scholarly journals Regulation of neural progenitor cell state by ephrin-B

2008 ◽  
Vol 181 (6) ◽  
pp. 973-983 ◽  
Author(s):  
Runxiang Qiu ◽  
Xiuyun Wang ◽  
Alice Davy ◽  
Chen Wu ◽  
Kiyohito Murai ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Signaling Pathway ◽  
Progenitor Cell ◽  
Neural Progenitor Cells ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Dominant Negative ◽  
Neural Cells ◽  
Protein Signaling ◽  
Cell State

Maintaining a balance between self-renewal and differentiation in neural progenitor cells during development is important to ensure that correct numbers of neural cells are generated. We report that the ephrin-B–PDZ-RGS3 signaling pathway functions to regulate this balance in the developing mammalian cerebral cortex. During cortical neurogenesis, expression of ephrin-B1 and PDZ-RGS3 is specifically seen in progenitor cells and is turned off at the onset of neuronal differentiation. Persistent expression of ephrin-B1 and PDZ-RGS3 prevents differentiation of neural progenitor cells. Blocking RGS-mediated ephrin-B1 signaling in progenitor cells through RNA interference or expression of dominant-negative mutants results in differentiation. Genetic knockout of ephrin-B1 causes early cell cycle exit and leads to a concomitant loss of neural progenitor cells. Our results indicate that ephrin-B function is critical for the maintenance of the neural progenitor cell state and that this role of ephrin-B is mediated by PDZ-RGS3, likely via interacting with the noncanonical G protein signaling pathway, which is essential in neural progenitor asymmetrical cell division.

scholarly journals δ-protocadherins control neural progenitor cell proliferation by antagonizing Ryk and Wnt/β-catenin signaling

2020 ◽  
Author(s):  
Sayantanee Biswas ◽  
Michelle R. Emond ◽  
Kurtis Chenoweth ◽  
James D. Jontes
Keyword(s):  
Cell Proliferation ◽  
Nervous System ◽  
Progenitor Cells ◽  
Neural Development ◽  
Progenitor Cell ◽  
Neural Progenitor Cells ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Progenitor Cell Proliferation ◽  
Canonical Wnt

AbstractThe proliferation of neural progenitor cells provides the cellular substrate from which the nervous system is sculpted during development. The δ-protocadherin family of homophilic cell adhesion molecules is essential for the normal development of the nervous system and has been linked to an array of neurodevelopmental disorders. However, the biological functions of δ-protocadherins are not well-defined. Here, we show that the δ-protocadherins regulate proliferation in neural progenitor cells, as lesions in each of six, individual δ-protocadherin genes increase cell division in the developing hindbrain. Moreover, Wnt/β-catenin signaling is upregulated in δ-protocadherin mutants and inhibition of the canonical Wnt pathway occludes the observed proliferation increases. We show that the δ-protocadherins physically associate with the Wnt receptor Ryk, and that Ryk is required for the increased proliferation in protocadherin mutants. Thus, the δ-protocadherins act as novel regulators of Wnt/β-catenin signaling during neural development and could provide lineage-restricted local regulation of canonical Wnt signaling and cell proliferation.

scholarly journals AGS3 and Gαi3 Are Concomitantly Upregulated as Part of the Spindle Orientation Complex during Differentiation of Human Neural Progenitor Cells

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5169
Author(s):  
Jackson L. K. Yip ◽  
Maggie M. K. Lee ◽  
Crystal C. Y. Leung ◽  
Man K. Tse ◽  
Annie S. T. Cheung ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
G Protein ◽  
Pertussis Toxin ◽  
Progenitor Cell ◽  
Neural Progenitor Cells ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Hek293 Cells ◽  
Spindle Orientation ◽  
A Cells

