Correction: The Niche Factor Syndecan-1 Regulates the Maintenance and Proliferation of Neural Progenitor Cells during Mammalian Cortical Development

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.

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

Cerebral Cortex ◽

10.1093/cercor/bhz292 ◽

2019 ◽

Vol 30 (5) ◽

pp. 3030-3043 ◽

Cited By ~ 2

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.

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

Biochemical Journal ◽

10.1042/bj20081896 ◽

2009 ◽

Vol 419 (3) ◽

pp. 565-575 ◽

Cited By ~ 30

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.

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

Cerebral Cortex ◽

10.1093/cercor/bhaa206 ◽

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.

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Roots of the Malformations of Cortical Development in the Cell Biology of Neural Progenitor Cells

Frontiers in Neuroscience ◽

10.3389/fnins.2021.817218 ◽

2022 ◽

Vol 15 ◽

Author(s):

Chiara Ossola ◽

Nereo Kalebic

Keyword(s):

Cerebral Cortex ◽

Progenitor Cells ◽

Neural Progenitor Cells ◽

Cortical Development ◽

Neural Progenitor ◽

Autism Spectrum ◽

Model Systems ◽

Cortical Plate ◽

Malformations Of Cortical Development ◽

Brain Functions

The cerebral cortex is a structure that underlies various brain functions, including cognition and language. Mammalian cerebral cortex starts developing during the embryonic period with the neural progenitor cells generating neurons. Newborn neurons migrate along progenitors’ radial processes from the site of their origin in the germinal zones to the cortical plate, where they mature and integrate in the forming circuitry. Cell biological features of neural progenitors, such as the location and timing of their mitoses, together with their characteristic morphologies, can directly or indirectly regulate the abundance and the identity of their neuronal progeny. Alterations in the complex and delicate process of cerebral cortex development can lead to malformations of cortical development (MCDs). They include various structural abnormalities that affect the size, thickness and/or folding pattern of the developing cortex. Their clinical manifestations can entail a neurodevelopmental disorder, such as epilepsy, developmental delay, intellectual disability, or autism spectrum disorder. The recent advancements of molecular and neuroimaging techniques, along with the development of appropriate in vitro and in vivo model systems, have enabled the assessment of the genetic and environmental causes of MCDs. Here we broadly review the cell biological characteristics of neural progenitor cells and focus on those features whose perturbations have been linked to MCDs.

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The T-type Ca2+ Channel Cav3.2 Regulates Differentiation of Neural Progenitor Cells during Cortical Development via Caspase-3

Neuroscience ◽

10.1016/j.neuroscience.2019.01.015 ◽

2019 ◽

Vol 402 ◽

pp. 78-89 ◽

Cited By ~ 1

Author(s):

Paola Rebellato ◽

Dagmara Kaczynska ◽

Shigeaki Kanatani ◽

Ibrahim Al Rayyes ◽

Songbai Zhang ◽

...

Keyword(s):

Progenitor Cells ◽

Neural Progenitor Cells ◽

Caspase 3 ◽

Cortical Development ◽

Neural Progenitor

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RalGAPα1is dispensable for embryonic cortical morphogenesisin mice

10.21203/rs.3.rs-408297/v1 ◽

2021 ◽

Author(s):

Yingqian Xia ◽

Chaoli Huang ◽

Sangsang Zhu ◽

Qiaoli Chen ◽

Guiquan Chen ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Brain Development ◽

Progenitor Cells ◽

Neural Progenitor Cells ◽

Cortical Development ◽

Neural Progenitor ◽

Conditional Knockout ◽

Deletion Syndrome ◽

The Central Nervous System

Abstract Background: Cortical morphogenesis is a complex process and involves a large number of genes. RalGAPα1 gene (also called Tulip1 ), mapped to chromosome 14q13.2, is a candidate gene for the 14q13 deletion syndrome associated with delayed brain development. However, it remains unknown whether RalGAPα1 directly regulates cortical development. Methods: To address the above question, we generated neural progenitor cells (NPCs) specific RalGAPα1 conditional knockout (cKO) mice through crossing RalGAPα1 f/f to Nestin-Cre transgenic (Tg) mice in which the Cre recombinase is expressed in neural progenitor cells and derived neurons in the central nervous system (CNS) since very early stage of development. Morphological, biochemistry and immunohistochemistry (IHC) methods were used to evaluate brain development. Results: We found that the brain size, shape and cortical laminations were comparable between control and RalGAPα1 cKO mice. Moreover, the populations and proliferations of NPCs in the ventricular and subventricular zones were not different between control and RalGAPα1 cKO cortices. Conclusions: Inactivation of RalGAPα1 in the central nervous system in murine model does not significantly affect the embryonic cortical development. Keywords: RalGAPα1 ; cortical development; neural progenitor cells; neurodevelopmental disease

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Analysis of the Gli3, Olig2, Nkx6-1 and Nkx2-2 cistromes in mouse 1° neural progenitor cells.

Signaling Pathways Project Datasets ◽

10.1621/ahlzxmjtxq ◽

2019 ◽

Author(s):

Y Nishi

Keyword(s):

Progenitor Cells ◽

Neural Progenitor Cells ◽

Neural Progenitor

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