Dissertations / Theses: 'Neural precursor'

1

Piao, Jinghua. "Human neural precursor cells in spinal cord repair /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-288-0/.

Full text

APA, Harvard, Vancouver, ISO, and other styles

2

Heins, Nico. "Intrinsic fate determinants of neural and multipotent CNS precursor cells." Diss., lmu, 2005. http://nbn-resolving.de/urn:nbn:de:bvb:19-45202.

Full text

APA, Harvard, Vancouver, ISO, and other styles

3

Aarum, Johan. "Interactions between mouse CNS cells: microglia and neural precursor cells /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-120-2/.

Full text

APA, Harvard, Vancouver, ISO, and other styles

4

Callard, N. A. L. "Time-lapse studies of neural precursor cell divisions in vitro." Thesis, University College London (University of London), 2008. http://discovery.ucl.ac.uk/1444131/.

Full text

Abstract:

The entire adult central nervous system (CNS) derives from an initially small population of apparently homogeneous neuroepithelial precursor cells (NEPs) which produce specific differentiating cell types in a highly organised fashion with respect to both the time and place at which they are generated. A unifying phenomenon throughout the CNS is that neurons are always generated before glia. To better understand what mechanisms might be involved, the dynamics of precursor lineages need to be described. Here, single NEPs from the murine dorsal embryonic neocortex were cultured at clonal density and filmed using time-lapse microscopy to monitor their divisions over time. The progeny they gave rise to were identified by immunocytochemical methods and expression of the oligodendrocyte lineage-affiliated transcription factor, olig2 was directly observed by using a transgenic mouse that expressed enhanced green fluorescent protein (EGFP) in olig2-expressing cells. (The transgenic mouse line was created by phage artificial chromosome (PAC) transgenesis). This data enabled lineage trees for individual clones to be retrospectively drawn to include the timing of olig2 expression alongside the final identification of the daughter cells produced. In this way, the effects of different growth factors with respect to the induction of glial in preference to neuronal phenotypes were assessed. Using this system it was possible to determine what cell types could be derived from a single precursor and with what pattern within a lineage olig2 might be expressed under different culture conditions. Both FGF-2 and a Sonic Hedgehog agonist were seen to produce mixed clones in which olig2 was transcribed at early branch points within a lineage and later down-regulated in a selection of daughter cells. This means that olig2 expression does not denote commitment to the oligodendrocyte lineage and, furthermore, that induction is a sporadic event which seems to be dictated at the level of the individual progenitor cells rather than by an intrinsic cell-timer dictated within the original NEP.

APA, Harvard, Vancouver, ISO, and other styles

5

Stoney, Patrick Niall. "The roles of Pax6 in neural precursor migration and axon guidance." Thesis, University of Aberdeen, 2009. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=92509.

Full text

Abstract:

The ability of migrating neurons and growth cones to navigate through their environment is crucial for the correct development of the brain. Cells and growth cones may be guided by electrical, chemical or topographical cues in their environment. Pax6 is a transcription factor vital for brain development. Pax6-/- mutant mice die perinatally with defects in neuronal proliferation and differentiation, cortical cell migration and axon guidance, yet it is not clear which guidance cues Pax6-/- mutant neurons fail to interpret. Dissociated cultured cells were used to study the cell-autonomous effects of Pax6 mutation on guidance of growth cones and migrating neural precursors by environmental cues. Neurites from mouse embryonic cortical neurons aligned perpendicular to 1 μm-wide, 130 nm-deep substratum grooves. Pax6-/- mutation abolished contact-mediated neurite guidance by these grooves. Laminin induced a switch from perpendicular to parallel alignment to grooves, via a β1 integrin-independent mechanism. Blocking cAMP signalling abolished perpendicular alignment to polylysine-coated grooves, but enhanced parallel alignment to laminin-coated grooves. Pax6 null mutation or overexpression also caused specific defects in contact-guided migration by cortical cells. An electric field applied to E16.5 cortical neurons increased the frequency of extension of neurites aligned perpendicular to the field axis. Pax6-/- mutant cells responded to an electric field with reduced anodal extension, but no significant increase in perpendicular neurite extension. Electrical cues were prioritised over topographical cues when presented in combination. Taken together, data suggest that Pax6 mutant cortical cells do not completely lack the ability to detect extracellular guidance cues, but they respond differently to wild-type cells. In combination with other defects identified in the cortex, this may contribute to the cell migration and axon guidance phenotypes in the brain of the Pax6-/- embryo. This study also identified novel Pax6 expression in the trigeminal ganglion, where it may regulate axon guidance and neurogenesis.

APA, Harvard, Vancouver, ISO, and other styles

6

Jain, Meena. "Expanded neural precursor cells for the restorative therapy of Parkinson's disease." Thesis, University of Cambridge, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.431545.

Full text

APA, Harvard, Vancouver, ISO, and other styles

7

Lazic, Stanley Edward. "Endogenous neural precursor cells in transgenic mouse models of neurodegenerative disorders." Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.613659.

Full text

APA, Harvard, Vancouver, ISO, and other styles

8

Horiguchi, Satoshi. "Neural precursor cells derived from human embryonic brain retain regional specificity." Kyoto University, 2005. http://hdl.handle.net/2433/144744.

Full text

Abstract:

Kyoto University (京都大学)
0048
新制・課程博士
博士(医学)
甲第11420号
医博第2843号
新制||医||891(附属図書館)
23063
UT51-2005-D170
京都大学大学院医学研究科脳統御医科学系専攻
(主査)教授影山龍一郎, 教授大森治紀, 教授金子武嗣
学位規則第4条第1項該当

APA, Harvard, Vancouver, ISO, and other styles

9

Wylie, Crystal A. "P107 negatively regulates the neural precursor pool by repressing Hes1 transcription." Thesis, University of Ottawa (Canada), 2006. http://hdl.handle.net/10393/27198.

Full text

Abstract:

Stem cells are defined by their multipotentiality and their long-term ability to self-renew. P107, a member of the pocket protein family of cell cycle regulators has previously been shown in our laboratory to negatively regulate neural precursor cell number and self-renewal (Vanderluit et al., 2004). In this study, we investigated the mechanism by which p107 regulates the neural precursor pool by examining interactions between p107 and the Notch pathway, which has also been shown to regulate the neural stem cell population (Nakamura et al., 2000; Ohtsuka et al., 2001; Hitoshi et al., 2002b). We found an increase in both the transcript and protein levels of Hes1 in p107-/- brains using in situ hybridization and western blot analysis. Examination of the Hes1 promoter revealed three putative E2F binding sites, which were subsequently found to bind E2F3 and E2F4 using chromatin immunoprecipitation. P107 was found to significantly repress Hes1 promoter activity in the luciferase reporter assay, and finally, using the primary neurosphere assay we showed that removal of Hes1 from p107-/- neurospheres restores the number of neurosphere forming cells to wildtype levels. Our results suggest that p107 represses Hes1 transcription through E2F, and demonstrate that an upregulation of Hes1 is responsible for the increased neural precursor pool in p107-/- mice.