Adult neurogenesis is modulated by many Gi-coupled receptors but the precise mechanism remains elusive. A key step for maintaining the population of neural stem cells in the adult is asymmetric cell division (ACD), a process which entails the formation of two evolutionarily conserved protein complexes that establish the cell polarity and spindle orientation. Since ACD is extremely difficult to monitor in stratified tissues such as the vertebrate brain, we employed human neural progenitor cell lines to examine the regulation of the polarity and spindle orientation complexes during neuronal differentiation. Several components of the spindle orientation complex, but not those of the polarity complex, were upregulated upon differentiation of ENStem-A and ReNcell VM neural progenitor cells. Increased expression of nuclear mitotic apparatus (NuMA), Gαi subunit, and activators of G protein signaling (AGS3 and LGN) coincided with the appearance of a neuronal marker (β-III tubulin) and the concomitant loss of neural progenitor cell markers (nestin and Sox-2). Co-immunoprecipitation assays demonstrated that both Gαi3 and NuMA were associated with AGS3 in differentiated ENStem-A cells. Interestingly, AGS3 appeared to preferentially interact with Gαi3 in ENStem-A cells, and this specificity for Gαi3 was recapitulated in co-immunoprecipitation experiments using HEK293 cells transiently overexpressing GST-tagged AGS3 and different Gαi subunits. Moreover, the binding of Gαi3 to AGS3 was suppressed by GTPγS and pertussis toxin. Disruption of AGS3/Gαi3 interaction by pertussis toxin indicates that AGS3 may recognize the same site on the Gα subunit as G protein-coupled receptors. Regulatory mechanisms controlling the formation of spindle orientation complex may provide novel means to manipulate ACD which in turn may have an impact on neurogenesis.

scholarly journals Neurogenin 1 Mediates Erythropoietin Enhanced Differentiation of Adult Neural Progenitor Cells

2005 ◽  
Vol 26 (4) ◽  
pp. 556-564 ◽  
Author(s):  
Lei Wang ◽  
Zheng G Zhang ◽  
Rui L Zhang ◽  
Zhong X Jiao ◽  
Ying Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Neurite Outgrowth ◽  
Progenitor Cells ◽  
Neuronal Differentiation ◽  
Progenitor Cell ◽  
Neural Progenitor Cells ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Mrna Levels ◽  
Progenitor Cell Proliferation

Proneuronal basic helix–loop–helix (bHLH) transcription factor, neurogenin 1 (Ngn1), regulates neuronal differentiation during development of the cerebral cortex. Akt mediates proneuronal bHLH protein function to promote neuronal differentiation. Here, we show that recombinant human erythropoietin (rhEPO) significantly increased Akt activity and Ngn1 mRNA levels in neural progenitor cells derived from the subventricular zone (SVZ) of adult rat, which was coincident with increases of neural progenitor cell proliferation, differentiation, and neurite outgrowth. Inhibition of Akt activity by the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) inhibitor, LY294002, abolished rhEPO-increased Ngn1 mRNA levels and the effects of rhEPO on neural progenitor cells. In addition, reducing expression of endogenous Ngn1 by means of short-interfering RNA (siRNA) blocked rhEPO-enhanced neuronal differentiation and neurite outgrowth but not rhEPO-increased proliferation. Furthermore, treatment of stroke rat with rhEPO significantly increased Ngn1 mRNA levels in SVZ cells. These data suggest that rhEPO acts as an extracellular molecule that activates the PI3K/Akt pathway, which enhances adult neural progenitor cell proliferation, differentiation, and neurite outgrowth, and Ngn1 is required for Akt-mediated neuronal differentiation and neurite outgrowth.

scholarly journals BRCA1 and ELK-1 regulate Neural Progenitor Cell Fate in the Optic Tectum in response to Visual Experience in Xenopus laevis tadpoles

2021 ◽  
Author(s):  
Lin-Chien Huang ◽  
Haiyan He ◽  
Aaron C. Ta ◽  
Caroline R. McKeown ◽  
Hollis T. Cline
Keyword(s):  
Transcription Factor ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Optic Tectum ◽  
Progenitor Cell ◽  
Visual Experience ◽  
Neural Progenitor Cells ◽  
Neural Progenitor Cell ◽  
Neural Progenitor

