期刊
GENES TO CELLS
卷 26, 期 6, 页码 399-410出版社
WILEY
DOI: 10.1111/gtc.12847
关键词
brain morphogenesis; mouse; neocortical development; neural stem cell; neurogenesis; Sonic hedgehog
资金
- Core Research for Evolutional Science and Technology [JPMJCR12W2]
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) [16H06480]
- Japan Society for the Promotion of Science [15K06773, 18K06253]
- Grants-in-Aid for Scientific Research [18K06253, 15K06773] Funding Source: KAKEN
An expanded and folded neocortex is characteristic of higher mammals, including humans and other primates. Shh overexpression during embryogenesis can promote the symmetric proliferative division of NSCs in the neocortical region, resulting in the expansion of the neocortex.
An expanded and folded neocortex is characteristic of higher mammals, including humans and other primates. The neocortical surface area was dramatically enlarged during the course of mammalian brain evolution from lissencephalic to gyrencephalic mammals, and this bestowed higher cognitive functions especially to primates, including humans. In this study, we generated transgenic (Tg) mice in which the expression of Sonic hedgehog (Shh) could be controlled in neural stem cells (NSCs) and neural progenitors by using the Tet-on system. Shh overexpression during embryogenesis promoted the symmetric proliferative division of NSCs in the neocortical region, leading to the expansion of lateral ventricles and tangential extension of the ventricular zone. Moreover, Shh-overexpressing Tg mice showed dramatic expansion of the neocortical surface area and exhibited a wrinkled brain when overexpression was commenced at early stages of neural development. These results indicate that Shh is able to increase the neocortical NSCs and contribute to expansion of the neocortex.
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