Botch Promotes Neurogenesis by Antagonizing Notch

作者：Chi Zhikai; Zhang Jianmin; Tokunaga Akinori; Harraz Maged M; Byrne Sean T; Dolinko Andrew; Xu Jing; Blackshaw Seth; Gaiano Nicholas; Dawson Ted M^*; Dawson Valina L

来源：Developmental Cell, 2012, 22(4): 707-720.

DOI：10.1016/j.devcel.2012.02.011

Regulation of self-renewal and differentiation of neural stem cells is still poorly understood. Here we investigate the role of a developmentally expressed protein, Botch, which blocks Notch, in neocortical development. Downregulation of Botch in vivo leads to cellular retention in the ventricular and subventricular zones, whereas overexpression of Botch drives neural stem cells into the intermediate zone and cortical plate. In vitro neurosphere and differentiation assays indicate that Botch regulates neurogenesis by promoting neuronal differentiation. Botch prevents cell surface presentation of Notch by inhibiting the Si furin-like cleavage of Notch, maintaining Notch in the immature full-length form. Understanding the function of Botch expands our knowledge regarding both the regulation of Notch signaling and the complex signaling mediating neuronal development.

• 出版日期2012-4-17