Roles of bHLH genes in neural stem cell differentiation

Neural stem cells change their characteristics over time during development: they initially proliferate only and then give rise to neurons first and glial cells later. In the absence of the repressor-type basic helix–loop–helix (bHLH) genes Hes1, Hes3 and Hes5, neural stem cells do not proliferate s...

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Veröffentlicht in:Experimental cell research 2005-06, Vol.306 (2), p.343-348
Hauptverfasser: Kageyama, Ryoichiro, Ohtsuka, Toshiyuki, Hatakeyama, Jun, Ohsawa, Ryosuke
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container_end_page 348
container_issue 2
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container_title Experimental cell research
container_volume 306
creator Kageyama, Ryoichiro
Ohtsuka, Toshiyuki
Hatakeyama, Jun
Ohsawa, Ryosuke
description Neural stem cells change their characteristics over time during development: they initially proliferate only and then give rise to neurons first and glial cells later. In the absence of the repressor-type basic helix–loop–helix (bHLH) genes Hes1, Hes3 and Hes5, neural stem cells do not proliferate sufficiently but prematurely differentiate into neurons and become depleted without making the later born cell types such as astrocytes and ependymal cells. Thus, Hes genes are essential for maintenance of neural stem cells to make cells not only in correct numbers but also in full diversity. Hes genes antagonize the activator-type bHLH genes, which include Mash1, Math and Neurogenin. The activator-type bHLH genes promote the neuronal fate determination and induce expression of Notch ligands such as Delta. These ligands activate Notch signaling and upregulate Hes1 and Hes5 expression in neighboring cells, thereby maintaining these cells undifferentiated. Thus, the activator-type and repressor-type bHLH genes regulate each other, allowing only subsets of cells to undergo differentiation while keeping others to stay neural stem cells. This regulation is essential for generation of complex brain structures of appropriate size, shape and cell arrangement.
doi_str_mv 10.1016/j.yexcr.2005.03.015
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subjects 60 APPLIED LIFE SCIENCES
Animals
bHLH genes
BRAIN
Cell Differentiation
Gene Expression Regulation, Developmental
GENE REGULATION
GENES
Helix-Loop-Helix Motifs - physiology
Hes
Humans
LIGANDS
Mash1
Math
NERVE CELLS
Nerve Tissue Proteins - deficiency
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Neural development
Neural stem cell
Neurogenin
Neuroglia - cytology
Neuroglia - metabolism
Neuroglia - pathology
Neurons - cytology
Notch signaling
Repressor Proteins - genetics
Repressor Proteins - metabolism
STEM CELLS
Stem Cells - cytology
Stem Cells - metabolism
title Roles of bHLH genes in neural stem cell differentiation
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