In developing Xenopus tadpoles, the optic tectum begins to receive patterned visual input while visuomotor circuits are still undergoing neurogenesis and circuit assembly. This visual input regulates neural progenitor cell fate decisions such that maintaining tadpoles in the dark increases proliferation, expanding the progenitor pool, while visual stimulation promotes neuronal differentiation. To identify regulators of activity-dependent neural progenitor cell fate, we used RNA-Seq to profile the transcriptomes of proliferating neural progenitor cells and newly-differentiated immature neurons. Out of 1,130 differentially expressed (DE) transcripts, we identified six DE transcription factors which are predicted to regulate the majority of the other DE transcripts. Here we focused on Breast cancer 1 (BRCA1) and the ETS-family transcription factor, ELK-1. BRCA1 is known for its role in cancers, but relatively little is known about its potential role in regulating neural progenitor cell fate. ELK-1 is a multifunctional transcription factor which regulates immediate early gene expression. We investigated the effect of BRCA1 and ELK-1 on activity-regulated neurogenesis in the tadpole visual system using in vivo timelapse imaging to monitor the fate of turbo-GFP-expressing SOX2+ neural progenitor cells in the optic tectum. Our longitudinal in vivo imaging analysis shows that knockdown of either BRCA1 or ELK-1 altered the fates of neural progenitor cells, and furthermore that the effects of visual experience on neurogenesis depend on BRCA1 expression, while the effects of visual experience on neuronal differentiation depend on ELK-1 expression. These studies provide insight into the potential mechanisms by which neural activity affects neural progenitor cell fate.

Functionalized self-assembly polypeptide hydrogel scaffold applied in modulation of neural progenitor cell behavior

2016 ◽  
Vol 32 (1) ◽  
pp. 45-60 ◽  
Author(s):  
Mingyong Gao ◽  
Haiyin Tao ◽  
Tao Wang ◽  
Ailin Wei ◽  
Bin He
Keyword(s):  
Extracellular Matrix ◽  
Progenitor Cells ◽  
Self Assembly ◽  
Progenitor Cell ◽  
Neural Progenitor Cells ◽  
Three Dimensional ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Hydrogel Scaffold ◽  
Peptide Hydrogel

Three-dimensional cell culturing provides an appealing biomimetic platform to probe the biological effects of a designed extracellular matrix on the behavior of seeded neural stem or neural progenitor cells. This culturing model serves as an important tool to investigate functional regulators involved in proliferation and differentiation of neural progenitor cells. This study aims to reconstruct a polypeptide hydrogel matrix functionally integrated with cyclo-RGD motif [c(RGDfK)] for initial exploration of neural progenitor cell behavior in three-dimensional culture. Three types of hydrogel scaffolds including Type I collagen, RADA16 self-assembly peptide, and RADA16-c(RGDfK) self-assembly peptide hydrogel were employed to serve as the culturing extracellular matrix of neonatal rat spinal neural progenitor cells. The neural adhesion of functionalized self-assembly peptide hydrogel was acquired prior to its RADA16 counterpart with neural progenitor cell seeding tests. The biophysiological properties of self-assembly peptide hydrogel scaffolds were then detected by scanning electron microscopy and rheology measurements. The biological behavior of embedded neural progenitor cells including cell proliferation and differentiation in three-dimensional niche were analyzed by MTT [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)] tests and immunocytochemistry fluorescence staining. The 1% (w/v) RADA16-c(RGDfK) hydrogel scaffold [R16-c(RGDfK)HS] demonstrated an elastic modulus(312 ± 5.7 Pa) compatible with central neural cells, which significantly facilitated the proliferation of embedded neural progenitor cells. Compared to collagen hydrogel, both RADA16 and RADA16-c(RGDfK) hydrogel scaffold improved the cellular proliferation and neuronal differentiation of neural progenitor cells in a three-dimensional culture model. In order to model neuronal regeneration, introduction of neurotrophin-3 in the differentiation environment significantly increased the neuronal differentiation in which the ratio of Tuj-1-positive cell number increased to 72.5% ± 4.7% in the c(RGDfK)-functionalized three-dimensional matrix environment at 7 days in culture. Collectively, the present R16-c(RGDfK)HS displays excellent central neural biocompatibility and emerges as a promising bioengineered extracellular matrix niche of neural stem or progenitor cells, building a solid foundation for the subsequent in vitro and in vivo studies including neural repair, regeneration, and development.

scholarly journals Histone chaperone HIRA regulates neural progenitor cell proliferation and neurogenesis via β-catenin

2017 ◽  
Vol 216 (7) ◽  
pp. 1975-1992 ◽  
Author(s):  
Yanxin Li ◽  
Jianwei Jiao
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Progenitor Cell ◽  
Neural Progenitor Cells ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Histone Chaperone ◽  
Epigenetic Mechanism ◽  
Progenitor Cell Proliferation ◽  
Early Neurogenesis

