scholarly journals Cdk2 is critical for proliferation and self-renewal of neural progenitor cells in the adult subventricular zone

2007 ◽  
Vol 179 (6) ◽  
pp. 1231-1245 ◽  
Author(s):  
Beata Jablonska ◽  
Adan Aguirre ◽  
Renaud Vandenbosch ◽  
Shibeshih Belachew ◽  
Cyril Berthet ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Progenitor Cells ◽  
Subventricular Zone ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Wild Type ◽  
Compensatory Mechanisms ◽  
Self Renewal ◽  
Significant Difference ◽  
Progenitor Cell Proliferation

We investigated the function of cyclin-dependent kinase 2 (Cdk2) in neural progenitor cells during postnatal development. Chondroitin sulfate proteoglycan (NG2)–expressing progenitor cells of the subventricular zone (SVZ) show no significant difference in density and proliferation between Cdk2−/− and wild-type mice at perinatal ages and are reduced only in adult Cdk2−/− mice. Adult Cdk2−/− SVZ cells in culture display decreased self-renewal capacity and enhanced differentiation. Compensatory mechanisms in perinatal Cdk2−/− SVZ cells, which persist until postnatal day 15, involve increased Cdk4 expression that results in retinoblastoma protein inactivation. A subsequent decline in Cdk4 activity to wild-type levels in postnatal day 28 Cdk2−/− cells coincides with lower NG2+ proliferation and self-renewal capacity similar to adult levels. Cdk4 silencing in perinatal Cdk2−/− SVZ cells abolishes Cdk4 up-regulation and reduces cell proliferation and self- renewal to adult levels. Conversely, Cdk4 overexpression in adult SVZ cells restores proliferative capacity to wild-type levels. Thus, although Cdk2 is functionally redundant in perinatal SVZ, it is important for adult progenitor cell proliferation and self-renewal through age-dependent regulation of Cdk4.

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 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 Coupling of Angiogenesis and Neurogenesis in Cultured Endothelial Cells and Neural Progenitor Cells after Stroke

2007 ◽  
Vol 28 (4) ◽  
pp. 764-771 ◽  
Author(s):  
Hua Teng ◽  
Zheng Gang Zhang ◽  
Lei Wang ◽  
Rui Lan Zhang ◽  
Li Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Progenitor Cells ◽  
Subventricular Zone ◽  
Neural Progenitor Cells ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Vascular Endothelial ◽  
Cerebral Endothelial Cells ◽  
Progenitor Cell Proliferation ◽  
Endothelial Growth Factor

Angiogenesis and neurogenesis are coupled processes. Using a coculture system, we tested the hypothesis that cerebral endothelial cells activated by ischemia enhance neural progenitor cell proliferation and differentiation, while neural progenitor cells isolated from the ischemic subventricular zone promote angiogenesis. Coculture of neural progenitor cells isolated from the subventricular zone of the adult normal rat with cerebral endothelial cells isolated from the stroke boundary substantially increased neural progenitor cell proliferation and neuronal differentiation and reduced astrocytic differentiation. Conditioned medium harvested from the stroke neural progenitor cells promoted capillary tube formation of normal cerebral endothelial cells. Blockage of vascular endothelial growth factor receptor 2 suppressed the effect of the endothelial cells activated by stroke on neurogenesis as well as the effect of the supernatant obtained from stroke neural progenitor cells on angiogenesis. These data suggest that angiogenesis couples to neurogenesis after stroke and vascular endothelial growth factor likely mediates this coupling.

scholarly journals Isolation of Neural Progenitor Cells From the Human Adult Subventricular Zone Based on Expression of the Cell Surface Marker CD271

2014 ◽  
Vol 3 (4) ◽  
pp. 470-480 ◽  
Author(s):  
Miriam E. van Strien ◽  
Jacqueline A. Sluijs ◽  
Brent A. Reynolds ◽  
Dennis A. Steindler ◽  
Eleonora Aronica ◽  
...  
Keyword(s):  
Cell Surface ◽  
Progenitor Cells ◽  
Subventricular Zone ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Surface Marker ◽  
Cell Surface Marker ◽  
Human Adult

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.

P2X7 receptors at adult neural progenitor cells of the mouse subventricular zone

2013 ◽  
Vol 73 ◽  
pp. 122-137 ◽  
Author(s):  
Nanette Messemer ◽  
Christin Kunert ◽  
Marcus Grohmann ◽  
Helga Sobottka ◽  
Karen Nieber ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Subventricular Zone ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
P2x7 Receptors
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