scholarly journals NCAM regulates temporal specification of neural progenitor cells via profilin2 during corticogenesis

2019 ◽  
Vol 219 (1) ◽  
Author(s):  
Rui Huang ◽  
De-Juan Yuan ◽  
Shao Li ◽  
Xue-Song Liang ◽  
Yue Gao ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Cortical Neurons ◽  
Actin Polymerization ◽  
Molecular Mechanisms ◽  
Neural Progenitor Cells ◽  
Cortical Development ◽  
Neural Progenitor ◽  
Neural Cell Adhesion ◽  
Fate Decision ◽  
Temporal Specification

The development of cerebral cortex requires spatially and temporally orchestrated proliferation, migration, and differentiation of neural progenitor cells (NPCs). The molecular mechanisms underlying cortical development are, however, not fully understood. The neural cell adhesion molecule (NCAM) has been suggested to play a role in corticogenesis. Here we show that NCAM is dynamically expressed in the developing cortex. NCAM expression in NPCs is highest in the neurogenic period and declines during the gliogenic period. In mice bearing an NPC-specific NCAM deletion, proliferation of NPCs is reduced, and production of cortical neurons is delayed, while formation of cortical glia is advanced. Mechanistically, NCAM enhances actin polymerization in NPCs by interacting with actin-associated protein profilin2. NCAM-dependent regulation of NPCs is blocked by mutations in the profilin2 binding site. Thus, NCAM plays an essential role in NPC proliferation and fate decision during cortical development by regulating profilin2-dependent actin polymerization.

scholarly journals KIF20A/MKLP2 regulates the division modes of neural progenitor cells during cortical development

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Anqi Geng ◽  
Runxiang Qiu ◽  
Kiyohito Murai ◽  
Jiancheng Liu ◽  
Xiwei Wu ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Cortical Development ◽  
Neural Progenitor

scholarly journals SEPT7 Interacts with KIF20A and Regulates the Proliferative State of Neural Progenitor Cells During Cortical Development

2019 ◽  
Vol 30 (5) ◽  
pp. 3030-3043 ◽  
Author(s):  
Runxiang Qiu ◽  
Qiu Runxiang ◽  
Anqi Geng ◽  
Jiancheng Liu ◽  
C Wilson Xu ◽  
...  
Keyword(s):  
Cell Division ◽  
Progenitor Cells ◽  
Neuronal Differentiation ◽  
Cell Fate ◽  
Neural Progenitor Cells ◽  
Cortical Development ◽  
Neural Progenitor ◽  
Mammalian Brain ◽  
Additional Cell ◽  
A Cell

Abstract Balanced proliferation and differentiation of neural progenitor cells (NPCs) are critical for brain development, but how the process is regulated and what components of the cell division machinery is involved are not well understood. Here we report that SEPT7, a cell division regulator originally identified in Saccharomyces cerevisiae, interacts with KIF20A in the intercellular bridge of dividing NPCs and plays an essential role in maintaining the proliferative state of NPCs during cortical development. Knockdown of SEPT7 in NPCs results in displacement of KIF20A from the midbody and early neuronal differentiation. NPC-specific inducible knockout of Sept7 causes early cell cycle exit, precocious neuronal differentiation, and ventriculomegaly in the cortex, but surprisingly does not lead to noticeable cytokinesis defect. Our data uncover an interaction of SEPT7 and KIF20A during NPC divisions and demonstrate a crucial role of SEPT7 in cell fate determination. In addition, this study presents a functional approach for identifying additional cell fate regulators of the mammalian brain.

scholarly journals IGF-I instructs multipotent adult neural progenitor cells to become oligodendrocytes

2004 ◽  
Vol 164 (1) ◽  
pp. 111-122 ◽  
Author(s):  
Jenny Hsieh ◽  
James B. Aimone ◽  
Brian K. Kaspar ◽  
Tomoko Kuwabara ◽  
Kinichi Nakashima ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Single Molecule ◽  
Molecular Mechanisms ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Protein Signaling ◽  
Adult Rat ◽  
Morphogenetic Protein ◽  
Modeling Analysis ◽  
Igf I

