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Dev Cell. 2012 Apr 17;22(4):707-20. doi: 10.1016/j.devcel.2012.02.011. Epub 2012 Mar 22.

Botch promotes neurogenesis by antagonizing Notch.

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  • 1Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

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.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
22445366
[PubMed - indexed for MEDLINE]
PMCID:
PMC3331935
Free PMC Article

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