APA, Harvard, Vancouver, ISO, and other styles

10

Maciaczyk, Jaroslaw. "Human fetal neural precursor cells: a putative cell source for neurorestorative strategies." [S.l. : s.n.], 2005. http://nbn-resolving.de/urn:nbn:de:bsz:25-opus-57885.

Full text

APA, Harvard, Vancouver, ISO, and other styles

11

Geoffroy, Cédric. "Genetic manipulation to direct the differentiation of spinal cord neural precursor cells." Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612150.

Full text

APA, Harvard, Vancouver, ISO, and other styles

12

O'Keeffe, Gráinne Catherine. "The effect of dopamine on endogenous neural precursor cells in Parkinson's Disease." Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612288.

Full text

APA, Harvard, Vancouver, ISO, and other styles

13

Pakenham, Catherine. "Regulation of Neural Precursor Self-renewal via E2F3-dependent Transcriptional Control of EZH2." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/23812.

Full text

Abstract:

Our lab has recently found that E2F3, an essential cell cycle regulator, regulates the self-renewal capacity of neural precursor cells (NPCs) in the developing mouse brain. Chromatin immunoprecipitation (ChIP) and immunoblotting techniques revealed several E2F3 target genes, including the polycomb group (PcG) protein, EZH2. Further ChIP and immunoblotting techniques identified the neural stem cell self-renewal regulators p16INK4a and Sox2 as shared gene targets of E2F3 and PcG proteins, indicating that E2F3 and PcG proteins may co-regulate these target genes. E2f3-/- NPCs demonstrated dysregulated expression of EZH2, p16INK4a, and SOX2 and decreased enrichment of PcG proteins at target genes. Restoring EZH2 expression to E2f3+/+ levels restores p16INK4a and SOX2 expression levels to near E2f3+/+ levels, and also partially rescues NPC self-renewal capacity toward E2f3+/+ levels. Taken together, these results suggest that E2F3 controls NPC self-renewal by modulating expression of p16INK4a and SOX2 via regulation of PcG expression, and potentially PcG recruitment.

APA, Harvard, Vancouver, ISO, and other styles

14

Julian, Lisa. "Regulation of Neural Precursor Cell Fate by the E2f3a and E2f3b Transcription Factors." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/25489.

Full text

Abstract:

The classical cell cycle regulatory pathway is well appreciated as a key regulator of cell fate determination during neurogenesis; however, the extent of pRB/E2F function in neural stem and progenitor cells is not fully understood, and insight into the mechanisms underlying its connection with cell fate regulation are lacking. The E2F3 transcription factor has emerged as an important regulator of neural precursor cell (NPC) proliferation in the embryonic and adult forebrain, and we demonstrate here that it also influences the self-renewal potential of NPCs. Using knockout mouse models of individual E2F3 isoforms, we demonstrate the surprising result that the classical transcriptional activator E2F3a represses NPC self-renewal and promotes neuronal differentiation, while E2F3b promotes the expansion of the NPC pool and inhibits differentiation. We attribute these opposing activities to a unique mechanism of transcriptional regulation at the Sox2 locus, a key regulator of stem cell pluripotency, whereby E2F3a recruits transcriptional repressors to this site, and E2F3b promotes Sox2 activation. Importantly, E2F3a-mediated Sox2 regulation is necessary for cognitive function in the adult. Additionally, through the determination of genome-wide promoter binding sites for E2f3 isoforms as well as E2F4, another key regulator of NPC self-renewal, we determined that E2Fs are poised to regulate an extensive set of target genes with key roles in regulating diverse cell fate choices in NPCs, including self-renewal, cell death, progenitor expansion, maintenance of the precursor state, and differentiation. Together, these results reveal a diversity of function for E2Fs in the control of neural precursor cell fate, and identify E2F3 isoforms as important regulators of the pluripotency and stem cell maintenance gene Sox2.

APA, Harvard, Vancouver, ISO, and other styles

15

Eom, Tae-Yeon. "Regulation of neural precursor cell apoptosis and proliferation by glycogen synthase kinase-3." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2009. https://www.mhsl.uab.edu/dt/2009p/eom.pdf.

Full text

APA, Harvard, Vancouver, ISO, and other styles

16

Chen, Xia Milly. "Outcomes of neural precursor cell transplantation into the dentate gyrus of adult rat." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610314.

Full text

APA, Harvard, Vancouver, ISO, and other styles

17

Di, Lullo Elizabeth. "Pax6 and its paracrine activity in oligodendrocyte precursor cell migration in the developing neural tube." Paris 6, 2011. http://www.theses.fr/2011PA066737.

Full text

Abstract:

Cette thèse s'intéresse au rôle du transfert de l'homéoprotéine Pax6 dans la migration cellulaire, en utilisant le tube neural de poulet comme modèle. Nous avons utilisé la technique de biotinylation de surface pour démontrer la présence extracellulaire de Pax6. Cette observation a soulevé la question de l'importance physiologique in vivo de ce pool extracellulaire de Pax6 (ePax6). L'identification de cellules positives pour Pax6 à proximité de pr'curseurs d'oligodendrocytes (OPCs) en migration nous a conduit à formuler l'hypothèse d'un rôle de ePax6 dans la migration des OPCs. Cette hypothse a été testée in vitro et in vivo via des expériences de gain ou perte de fonction. Suite à la neutralisation de ePax6, nous avons observé une diminution du nombre d'OPCs en migration, suggérant ainsi que ePax6 est activement impliqué dans la dispersion des OPCs. A l'inverse, lorsque la protéine Pax6 est ajoutée dans le milieu de culture d'une préparation de type open book du tube neural, la dispersion des OPCs est accentuée. Un effet similaire est observé suite à l'électroporation in ovo d'un plasmide codant pour une forme de Pax6 dotée d'un signal peptide. Nos résultats suggèrent une action non-autonome de Pax6 nécessitant son internalisation par les OPCs. Ainsi, nos expériences de perte de fonction ont pour effet de réduire la quantité de protéine transférée dans les cellules cibles. L'ensemble de nos observations mettent en évidence que le rôle des homéoprotéines ne se réduit pas à une simple activité transcriptionnelle mais consiste plutôt en un large panel de processus incluant ce qui est peut tre leur fonction la plus ancienne : assurer la communication cellulaire

APA, Harvard, Vancouver, ISO, and other styles

18

Phillips, Wendy. "Endogenous neural precursor cells in the R6/2 transgenic mouse model of Huntington's disease." Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.614288.

