Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 9922K) PDF+supp data (14356K) PPT slides of all figures Supplemental Material Index Correction (v184,p335) Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Nagao, M. Articles by Nakafuku, M. Search for Related Content PubMed PubMed Citation Articles by Nagao, M. Articles by Nakafuku, M. Social Bookmarking                            What's this?

Coordinated control of self-renewal and differentiation of neural stem cells by Myc and the p19^ARF–p53 pathway

¹ Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH 45229
² Department of Pediatrics and ³ Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH 45267
⁴ Divison of Cell Biology, Deutsches Krebsforschungszentrum (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany
⁵ Heidelberg Institute for Stem Cell Technologies and Experimental Medicine (HI-STEM), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany

Correspondence to Masato Nakafuku: masato.nakafuku{at}cchmc.org

The modes of proliferation and differentiation of neural stem cells (NSCs) are coordinately controlled during development, but the underlying mechanisms remain largely unknown. In this study, we show that the protooncoprotein Myc and the tumor suppressor p19^ARF regulate both NSC self-renewal and their neuronal and glial fate in a developmental stage–dependent manner. Early-stage NSCs have low p19^ARF expression and retain a high self-renewal and neurogenic capacity, whereas late-stage NSCs with higher p19^ARF expression possess a lower self-renewal capacity and predominantly generate glia. Overexpression of Myc or inactivation of p19^ARF reverts the properties of late-stage NSCs to those of early-stage cells. Conversely, inactivation of Myc or forced p19^ARF expression attenuates self-renewal and induces precocious gliogenesis through modulation of the responsiveness to gliogenic signals. These actions of p19^ARF in NSCs are mainly mediated by p53. We propose that opposing actions of Myc and the p19^ARF–p53 pathway have important functions in coordinated developmental control of self-renewal and cell fate choices in NSCs.

© 2008 Nagao et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents