Roles of bHLH genes in neural stem cell differentiation

被引:430
作者
Kageyama, R [1 ]
Ohtsuka, T [1 ]
Hatakeyama, J [1 ]
Ohsawa, R [1 ]
机构
[1] Kyoto Univ, Inst Virus Res, Sakyo Ku, Kyoto 6068507, Japan
关键词
bHLH genes; neural stem cell; neural development; Hes; Mash1; Math; neurogenin; notch signaling;
D O I
10.1016/j.yexcr.2005.03.015
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:343 / 348
页数:6
相关论文
共 48 条
[41]   Divergent functions of the proneural genes Mash1 and Ngn2 in the specification of neuronal subtype identity [J].
Parras, CM ;
Schuurmans, C ;
Scardigli, R ;
Kim, J ;
Anderson, DJ ;
Guillemot, F .
GENES & DEVELOPMENT, 2002, 16 (03) :324-338
[42]   Basic helix-loop-helix factors in cortical development [J].
Ross, SE ;
Greenberg, ME ;
Stiles, CD .
NEURON, 2003, 39 (01) :13-25
[43]   The basic helix-loop-helix genes Hesr1/Hey1 and Hesr2/Hey2 regulate maintenance of neural precursor cells in the brain [J].
Sakamoto, M ;
Hirata, H ;
Ohtsuka, T ;
Bessho, Y ;
Kageyama, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (45) :44808-44815
[44]   2 MAMMALIAN HELIX LOOP HELIX FACTORS STRUCTURALLY RELATED TO DROSOPHILA HAIRY AND ENHANCER OF SPLIT [J].
SASAI, Y ;
KAGEYAMA, R ;
TAGAWA, Y ;
SHIGEMOTO, R ;
NAKANISHI, S .
GENES & DEVELOPMENT, 1992, 6 (12B) :2620-2634
[45]   Notch and presenilin: Regulated intramembrane proteolysis links development and degeneration [J].
Selkoe, D ;
Kopan, R .
ANNUAL REVIEW OF NEUROSCIENCE, 2003, 26 :565-597
[46]   Neurogenin promotes neurogenesis and inhibits glial differentiation by independent mechanisms [J].
Sun, Y ;
Nadal-Vicens, M ;
Misono, S ;
Lin, MZ ;
Zubiaga, A ;
Hua, XX ;
Fan, GP ;
Greenberg, ME .
CELL, 2001, 104 (03) :365-376
[47]   Mammalian achaete-scute and atonal homologs regulate neuronal versus glial fate determination in the central nervous system [J].
Tomita, K ;
Moriyoshi, K ;
Nakanishi, S ;
Guillemot, F ;
Kageyama, R .
EMBO JOURNAL, 2000, 19 (20) :5460-5472
[48]   The bHLH transcription factor Olig2 promotes oligodendrocyte differentiation in collaboration with Nkx2.2 [J].
Zhou, Q ;
Choi, G ;
Anderson, DJ .
NEURON, 2001, 31 (05) :791-807