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Regulation of neural progenitor cell state by ephrin-B
Correspondence to Qiang Lu: qlu{at}coh.org
Maintaining a balance between self-renewal and differentiation in neural progenitor cells during development is important to ensure that correct numbers of neural cells are generated. We report that the ephrin-B–PDZ-RGS3 signaling pathway functions to regulate this balance in the developing mammalian cerebral cortex. During cortical neurogenesis, expression of ephrin-B1 and PDZ-RGS3 is specifically seen in progenitor cells and is turned off at the onset of neuronal differentiation. Persistent expression of ephrin-B1 and PDZ-RGS3 prevents differentiation of neural progenitor cells. Blocking RGS-mediated ephrin-B1 signaling in progenitor cells through RNA interference or expression of dominant-negative mutants results in differentiation. Genetic knockout of ephrin-B1 causes early cell cycle exit and leads to a concomitant loss of neural progenitor cells. Our results indicate that ephrin-B function is critical for the maintenance of the neural progenitor cell state and that this role of ephrin-B is mediated by PDZ-RGS3, likely via interacting with the noncanonical G protein signaling pathway, which is essential in neural progenitor asymmetrical cell division.
Alice Davy's present address is Centre de Biologie du Développement, Université de Toulouse/Centre National de la Recherche Scientifique, 31062 Toulouse cedex 9, France.
Abbreviations used in this paper: BrdU, bromodeoxyuridine; CDS, coding sequence; CP, cortical plate; DCX, doublecortin; E, embryonic day; IZ, intermediate zone; p-H3+, phospho–Histone H3+; RGS, Regulator of G protein Signaling; shRNA, short hairpin RNA; SVZ, subventricular zone; VZ, ventricular zone.
© 2008 Qiu 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/).
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