Histone cell cycle regulator (HIRA) is a histone chaperone and has been identified as an epigenetic regulator. Subsequent studies have provided evidence that HIRA plays key roles in embryonic development, but its function during early neurogenesis remains unknown. Here, we demonstrate that HIRA is enriched in neural progenitor cells, and HIRA knockdown reduces neural progenitor cell proliferation, increases terminal mitosis and cell cycle exit, and ultimately results in premature neuronal differentiation. Additionally, we demonstrate that HIRA enhances β-catenin expression by recruiting H3K4 trimethyltransferase Setd1A, which increases H3K4me3 levels and heightens the promoter activity of β-catenin. Significantly, overexpression of HIRA, HIRA N-terminal domain, or β-catenin can override neurogenesis abnormities caused by HIRA defects. Collectively, these data implicate that HIRA, cooperating with Setd1A, modulates β-catenin expression and then regulates neurogenesis. This finding represents a novel epigenetic mechanism underlying the histone code and has profound and lasting implications for diseases and neurobiology.

scholarly journals Hydrophilic cell-derived extracellular matrix as a niche to promote adhesion and differentiation of neural progenitor cells

RSC Advances ◽  
2017 ◽  
Vol 7 (72) ◽  
pp. 45587-45594 ◽  
Author(s):  
Lingyan Yang ◽  
Ziyun Jiang ◽  
Linhong Zhou ◽  
Keli Zhao ◽  
Xun Ma ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Basal Forebrain ◽  
Progenitor Cell ◽  
Neural Progenitor Cells ◽  
Cholinergic Neurons ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Basal Forebrain Cholinergic Neurons ◽  
Adhesion Performance ◽  
Excellent Adhesion

Cell-derived extracellular matrix exhibits excellent adhesion performance for neural progenitor cell anchoring and residency, resulting in promoted proliferation of the stem cells to basal forebrain cholinergic neurons.

Transplantation of Neural Progenitor Cells into the Developing Retina of the Brazilian Opossum: An in vivo System for Studying Stem/Progenitor Cell Plasticity

2004 ◽  
Vol 26 (5-6) ◽  
pp. 336-345 ◽  
Author(s):  
D.S. Sakaguchi ◽  
S.J. van Hoffelen ◽  
E. Theusch ◽  
E. Parker ◽  
J. Orasky ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Progenitor Cell ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Cell Plasticity

scholarly journals Neuronal Delamination and Outer Radial Glia Generation in Neocortical Development

2021 ◽  
Vol 8 ◽  
Author(s):  
Ayano Kawaguchi
Keyword(s):  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Radial Glia ◽  
Adherens Junction ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Microtubule Assembly ◽  
Apical Surface ◽  
Neocortical Development ◽  
Outer Radial Glia

During neocortical development, many neuronally differentiating cells (neurons and intermediate progenitor cells) are generated at the apical/ventricular surface by the division of neural progenitor cells (apical radial glial cells, aRGs). Neurogenic cell delamination, in which these neuronally differentiating cells retract their apical processes and depart from the apical surface, is the first step of their migration. Since the microenvironment established by the apical endfeet is crucial for maintaining neuroepithelial (NE)/aRGs, proper timing of the detachment of the apical endfeet is critical for the quantitative control of neurogenesis in cerebral development. During delamination, the microtubule–actin–AJ (adherens junction) configuration at the apical endfeet shows dynamic changes, concurrent with the constriction of the AJ ring at the apical endfeet and downregulation of cadherin expression. This process is mediated by transcriptional suppression of AJ-related molecules and multiple cascades to regulate cell adhesion and cytoskeletal architecture in a posttranscriptional manner. Recent advances have added molecules to the latter category: the interphase centrosome protein AKNA affects microtubule dynamics to destabilize the microtubule–actin–AJ complex, and the microtubule-associated protein Lzts1 inhibits microtubule assembly and activates actomyosin systems at the apical endfeet of differentiating cells. Moreover, Lzts1 induces the oblique division of aRGs, and loss of Lzts1 reduces the generation of outer radial glia (oRGs, also called basal radial glia, bRGs), another type of neural progenitor cell in the subventricular zone. These findings suggest that neurogenic cell delamination, and in some cases oRG generation, could be caused by a spectrum of interlinked mechanisms.

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