Full text

APA, Harvard, Vancouver, ISO, and other styles

19

Liu, Min. "The effect of fluoxetine on neural precursor cell transplantation into the adult rat hippocampus." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608778.

Full text

APA, Harvard, Vancouver, ISO, and other styles

20

Furmanski, Orion. "Manipulating Embryonic Neural Precursor Cells for Therapeutic Transplantation into a Rat Model of Neuropathic Pain." Scholarly Repository, 2009. http://scholarlyrepository.miami.edu/oa_dissertations/340.

Full text

Abstract:

Persons with spinal cord injury (SCI) suffer life-long consequences including paralysis, loss of involuntary bodily functions, and chronic pain. A subset of SCI patients develop neuropathic pain (NP), a chronic condition resulting from damage to the spinal cord. Hyperexcitability of spinal cord sensory neurons near damaged tissue is believed to underlie SCI-related NP. Although many therapies have been employed clinically to combat SCI-NP, few give satisfactory long-term relief. Transplantation of cells that release GABA, a molecule that inhibits neuronal activity, is being explored as an alternative to current SCI-NP therapies. My experiments made progress toward preclinical modeling of GABA cell therapy for SCI-NP. First, I sought to determine whether quisqualic acid (QUIS)-induced SCI altered responses to tonic pain stimuli or altered GABAergic neural circuitry in rats. Second, I sought to determine whether a combination of genetic and trophic manipulations could promote a GABAergic phenotype in rat embryonic neural precursor cells (NPCs) in an in vitro culture system. The results revealed that QUIS-SCI rats exhibit unusually prolonged nocifensive responses to hind paw formalin injections. There was no significant difference between QUIS-SCI and sham surgery rats in c-Fos immunolabeling of spinal cord sensory neurons after formalin-induced neuronal activity. However, immunohistochemistry revealed substantial decreases in staining for markers of GABA presynaptic vesicles in injured spinal cord tissue. NPCs were enriched for a neuronal phenotype by combining withdrawal of the growth factor FGF-2 from culture media and overexpression of the transcription factor MASH1 in transfected cells. Although glial marker expression was suppressed in NPCs by these manipulations, expression of neuronal markers none the less declined through time. MASH1-overexpressing NPCs exhibited greater clonal expansion and decreased stress-induced PDI expression after FGF-2 withdrawal as compared to naïve. In light of existing data, these results suggest that the QUIS-SCI model may be useful for testing the efficacy of GABAergic NPC transplantation to reduce neuropathic pain. MASH1 overexpression and FGF-2 withdrawal could serve as a first step toward enriching GABA in NPCs for transplantation. Although the mechanism for MASH1 cytoprotection remains unclear, MASH1 may enhance survival of NPCs grafted into the spinal cord. These experiments contributed to the preclinical basis for application of therapeutic GABAergic stem cell transplantation for NP in human SCI patients.

APA, Harvard, Vancouver, ISO, and other styles

21

Luca, Luminita Eugenia. "Oxygen Glucose Deprivation and Hyperthermia Induce Cellular Damage in Neural Precursor Cells and Immature Neurons." Scholarly Repository, 2008. http://scholarlyrepository.miami.edu/oa_dissertations/184.

Full text

Abstract:

Hyperthermia damages both developing and adult brains, especially when it occurs after ischemia or stroke. Work presented in this dissertation used in vitro models of these stresses to investigate mechanisms underlying damage to immature neurons and neural precursors cultured from embryonic rat brain. Studies described in Chapter 2 investigated the effects of a brief, intense hyperthermic stress (30-45 min at 43ºC). This stress produced a selective depletion of nestin-immunoreactive neural precursor cells, and reduced proliferation, as evidenced by reduced BrdU incorporation into young Tuj1-immunoreactive neurons. The stress activated caspase 3, and produced multiple signs of nuclear damage as well as early and persisting mitochondrial depolarization. Cycloheximide, an inhibitor of protein synthesis, reduced cell death. All these findings suggest an apoptotic death process. Studies described in Chapter 3 used a combination of oxygen-glucose deprivation (OGD, 2 h) followed by mild 41ºC hyperthermia for 90 min (T). The combined OGDT stress reduced both survival in monolayer cultures and colony-forming ability in neurospheres. Cell death occurred gradually over 2 days, and was accompanied by caspase activation that began within 6 h post-stress. Post-stress application of cycloheximide or a general caspase inhibitor (especially qVD-OPH) reduced cell death, but specific inhibitors of caspases 2, 3, 8 or 9 were ineffective. OGDT led to upregulation of the pro-apoptotic protein Bim as well as redistribution of Bax from cytoplasm to mitochondria within 6 h. Persisting mitochondrial depolarization began within 3 h following the combined OGDT stress, but not following individual OGD or T stresses alone. These findings suggest that OGD sensitizes neural precursor cells to hyperthermia-induced damage, and that the combined OGDT stress kills neural precursors via apoptotic mechanisms that include activation of mitochondrial death pathways. Results of these studies suggest that immature neurons and neural precursors are especially vulnerable to hyperthermia-induced damage via apoptotic mechanisms. Pan-caspase inhibitors may be a promising therapeutic strategy to preserve viability of these cells following stroke with hyperthermia.

APA, Harvard, Vancouver, ISO, and other styles

22

Babu, Harish [Verfasser]. "Isolation and characterization of neural precursor cells in the adult murine dentate gyrus / Harish Babu." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2008. http://d-nb.info/1022854968/34.

Full text

APA, Harvard, Vancouver, ISO, and other styles

23

Darcy, Daniel Paul. "Physiological properties and factors affecting migration of neural precursor cells in the adult olfactory bulb." Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2007. http://wwwlib.umi.com/cr/ucsd/fullcit?p3284209.

Full text

Abstract:

Thesis (Ph. D.)--University of California, San Diego, 2007.
Title from first page of PDF file (viewed January 11, 2008). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 71-76).

APA, Harvard, Vancouver, ISO, and other styles

24

Ostenfeld, Thor. "Neural precursor cells : strategies for cell-mediated neuroprotection and regeneration in the nigro-striatal system." Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620592.

Full text

APA, Harvard, Vancouver, ISO, and other styles

25

Haupt, Borris. "Herpes simplex virus-1 (HSV-1) as a gene delivery vector for neural precursor cells." Thesis, University College London (University of London), 2004. http://discovery.ucl.ac.uk/1446639/.

