Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Dev Cell. 2012 Apr 17;22(4):707-20. doi: 10.1016/j.devcel.2012.02.011. Epub 2012 Mar 22.
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 S1 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.
神经干细胞自我更新和分化的调控仍知之甚少。在这里，我们研究了一种发育表达蛋白 Botch 的作用，它可以阻断 Notch，在新皮层发育中起作用。体内下调 Botch 导致细胞在脑室和室下区滞留，而过表达 Botch 则将神经干细胞驱动到中间区和皮质板。体外神经球和分化试验表明，Botch 通过促进神经元分化来调节神经发生。Botch 通过抑制 Notch 的 S1 类枯草杆菌蛋白酶样切割来阻止 Notch 的细胞表面呈现，从而保持 Notch 处于不成熟的全长形式。了解 Botch 的功能扩展了我们对 Notch 信号转导调控以及介导神经元发育的复杂信号转导的认识。