Adult multipotent neural progenitor cells can differentiate into neurons, astrocytes, and oligodendrocytes in the mammalian central nervous system, but the molecular mechanisms that control their differentiation are not yet well understood. Insulin-like growth factor I (IGF-I) can promote the differentiation of cells already committed to an oligodendroglial lineage during development. However, it is unclear whether IGF-I affects multipotent neural progenitor cells. Here, we show that IGF-I stimulates the differentiation of multipotent adult rat hippocampus-derived neural progenitor cells into oligodendrocytes. Modeling analysis indicates that the actions of IGF-I are instructive. Oligodendrocyte differentiation by IGF-I appears to be mediated through an inhibition of bone morphogenetic protein signaling. Furthermore, overexpression of IGF-I in the hippocampus leads to an increase in oligodendrocyte markers. These data demonstrate the existence of a single molecule, IGF-I, that can influence the fate choice of multipotent adult neural progenitor cells to an oligodendroglial lineage.

scholarly journals RhoG Promotes Neural Progenitor Cell Proliferation in Mouse Cerebral Cortex

2009 ◽  
Vol 20 (23) ◽  
pp. 4941-4950 ◽  
Author(s):  
Satoshi Fujimoto ◽  
Manabu Negishi ◽  
Hironori Katoh
Keyword(s):  
Molecular Mechanisms ◽  
Neural Progenitor Cells ◽  
Ventricular Zone ◽  
Cortical Development ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Brdu Incorporation ◽  
Progenitor Cell Proliferation

In early cortical development, neural progenitor cells (NPCs) expand their population in the ventricular zone (VZ), and produce neurons. Although a series of studies have revealed the process of neurogenesis, the molecular mechanisms regulating NPC proliferation are still largely unknown. Here we found that RhoG, a member of Rho family GTPases, was expressed in the VZ at early stages of cortical development. Expression of constitutively active RhoG promoted NPC proliferation and incorporation of bromodeoxyuridine (BrdU) in vitro, and the proportion of Ki67-positive cells in vivo. In contrast, knockdown of RhoG by RNA interference suppressed the proliferation, BrdU incorporation, and the proportion of Ki67-positive cells in NPCs. However, knockdown of RhoG did not affect differentiation and survival of NPC. The RhoG-induced promotion of BrdU incorporation required phosphatidylinositol 3-kinase (PI3K) activity but not the interaction with ELMO. Taken together, these results indicate that RhoG promotes NPC proliferation through PI3K in cortical development.

Lipid rafts enriched in phosphatidylglucoside direct astroglial differentiation by regulating tyrosine kinase activity of epidermal growth factor receptors

2009 ◽  
Vol 419 (3) ◽  
pp. 565-575 ◽  
Author(s):  
Masami O. Kinoshita ◽  
Shigeki Furuya ◽  
Shinya Ito ◽  
Yoko Shinoda ◽  
Yasuhiro Yamazaki ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Progenitor Cells ◽  
Lipid Rafts ◽  
Neural Progenitor Cells ◽  
Cortical Development ◽  
Neural Progenitor ◽  
Janus Kinase ◽  
Epidermal Growth