Full text

Abstract:

The thesis work presented evaluated the potential for use of disabled herpes simplex virus-1 (HSV-1) as gene delivery vectors for neural precursor cells and studied the effects of delivered recombinant factors on the de novo development of dopaminergic neurons from neural precursor cells. Highly and less disabled HSV-1 has been studied with respect to gene delivery efficiency and effects on cellular integrity in primary neural progenitor cells, neural stem cells grown as neurospheres, and in endogenous neural stem cell niches in the adult rat. Data from autografts of virally transduced neurospheres into the striatum of rats were also presented. The characteristics of virally transduced neural precursor cells were compared to other viral vector systems reported in literature. With respect to the study of differentiation factors, work has concentrated on fibroblast growth factor 8b (FGF8b). This has demonstrated that FGF8b is a mitogen for neural precursor cells in vitro. The study showed that neural stem cells isolated from different regions of the developing brain can be expanded in FGF8b alone and retain their stem cell characteristics, e.g. the capacity of self-renewal and multipotentiality. Growth curves and dose responses of neural precursor cells expanded in FGF8b further confirmed these findings. The study also showed survival effects of FGF8b on dopaminergic neurons derived from mesencephalic precursor cells. Further the effects of FGF8b on proliferation and differentiation of endogenous stem cells were also investigated. Finally, the thesis work involved the construction and generation of highly and less disabled viruses expressing FGF8b, sonic hedgehog, basic fibroblast growth factor, and the transcription factor nurr1. Expression and bioactivity of the various constructs was confirmed. The effects of these factors on dopamine neuron development were then studied in vitro using neural progenitors and neural precursor cells for which gene delivery had been optimized in the first part of this thesis.

APA, Harvard, Vancouver, ISO, and other styles

26

Gomi, Masanori. "Single and local blockade of IL-6 signaling promotes neuronal differentiation from transplanted embryonic stem cell-derived neural precursor cells." Kyoto University, 2011. http://hdl.handle.net/2433/147334.

Full text

APA, Harvard, Vancouver, ISO, and other styles

27

Bernas, Stefanie [Verfasser], Gerd [Gutachter] Kempermann, and Ludwig [Gutachter] Aigner. "Neural Precursor Cells in Culture: Taking a Closer Look / Stefanie Bernas ; Gutachter: Gerd Kempermann, Ludwig Aigner." Dresden : Technische Universität Dresden, 2019. http://d-nb.info/1227196555/34.

Full text

APA, Harvard, Vancouver, ISO, and other styles

28

Bernas, Stefanie Verfasser], Gerd [Gutachter] [Kempermann, and Ludwig [Gutachter] Aigner. "Neural Precursor Cells in Culture: Taking a Closer Look / Stefanie Bernas ; Gutachter: Gerd Kempermann, Ludwig Aigner." Dresden : Technische Universität Dresden, 2019. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa2-327454.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

Chintawar, Satyan. "Neural precursor cells: interaction with blood-brain barrier and neuroprotective effect in an animal model of cerebellar degeneration." Doctoral thesis, Universite Libre de Bruxelles, 2009. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210202.

Full text

Abstract:

Adult neural precursor cells (NPCs) are a heterogeneous population of mitotically active, self-renewing multipotent cells of both adult and developing CNS. They can be expanded in vitro in the presence of mitogens. The B05 transgenic SCA1 mice, expressing human ataxin-1 with an expanded polyglutamine tract in cerebellar Purkinje cells (PCs), recapitulate many pathological and behavioral characteristics of the neurodegenerative disease spinocerebellar ataxia type 1 (SCA1), including progressive ataxia and PC loss. We transplanted neural precursor cells (NPCs) derived from the subventricular zone of GFP-expressing adult mice into the cerebellar white matter of SCA1 mice when they showed absent (5 weeks), initial (13 weeks) and significant PC loss (24 weeks). A stereological count demonstrates that mice with significant cell loss exhibit highest survival of grafted NPCs and migration to the vicinity of PCs as compared to wt and younger grafted animals. These animals showed improved motor skills as compared to sham animals. Confocal analysis and profiling shows that many of implanted cells present in the cerebellar cortex have formed gap junctions with host PCs and express connexin43. Grafted cells did not adopt characteristics of PCs, but stereological and morphometric analysis of the cerebellar cortex revealed that grafted animals had more surviving PCs and a better preserved morphology of these cells than the control groups. Perforated patch clamp recordings revealed a normalization of the PC basal membrane potential, which was abnormally depolarized in sham-treated animals. No significant increase in levels of several neurotrophic factors was observed, suggesting, along with morphological observation, that the neuroprotective effect of grafted NPCs was mediated by direct contact with the host PCs. In this study, evidence for a neuroprotective effect came, in addition to motor behavior improvement, from stereological and electrophysiological analyses and suggest that timing of stem cell delivery is important to determine its therapeutic effect.

In a brain stem cell niche, NSCs reside in a complex cellular and extracellular microenvironment comprising their own progeny, ependymal cells, numerous blood vessels and various extracellular matrix molecules. Recently, it was reported that blood vessel ECs-NSCs crosstalk plays an important role in tissue homeostasis. Bloodstream offers a natural delivery vehicle especially in case of diffuse neurodegenerative diseases which require widespread distribution of exogenous cells. As NSCs are confronted with blood-brain barrier endothelial cells (BBB-ECs) before they can enter into brain parenchyma, we investigated their interaction using primary cultures in an in vitro BBB model. We isolated human fetal neural precursor cells (hfNPCs) from aborted fetal brain tissues and expanded in vitro. We showed that in an in vitro model, human BBB endothelium induces the rapid differentiation of hfNPCs and allows them to cross the endothelial monolayer, with the differentiated progeny remaining in close contact with endothelial cells. These results are not reproduced when using a non-BBB endothelium and are partly dependent on the cytokine MCP1. Our data suggest that, in the presence of attractive signals released by a damaged brain, intravascularly administered NPCs can move across an intact BBB endothelium and differentiate in its vicinity. Overall, our findings have implications for the development of cellular therapies for cerebellar degenerative diseases and understanding of the brain stem cell niche.
Doctorat en Sciences biomédicales et pharmaceutiques
info:eu-repo/semantics/nonPublished

APA, Harvard, Vancouver, ISO, and other styles

30

Challapa, Velásquez Nancy Mariela. "Fisicoquímica del neurotransmisor dopamina y su precursor L-DOPA utilizando métodos teóricos y experimentales." Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2018. https://hdl.handle.net/20.500.12672/8026.

