期刊
JOURNAL OF NEUROSCIENCE
卷 27, 期 22, 页码 5926-5935出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1538-07.2007
关键词
E2F4; cell cycle; Sonic hedgehog; neural precursors; neural patterning; telencephalon
Early forebrain development is characterized by extensive proliferation of neural precursors coupled with complex structural transformations; however, little is known regarding the mechanisms by which these processes are integrated. Here, we show that deficiency of the cell cycle regulatory protein, E2F4, results in the loss of ventral telencephalic structures and impaired self- renewal of neural precursor cells. The mechanism underlying aberrant ventral patterning lies in a dramatic loss of Sonic hedgehog ( Shh) expression specifically in this region. The E2F4- deficient phenotype can be recapitulated by interbreeding mice heterozygous for E2F4 with those lacking one allele of Shh, suggesting a genetic interaction between these pathways. Treatment of E2F4- deficient cells with a Hh agonist rescues stem cell self- renewal and cells expressing the homeodomain proteins that specify the ventral telencephalic structures. Finally, we show that E2F4 deficiency results in impaired activity of Shh forebrain- specific enhancers. In conclusion, these studies establish a novel requirement for the cell cycle regulatory protein, E2F4, in the development of the ventral telencephalon.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据