Ebf gene function is required for coupling neuronal differentiation and cell cycle exit
Author:
Garcia-Dominguez Mario1, Poquet Christophe1, Garel Sonia1, Charnay Patrick1
Affiliation:
1. Unité 368 de l'Institut National de la Santé et de la Recherche Médicale, Ecole Normale Supérieure, 46 rue d'Ulm,75230 Paris Cedex 05, France
Abstract
Helix-loop-helix transcription factors of the Ebf/Olf1 family have previously been implicated in the control of neurogenesis in the central nervous system in both Xenopus laevis and the mouse, but their precise roles have remained unclear. We have characterised two family members in the chick, and have performed a functional analysis by gain- and loss-of-function experiments. This study revealed several specific roles for Ebf genes in the spinal cord and hindbrain regions of higher vertebrates, and enabled their precise positioning along the neurogenic cascade.During neurogenesis, cell cycle exit appears to be tightly coupled to migration to the mantle layer and to neuronal differentiation. We show that antagonizing Ebf gene activity allows the uncoupling of these processes. Ebf gene function is necessary to initiate neuronal differentiation and migration toward the mantle layer in neuroepithelial progenitors, but it is not required for cell cycle exit. Ebf genes therefore appear to be master controllers of neuronal differentiation and migration, coupling them to cell cycle exit and earlier steps of neurogenesis.Mutual activation between proneural and Ebf genes suggests that besides their involvement in the engagement of differentiation, Ebf genes may also participate in the stabilisation of the committed state. Finally,gain-of-function data raise the possibility that, in addition to these general roles, Ebf genes may be involved in neuronal subtype specification in particular regions of the CNS.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Reference50 articles.
1. Bally-Cuif, L., Dubois, L. and Vincent, A.(1998). Molecular cloning of Zcoe2, the zebrafish homolog of Xenopus Xcoe2 and mouse EBF-2, and its expression during primary neurogenesis. Mech. Dev.77,85-90. 2. Begley, C. G., Lipkowitz, S., Gobel, V., Mahon, K. A., Bertness,V., Green, A. R., Gough, N. M. and Kirsch, I. R.(1992). Molecular characterization of NSCL, a gene encoding a helix-loop-helix protein expressed in the developing nervous system. Proc. Natl. Acad. Sci. USA89, 38-42. 3. Bertrand, N., Castro, D. S. and Guillemot, F.(2002). Proneural genes and the specification of neural cell types. Nat. Rev. Neurosci.3, 517-530. 4. Corradi, A., Croci, L., Broccoli, V., Zecchini, S., Previtali,S., Wurst, W., Amadio, S., Maggi, R., Quattrini, A. and Consalez, G. G. (2003). Hypogonadotropic hypogonadism and peripheral neuropathy in Ebf2-null mice. Development130,401-410. 5. Crozatier, M., Valle, D., Dubois, L., Ibnsouda, S. and Vincent,A. (1996). Collier, a novel regulator of Drosophila head development, is expressed in a single mitotic domain. Curr. Biol.6,707-718.
Cited by
113 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|