Full text

Abstract:

Publicación a texto completo no autorizada por el autor
Estudia las propiedades de estabilidad termodinámica y reactividad por transferencia protónica intrínsecas (en fase gas) del neurotransmisor dopamina y su precursor L-DOPA. Para ello hace uso de la Metodología DFT (B3LYP) y “ab-initio” (métodos G3 y G4) para el estudio conformacional en especies neutras, protonadas y desprotonadas, en fase gaseosa; y la determinación experimental, mediante espectrometría de masas de triple-cuadrupolo con fuente ESI (electrospray), de la afinidad protónica y basicidad de la Dopamina y acidez de la L-DOPA en fase gaseosa, aplicando el Método Cinético Extendido de Cooks (EKCM).
Tesis

APA, Harvard, Vancouver, ISO, and other styles

31

Hirotsu, Akiko. "Maternal exposure to volatile anesthetics induces IL-6 in fetal brains and affects neuronal development." Kyoto University, 2020. http://hdl.handle.net/2433/253146.

Full text

APA, Harvard, Vancouver, ISO, and other styles

32

Deshpande, Sachin S. [Verfasser], and Christian [Akademischer Betreuer] Schachtrup. "The role of the p75 neurotrophin receptor (p75NTR) in adult neural stem/precursor cell properties after cortical injury." Freiburg : Universität, 2020. http://d-nb.info/1212361121/34.

Full text

APA, Harvard, Vancouver, ISO, and other styles

33

Mitrugno, Valentina Maria <1983&gt. "Sonic Hedgehog pathway impairment in Neural Precursor Cells of the Ts65Dn mouse, an animal model of Down syndrome." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4601/.

Full text

Abstract:

Mental retardation in Down syndrome (DS) has been imputed to the decreased brain volume, which is evident starting from the early phases of development. Recent studies in a widely used mouse model of DS, the Ts65Dn mouse, have shown that neurogenesis is severely impaired during the early phases of brain development, suggesting that this defect may be a major determinant of brain hypotrophy and mental retardation in individuals with DS. Recently, it has been found that in the cerebellum of Ts65Dn mice there is a defective responsiveness to Sonic Hedgehog (Shh), a potent mitogen that controls cell division during brain development, suggesting that failure of Shh signaling may underlie the reduced proliferation potency in DS. Based on these premises, we sought to identify the molecular mechanisms underlying derangement of the Shh pathway in neural precursor cells (NPCs) from Ts65Dn mice. We found that the expression levels of the Shh receptor Patched1 (Ptch1) were increased compared to controls both at the RNA and protein level. Partial silencing of Ptch1 expression in trisomic NPCs restored cell proliferation, indicating that proliferation impairment was due to Ptch1 overexpression. We further found that the overexpression of Ptch1 in trisomic NPCs is related to increased levels of AICD, a transcription-promoting fragment of amyloid precursor protein (APP). Increased AICD binding to the Ptch1 promoter favored its acetylated status, thus enhancing Ptch1 expression. Taken together, these data provide novel evidence that Ptch1 over expression underlies derangement of the Shh pathway in trisomic NPCs, with consequent proliferation impairment. The demonstration that Ptch1 over expression in trisomic NPCs is due to an APP fragment provides a link between this trisomic gene and the defective neuronal production that characterizes the DS brain.

APA, Harvard, Vancouver, ISO, and other styles

34

Li-Kroeger, David. "Integration of regional and neural transcription factors controls EGF signaling from sensory organ precursor cells during Drosophila development." University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1337351052.

Full text

APA, Harvard, Vancouver, ISO, and other styles

35

Le, Grand Jaclyn Nicole. "Mcl-1 is a key regulator of apoptosis in neural precursor cells and autophagy in post-mitotic neurons." Thesis, University of Ottawa (Canada), 2009. http://hdl.handle.net/10393/28096.

Full text

Abstract:

Unregulated neuronal cell death has been implicated in the pathogenesis of several neurological disorders and in acute neuronal injury such as stroke. Mcl-1, an anti-apoptotic member of the Bcl-2 family, is a known survival factor for hematopoietic cells, however little is known regarding its function in the nervous system. In this study, we examined the role of Mcl-1 in regulation of programmed cell death throughout nervous system development and in maintaining mature neurons. We found that both Nestin: Cre Mcl-1 and Foxg1: Cre Mcl-1 conditional knockout mice were embryonic lethal. Morphological analysis and immunohistochemical staining revealed severe deterioration of the cortices and an apoptotic phenotype, suggesting that Mcl-1 is required for embryonic neuronal survival. Both neural progenitors and newly differentiated neurons were affected, revealing that neurons were dying throughout the process of differentiation. Deletion of Mcl-1 in post mitotic neurons in postnatal mice with CamKIIalpha Cre also resulted in premature lethality. Cresyl Violet staining and NeuN immunohistochemistry revealed a rapid loss of neurons in the cortices of mutants. Electron micrographic imaging revealed double membraned vesicles within the cortical neurons, suggestive of an autophagic form of cell death. Consistent with this hypothesis, an upregulation of LC3 was observed in primary cortical neurons deficient for Mcl-1. Altogether our findings demonstrate that the loss of Mcl-1 in embryonic and post-mitotic neurons results in cell death. The two distinct forms of cell death activated indicate that Mcl-1 functions in multiple pathways to promote neuronal survival. In summary, we demonstrate that Mcl-1 is vital for the survival of neurons.

APA, Harvard, Vancouver, ISO, and other styles

36

Schober, Maria. "Isolierung und Charakterisierung von Sphäroide bildenden Vorläuferzellen aus der ovinen Dermis." Doctoral thesis, Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-144880.

Full text

Abstract:

