophila, a group of regulatory proteins of the helix-loop-helix (HLH) class play an essential role in conferring upon cells in the developing adult epidermis the competence to give rise to sensory organs. Proteins encoded by the daughterless (da) gene and three genes of the achaete-scute complex (AS-C) act positively in the determination of the sensory organ precursor cell fate, while the extramacrochaetae (emc) and hairy (h) gene products act as negative regulators. In the region upstream of the achaete gene of the AS-C, we have identified three ‘E box’ consensus sequences that are bound specifically in vitro by hetero-oligomeric complexes consisting of the da protein and an AS-C protein. We have used this DNA-binding activity to investigate the biochemical basis of the negative regulatory function of emc. Under the conditions of our experiments, the emc protein, but not the h protein, is able to antagonize specifically the in vitro DNA-binding activity of da/AS-C and putative da/da protein complexes. We interpret these results as follows: the heterodimerization capacity of the emc protein (conferred by its HLH domain) allows it to act in vivo as a competitive inhibitor of the formation of functional DNA-binding protein complexes by the da and AS-C proteins, thereby reducing the effective level of their transcriptional regulatory activity within the cell.

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Roegiers, Fabrice, Susan Younger-Shepherd, Lily Yeh Jan und Yuh Nung Jan. „Two types of asymmetric divisions in the Drosophila sensory organ precursor cell lineage“. Nature Cell Biology 3, Nr. 1 (06.12.2000): 58–67. http://dx.doi.org/10.1038/35050568.

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Couturier, Lydie, Khalil Mazouni, Fred Bernard, Charlotte Besson, Elodie Reynaud und François Schweisguth. „Regulation of cortical stability by RhoGEF3 in mitotic Sensory Organ Precursor cells inDrosophila“. Biology Open 6, Nr. 12 (03.11.2017): 1851–60. http://dx.doi.org/10.1242/bio.026641.

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He, Qianyu, Tianlan Hou, Xiaochun Fan, Shunxin Wang, Yanhong Wang und Shanshan Chen. „Juvenile hormone suppresses sensory organ precursor determination to block Drosophila adult abdomen morphogenesis“. Insect Biochemistry and Molecular Biology 157 (Juni 2023): 103957. http://dx.doi.org/10.1016/j.ibmb.2023.103957.

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Alexianu, Marilena, und Andrei Dan. „Amyloid neuropathy“. Romanian Journal of Neurology 8, Nr. 4 (31.12.2009): 178–84. http://dx.doi.org/10.37897/rjn.2009.4.5.

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Amyloidosis is the name given to a group of diseases characterized by the extracellular deposition of insoluble amyloid fibrils in different tissues and organs like kidneys, heart, liver, skin, nerves etc. Clinical manifestations of amyloidosis are determined by the amyloid precursor protein type, by the tissue containing amyloid deposits, and by the quantity of stored amyloid. We present here the data of a patient with sensory polyneuropathy, orthostatic hypotension, nephritic syndrome and benign IgG monoclonal gammopathy, in which we diagnosed amyloid neuropathy.

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Lyman, D. F., und B. Yedvobnick. „Drosophila Notch receptor activity suppresses Hairless function during adult external sensory organ development.“ Genetics 141, Nr. 4 (01.12.1995): 1491–505. http://dx.doi.org/10.1093/genetics/141.4.1491.

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Abstract The neurogenic Notch locus of Drosophila encodes a receptor necessary for cell fate decisions within equivalence groups, such as proneural clusters. Specification of alternate fates within clusters results from inhibitory communication among cells having comparable neural fate potential. Genetically, Hairless (H) acts as an antagonist of most neurogenic genes and may insulate neural precursor cells from inhibition. H function is required for commitment to the bristle sensory organ precursor (SOP) cell fate and for daughter cell fates. Using Notch gain-of-function alleles and conditional expression of an activated Notch transgene, we show that enhanced signaling produces H-like loss-of-function phenotypes by suppressing bristle SOP cell specification or by causing an H-like transformation of sensillum daughter cell fates. Furthermore, adults carrying Notch gain of function and H alleles exhibit synergistic enhancement of mutant phenotypes. Over-expression of an H+ transgene product suppressed virtually all phenotypes generated by Notch gain-of-function genotypes. Phenotypes resulting from over-expression of the H+ transgene were blocked by the Notch gain-of-function products, indicating a balance between Notch and H activity. The results suggest that H insulates SOP cells from inhibition and indicate that H activity is suppressed by Notch signaling.

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