Membrane lipid rafts provide a specialized microenvironment enriched with sphingolipids and phospholipids containing saturated fatty acids and serve as a platform for various intracellular signalling pathways. PtdGlc (phosphatidylglucoside) is a type of glycophospholipid localized in the outer leaflet of the plasma membrane. Owing to PtdGlc's unique fatty acid composition, exclusively composed of C18:0 at sn-1 and C20:0 at sn-2 of the glycerol backbone, it tends to form PGLRs (PtdGlc-enriched lipid rafts). Previously, we demonstrated that PGLRs reside on the cell surface of astroglial cells from fetal rat brain [Nagatsuka, Horibata, Yamazaki, Kinoshita, Shinoda, Hashikawa, Koshino, Nakamura and Hirabayashi (2006) Biochemistry 45, 8742–8750]. In the present study, we observed PGLRs in astroglial lineage cells at mid-embryonic to early-postnatal stages of developing mouse cortex. This suggests that PGLRs are developmentally correlated with astroglial differentiation during fetal cortical development. Our cell culture studies with multipotent neural progenitor cells prepared from fetal mouse telencephalon demonstrated that treatment with EGF (epidermal growth factor) or anti-PtdGlc antibody caused recruitment of EGFRs (EGF receptors) into lipid raft compartments, leading to activation of EGFRs. Moreover, the activation of EGFRs by antibody triggered downstream tyrosine kinase signalling and induced marked GFAP (glial fibrillary acidic protein) expression via the JAK (Janus kinase)/STAT (signal transducer and activator of transcription) signalling pathway. These findings strongly suggest that PGLRs are physiologically coupled to activated EGFRs on neural progenitor cells during fetal cortical development, and thereby play a distinct role in mediating astrogliogenesis.

scholarly journals Dual Role of Rbpj in the Maintenance of Neural Progenitor Cells and Neuronal Migration in Cortical Development

2020 ◽  
Vol 30 (12) ◽  
pp. 6444-6457
Author(s):  
Alexander I Son ◽  
Shahid Mohammad ◽  
Toru Sasaki ◽  
Seiji Ishii ◽  
Satoshi Yamashita ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Notch Signaling ◽  
Progenitor Cells ◽  
Knockout Mice ◽  
Neural Progenitor Cells ◽  
Cortical Development ◽  
Neural Progenitor ◽  
Dual Role

Abstract The development of the cerebral cortex is directed by a series of methodically precise events, including progenitor cell proliferation, neural differentiation, and cell positioning. Over the past decade, many studies have demonstrated the critical contributions of Notch signaling in neurogenesis, including that in the developing telencephalon. However, in vivo evidence for the role of Notch signaling in cortical development still remains limited partly due to the redundant functions of four mammalian Notch paralogues and embryonic lethality of the knockout mice. Here, we utilized the conditional deletion and in vivo gene manipulation of Rbpj, a transcription factor that mediates signaling by all four Notch receptors, to overcome these challenges and examined the specific roles of Rbpj in cortical development. We report severe structural abnormalities in the embryonic and postnatal cerebral cortex in Rbpj conditional knockout mice, which provide strong in vivo corroboration of previously reported functions of Notch signaling in neural development. Our results also provide evidence for a novel dual role of Rbpj in cell type-specific regulation of two key developmental events in the cerebral cortex: the maintenance of the undifferentiated state of neural progenitor cells, and the radial and tangential allocation of neurons, possibly through stage-dependent differential regulation of Ngn1.

scholarly journals Comparative Microarray Analysis of Proliferating and Differentiating Murine ENS Progenitor Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Peter Helmut Neckel ◽  
Roland Mohr ◽  
Ying Zhang ◽  
Bernhard Hirt ◽  
Lothar Just
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Developmental Dysplasia ◽  
Cellular Mechanisms ◽  
Differentiation Markers ◽  
Early Differentiation

Postnatal neural progenitor cells of the enteric nervous system are a potential source for future cell replacement therapies of developmental dysplasia like Hirschsprung’s disease. However, little is known about the molecular mechanisms driving the homeostasis and differentiation of this cell pool. In this work, we conducted Affymetrix GeneChip experiments to identify differences in gene regulation between proliferation and early differentiation of enteric neural progenitors from neonatal mice. We detected a total of 1333 regulated genes that were linked to different groups of cellular mechanisms involved in cell cycle, apoptosis, neural proliferation, and differentiation. As expected, we found an augmented inhibition in the gene expression of cell cycle progression as well as an enhanced mRNA expression of neuronal and glial differentiation markers. We further found a marked inactivation of the canonical Wnt pathway after the induction of cellular differentiation. Taken together, these data demonstrate the various molecular mechanisms taking place during the proliferation and early differentiation of enteric neural progenitor cells.

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