Die Inzidenz von neurodegenerativen Erkrankungen und Schlaganfällen steigt in Folge der Überalterung der westlichen Gesellschaft immer weiter an. Die Behand-lung von Schlaganfall-, Alzheimer und Parkinsonpatienten ist bisher aber meist unbefriedigend bzw. weitgehend erfolglos. Ein neues Modell in der Schlaganfallforschung wurde daher am Schaf entwickelt. In diesem wird auch der in den letzten zwei Jahrzehnten verstärkt verfolgte zelltherapeutische Ansatz untersucht (BOLTZE et al. 2011, DREYER et al. 2012). Neurale Vorläuferzellen gelten dabei, auf Grund ihrer wichtigen Rolle bei den endogenen Reparaturmechanismen nach einem Schlaganfall, als besonders vielversprechend. Die Gewinnung dieser Zellen für eine autologe Transplantation ist jedoch aufwendig und nur eingeschränkt möglich. Im Vergleich zu Nervengewebe stellt die Haut eine sowohl beim Tier als auch beim Menschen leicht zugängliche und in ausreichendem Maß verfügbare Quelle verschiedener Stamm- und Vorläuferzellen dar. Bei verschiedenen Spezies wurde die Isolation spezieller, dermaler Vorläuferzellen beschrieben, die als skin-derived precursor cells (SKPs) bezeichnet werden. SKPs wiesen dabei ein ähnliches Differenzierungspotential auf wie neurale Vorläuferzellen (TOMA et al. 2001, FERNANDES et al. 2006). Ein Einsatz der SKPs in der Schlaganfalltherapie wäre somit denkbar, muss aber zunächst im Schafmodell erforscht werden. SKPs wurden jedoch noch nicht bei der Spezies Schaf isoliert. Ziel der vorliegenden Arbeit war es daher, ein Isolationsprotokoll für SKPs aus der ovinen Dermis zu etablieren und diese morphologisch und immunzytologisch zu charakterisieren. Im Rahmen dieser Arbeit wurden verschiedene in der Literatur beschriebene Isolati-onsverfahren an ovinen Hautproben getestet und modifiziert. Es wurden verschiedene Körperregionen auf ihre Eignung zur Probenentnahme und zur anschließenden Isolierung untersucht. Des Weiteren wurde der Effekt einer Rasur eine Woche vor Exzision des Hautareals auf die Sphäroidbildung überprüft. Der Einsatz von Enzymen in Kombinationslösungen oder singulär wurde variiert und eine unterschiedlich intensive mechanische Aufbereitung der Proben durchgeführt. Der Erfolg der zwei vielversprechendsten Isolationsprotokolle wurde statistisch validiert. Außerdem wurde der Effekt einer initialen Fibronektinbeschichtung analysiert. Die von den isolierten Zellen gebildeten sphärenartigen Zellaggregate wurden unter morphologischen Gesichtspunkten sechs und neun Wochen nach Isolation ausgewertet. Dabei wurden die Anzahl der Sphäroide/cm², die Größe und die Form berücksichtigt. Des Weiteren erfolgte eine immunzytologische Analyse der Sphäroide mit Fokus auf das in der Literatur beschriebene Expressionsmuster von SKPs und neuralen Vorläuferzellen. Für die Isolation von ovinen SKPs erwies sich die Regio nasofrontalis als das geeignetste Hautareal. Dabei war die Isolation eine Woche nach Rasur des beprobten Areals zuverlässiger als ohne diese. Bei vergleichender Betrachtung der Methoden erwies sich ein enzymatisch orientiertes Isolationsverfahren modifiziert nach FERNANDES und MILLER (2009) als zielführend. Neben einer hohen Anzahl an isolierten Zellen erfolgte in jedem Versuchsdurchgang eine Zusammenlagerung der Zellen in frei flotierenden Aggregaten. Diese waren im Median 70,97 µm groß. Auf Grund ihrer Geometrie ist es korrekter sie als Sphäroide und nicht, wie bei anderen Spezies üblich, als Sphären zu bezeichnen. Eine anfängliche Beschichtung der Zellkulturplatten mit Fibronektin hatte keinen fördernden Effekt auf die Bildung und die Größe der Sphäroide. Lediglich eine anfänglich höhere Proliferationsrate war bemerkbar. Immunzytologisch konnte gezeigt werden, dass in den Sphäroiden eine heterogene Zellpopulation vorlag. Die Sphäroide wurden überwiegend von Zellen gebildet, in denen neben mesenchymalen Markern auch klassische Vorläuferantigene wie Nestin und Sox2 nachgewiesen wurden. Das immunzytologische Expressionsmuster ist damit vergleichbar mit dem von SKPs anderer Spezies. Außerdem wurden in unterschiedlicher Ausprägung Antigene detektiert, die typischerweise in neuralen Vorläuferzellen der ventrikulären und subventrikulären Zone vorkommen. Dies konnte auch in den Positivkontrollen für das ovine Gehirn bestätigt werden. Die Anzahl proliferierender Zellen in den Sphäroiden war relativ gering und die Anzahl an kokultivierter Keratinozyten minimal. Die Zusammenfassung der heterogenen Vorläuferzellpopulation unter dem Begriff skin-derived precursor cells ist auf Grund ihres dermalen Ursprungs und ihrer morphologischen und immunzytologischen Eigenschaften gerechtfertigt. Somit ist es in dieser Arbeit gelungen, zum ersten Mal SKPs aus der ovinen Dermis zu isolieren und über neun Wochen zu kultivieren. Es wurde ein Isolationsprotokoll entwickelt, das eine Sphäroidbildung reproduzierbar ermöglicht und an die Gegebenheiten beim Schaf angepasst ist. Bevor eine autologe Transplantation von diesen SKPs etwa im Schlaganfallmodell am Schaf vorgenommen werden kann, ist eine intensivere Untersuchung der isolierten Zellen etwa mittels PCR durchzuführen und eine fluoreszenzbasierte Zellsortierung der heterogenen Vorläuferzellen zu entwickeln
In consequence of the demographic changes in modern western society, the inci-dence of neurodegenerative diseases and stroke is increasing. Unfortunately, there is still no successful or at least satisfactory treatment available for patients who suffer from stroke Alzheimer’s or Parkinson’s disease. Therefore, a new animal model in stroke research has been established in sheep (BOLTZE et al. 2011, DREYER et al. 2012). First cell therapy studies have already been performed in this model. Especially neural precursor cells seem to be promising as they play an important role in endogenous repair processes in the brain after stroke. However, the extraction of these cells prior to an autologous transplantation is elaborate and of limited success. Compared to neural tissue, skin is an easily accessible and sufficiently available source of a variety of stem and precursor cells in animals as well as in humans. Thus, the isolation of a specific type of dermal precursor cells, called skin-derived precursor cells (SKPs), seems to be easier compared to neural precursor cells and in vitro SKPs are capable of neural differentiation as well (TOMA et al. 2001, FERNANDES et al. 2006). According to these findings, a therapeutic application of SKPs after stroke seems to be promising. Prior to that, however, intensive studies in the ovine stroke model are necessary. Thus, SKPs have to be isolated from the dermis of sheep for an autologous transplantation. Therefore, the aim of this dissertation has been the establishment of an optimal isolation protocol for SKPs from the ovine dermis as well as the morphological and by immunocytochemical characterisation of those cells. Within this study, several previously described isolation protocols were modified for ovine skin. Skin samples were taken from several body regions to assess the local suitability for excision and isolation. Additionally, the effect of shaving the areas one week before sampling on spheroid forming was tested. A variety of enzymes was used alone and in combination. Furthermore, the effectiveness of an isolation protocol using enhanced mechanical treatment was analysed. The two most promising protocols were evaluated statistically and compared to each other. In these experiments, the influence of an initial fibronectin coating was determined as well. The isolated cells formed spheroids, which were assessed after six and nine weeks of cultivation considering the amount of spheroids per cm², their size and form. Moreover, immunocytochemical tests were conducted, focusing on expression patterns described for SKPs and neural precursor cells. According to these experiments, it is advisable to take skin samples from the naso-frontal region one week after shaving. Comparing all tested protocols, a predominantly enzymatic isolation protocol modified according to FERNANDES and MILLER (2009) was most successful. A high cell yield was achieved and free-floating spheroids formed spontaneously in all test runs. The median diameter of these spheroids was 70.97 µm. Due to their three-dimensional shape, it is more correct to use the term “spheroid” instead of the commonly used term “sphere”. Growing the isolated cells initially on fibronectin coated culture plates does not support both formation and size of the spheroids. Only a higher cell proliferation at the beginning of cultivation can be noticed. Immunocytochemical assays demonstrated that the formed spheroids consisted of a heterologous cell population. Besides mesenchymal antigens the cells in the spheroids expressed characteristic antigens of precursor cells, like Nestin and Sox2. Thus, the immunocytochemical expression pattern is comparable to SKPs isolated from other species. Furthermore, common markers of neural precursor cells of the ventricular and subventricular zone, whose existence in the ovine brain was also proven in this study, were detected in the spheroid forming cells. There were only a few proliferating cells and a minimal amount of keratinocytes in the spheroids. Due to the dermal origin and the given morphological and immunocytochemical characteristics, the heterogeneous cell population can be addressed by the term “skin-derived precursor cells”. In conclusion, in this study ovine SKPs were isolated for the first time and cultured successfully over nine weeks. An isolation protocol was established, which guarantees reproducible formation of spheroids in cell isolates from ovine dermis. Further intensive examinations of the isolated cells, for example using PCR, have to be conducted before SKPs can be applied in autologous transplantation in the ovine stroke model. Additionally, the usage of fluorescence-activated cell sorting of the heterogeneous precursor cells should be considered

APA, Harvard, Vancouver, ISO, and other styles

37

Yang, Xiaoying. "Effect of nitric oxide on the proliferation and differentiation of neural precursor cells derived from embryonic rat spinal cord." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B44229331.

Full text

APA, Harvard, Vancouver, ISO, and other styles

38

Deshpande, Nirupama. "Investigations on formation and specification of neural precursor cells in the central nervous system of the Drosophila melanogaster embryo." [S.l. : s.n.], 2001. http://ArchiMeD.uni-mainz.de/pub/2001/0133/diss.pdf.

Full text

APA, Harvard, Vancouver, ISO, and other styles

39

Yang, Xiaoying, and 杨晓英. "Effect of nitric oxide on the proliferation and differentiation of neural precursor cells derived from embryonic rat spinal cord." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B44229331.

Full text

APA, Harvard, Vancouver, ISO, and other styles

40

Armstrong, Richard James Ernest. "Cell replacement therapy through transplantation of expanded neural precursor cells : experiments in animal models of Parkinson's and Huntington's diseases." Thesis, University of Cambridge, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.431572.

Full text

APA, Harvard, Vancouver, ISO, and other styles

41

Carter, Calvin Stanley. "Characterizing the role of primary cilia in neural progenitor cell development and neonatal hydrocephalus." Diss., University of Iowa, 2014. https://ir.uiowa.edu/etd/4587.

Full text

Abstract:

Neonatal hydrocephalus is a common neurological disorder leading to expansion of the cerebral ventricles. This disease is associated with significant morbidity and mortality and is often fatal if left untreated. Hydrocephalus was first described over 2500 years ago by Hippocrates, the father of medicine, and remains poorly understood today. Current therapies still rely on invasive procedures developed over 60 years ago that are associated with high failure and complication rates. Thus, the identification of molecular mechanisms and the development of non-invasive medical treatments for neonatal hydrocephalus are high priorities for the medical and scientific communities. The prevailing doctrine in the field is that hydrocephalus is strictly a "plumbing problem" caused by impaired cerebrospinal fluid (CSF) flow. Recently, animal models with impaired cilia have provided insight into the mechanisms involved in communicating (non-obstructive) hydrocephalus. However, as a result of a poor understanding of hydrocephalus, no animal studies to date have identified an effective non-invasive treatment. The goal of this thesis project is to investigate the molecular mechanisms underlying this disease and to identify a non-invasive, highly effective treatment strategy. In Chapter 2, we utilize a novel animal model with idiopathic hydrocephalus, mimicking the human ciliopathy Bardet-Biedl Syndrome (BBS), to examine the role of cilia in hydrocephalus. We find that these mice develop communicating hydrocephalus prior to the development of ependymal "motile" cilia, suggesting that this phenotype develops as a result of dysfunctional "primary" cilia. Primary cilia are non-motile and play a role in cellular signaling. These results challenge the current dogma that dysfunctional motile cilia underlies neonatal hydrocephalus and implicate a novel role for primary cilia and cellular signaling in this disease. Chapter 3 focuses on identifying the link between primary cilia and neonatal hydrocephalus. In this chapter, we report that disrupting the molecular machinery within primary cilia leads to faulty PDGFRα signaling and the loss of a particular class of neural progenitor cells called oligodendrocyte precursor cells (OPCs). We find that the loss of OPCs leads to neonatal hydrocephalus. Importantly, we identify the molecular mechanism underlying both the loss of OPCs and the pathogenesis of neonatal hydrocephalus. Chapter 4 explores the therapeutic potential of targeting the defective cellular signaling pathways to treat neonatal hydrocephalus. By targeting the faulty signaling, we restore normal development of oligodendrocyte precursor cells, and curtail the development of hydrocephalus. This work challenges the predominant view of hydrocephalus being strictly a "plumbing problem" treatable solely by surgical diversion of CSF. Here, we propose that hydrocephalus is a neurodevelopmental disorder that can be ameliorated by non-invasive means. Importantly, we introduce novel molecular targets and a non-invasive treatment strategy for this devastating disorder. To our knowledge, we are the first to successfully treat neonatal hydrocephalus in any model organism by targeting neural progenitor cells.

APA, Harvard, Vancouver, ISO, and other styles

42

Sakamoto, Masami. "The Basic Helix-Loop-Helix Genes Hesr1/Hey1 and Hesr2/Hey2 Regulate Maintenance of Neural Precursor Cells in the Brain." Kyoto University, 2004. http://hdl.handle.net/2433/147494.

Full text

APA, Harvard, Vancouver, ISO, and other styles

43

Padam, Amith Chordia. "Development and Commercialization of Remyelination Therapeutics to Restore Neural Function in Multiple Sclerosis." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1304690351.

Full text

APA, Harvard, Vancouver, ISO, and other styles

44

Daus, Janice Mabutas. "Assessing Epidermal Growth Factor Expression in the Rodent Hippocampus Following Traumatic Brain Injury." VCU Scholars Compass, 2006. http://hdl.handle.net/10156/1463.

Full text

APA, Harvard, Vancouver, ISO, and other styles

45

Vrotsos, Emmanuel George. "MCP-1 and APP involvement in glial differentiation and migration of neuroprogenitor cells." Orlando, Fla. : University of Central Florida, 2009. http://purl.fcla.edu/fcla/etd/CFE0002517.

Full text

APA, Harvard, Vancouver, ISO, and other styles

46

Gu, Song [Verfasser], and Rainer [Akademischer Betreuer] Glaß. "Decreased demand for olfactory periglomerular cells impacts on neural precursor cell viability in the rostral migratory stream / Song Gu ; Betreuer: Rainer Glaß." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2018. http://d-nb.info/1175381659/34.

Full text

APA, Harvard, Vancouver, ISO, and other styles

47

Lodato, Michael A. (Michael Anthony). "Sox2 co-occupies distal enhancer elements with cell-type-specific POU factors to specify cell identity in embryonic stem cells and neural precursor cells." Thesis, Massachusetts Institute of Technology, 2012. http://hdl.handle.net/1721.1/72631.

Full text

Abstract:

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, June 2012.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
"June 2012." Cataloged from student submitted PDF version of thesis.
Includes bibliographical references.
Sox2 is a master regulator of two distinct cellular states, that of pluripotent embryonic stem cells (ESCs) and multipotent neural progenitor cells (NPCs), but what common or distinct roles Sox2 may play in these cell types not fully understood. Further, the molecular mechanisms by which Sox2 can specify two distinct cell identities are as of yet unclear. This thesis is aimed at answering these fundamental questions. In ESCs, Sox2 was associated with a subset of poised regulators of nervous system development, and upon differentiation into NPCs Sox2 selectively activates those which are important for progenitor cell state, while keeping others poised to become activated in later neural development. These data suggested that Sox2 might act as a pioneer factor for neural development throughout embryogenesis. While Sox2 is known to co-occupy target loci in ESCs with the POU factor Oct4, in NPCs Sox2 interacts with the central-nervous-system-expressed POU factors Brn1 and Brn2. By utilizing distinct composite Sox:Octamer motifs in each cell type, Sox2:POU modules control the expression of thousands of genes involved in the development of the neural lineage in a cell-type-specific manner. These data advance our understanding of the mechanism by which transcription factors control cell fate transitions, and indicate that combinatorial interactions between transcription factors may be a pervasive mechanism of transcriptional control in development
by Michael A. Lodato.
Ph.D.

APA, Harvard, Vancouver, ISO, and other styles

48

Makedonopoulou, Paraskevi. "Studying the molecular consequences of the t(1;11) balanced translocation using iPSCs derived from carriers and within family controls." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/25871.

Full text

Abstract:

Schizophrenia is a major psychiatric disorder that affects 1% of the world population and is among the 10 leading worldwide causes of disability. Disrupted-In- Schizophrenia (DISC1) is one of the most studied risk genes for mental illness and is disrupted by a balanced translocation between chromosomes 1 and 11 that co-segregates with major mental illness in a single large Scottish family. DISC1 is a scaffold protein with numerous interactors and has been shown to hold key roles in neuronal progenitor proliferation, migration, cells signalling and synapse formation and maintenance. The studies herein provide the platform in order to investigate the molecular and cellular consequences of the t(1;11) translocation using induced pluripotent stem cells (iPSCs)-derived neural precursor cells and neurons from within-family carriers and controls. Towards this end, several iPSC lines have been converted into neural progenitor cells (NPCs) and differentiated into physiologically active forebrain neurons following well-characterised protocols. These cells were characterised in terms of basic marker expression at each developmental stage. Inter-line variation was observed in all subsequent experiments but overall t(1;11) lines did not generate less neuronal or less proliferating cells compared to control lines. Furthermore, the expression pattern of genes disrupted by the t(1;11) translocation was investigated by RT-qPCR. DISC1 was reduced by ~50% in the translocation lines, both neural precursors and neurons. This observation corresponds to previous findings in lymphoblastoid cell lines (LBCs) derived from members of the same family. Moreover, DISC1 expression was found to increase as neural precursors differentiation to neurons. Two other genes are disrupted by the t(1;11) translocation;DISC2 and DISC1FP1. Their expression was detectable, but below the threshold of quantification. Similarly, DISC1/DISC1FP1 chimeric transcripts corresponding to such transcripts previously identifies in LBCs from the family were detectable, but not quantifiable. A fourth gene, TSNAX, was also investigated because it is located in close proximity to, and undergoes intergenic splicing with, DISC1. Interestingly, TSNAX was found to be altered in some but not all time points studied, in the translocation carriers compared to control lines. In addition to breakpoint gene expression profiling, iPSC-derived material was used to investigate neuronal differentiation. There seemed to be attenuation in BIII-TUBULIN expression at two weeks post-differentiation, while NESTIN, MAP2 and GFAP expression was similar between translocation carrier and control lines at all time points studied. I also had access to targeted mice designed to mimic the derived chromosome 1 of the t(1;11) balanced translocation. Using RT-qPCR Disc1 expression was found to be 50% lower in heterozygous mice compared to wild types, and I detected a similar profile of chimeric transcript expression as detected in translocation carrier-derived LBCs. These observations support my gene expression studies of the human cells and indicate that the iPSC-derived neural precursors and neurons can be studied in parallel with the genome edited mice to obtain meaningful insights into the mechanism by which the t(1;11) translocation confers substantially elevated risk of major mental illness. In conclusion, the studies described in this thesis provide an experimental platform for investigation of the effects of the t(1;11) translocation upon function and gene and protein expression in material derived from translocation carriers and in brain tissue from a corresponding mouse model.

APA, Harvard, Vancouver, ISO, and other styles

49

Adusumilli, Vijaya [Verfasser], Gerd [Gutachter] Kempermann, and Mike O. [Gutachter] Karl. "Investigating the role of cell-autonomous ROS status in the regulation of hippocampal neural precursor cells in adult mice / Vijaya Adusumilli ; Gutachter: Gerd Kempermann, Mike O. Karl." Dresden : Technische Universität Dresden, 2020. http://d-nb.info/1227311923/34.

Full text

APA, Harvard, Vancouver, ISO, and other styles

50

Adusumilli, Vijaya Verfasser], Gerd [Gutachter] [Kempermann, and Mike O. [Gutachter] Karl. "Investigating the role of cell-autonomous ROS status in the regulation of hippocampal neural precursor cells in adult mice / Vijaya Adusumilli ; Gutachter: Gerd Kempermann, Mike O. Karl." Dresden : Technische Universität Dresden, 2020. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa2-728027.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Dissertations / Theses on the topic 'Neural precursor'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles