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Published February 1, 2002 | Published
Journal Article Open

Divergent functions of the proneural genes Mash1 and Ngn2 in the specification of neuronal subtype identity


The neural bHLH genes Mash1 and Ngn2 are expressed in complementary populations of neural progenitors in the central and peripheral nervous systems. Here, we have systematically compared the activities of the two genes during neural development by generating replacement mutations in mice in which the coding sequences ofMash1 and Ngn2 were swapped. Using this approach, we demonstrate that Mash1 has the capacity to respecify the identity of neuronal populations normally derived from Ngn2-expressing progenitors in the dorsal telencephalon and ventral spinal cord. In contrast, misexpression of Ngn2 in Mash1-expressing progenitors does not result in any overt change in neuronal phenotype. Taken together, these results demonstrate that Mash1 and Ngn2 have divergent functions in specification of neuronal subtype identity, with Mash1 having the characteristics of an instructive determinant whereas Ngn2 functions as a permissive factor that must act in combination with other factors to specify neuronal phenotypes. Moreover, the ectopic expression of Ngn2 can rescue the neurogenesis defects of Mash1 null mutants in the ventral telencephalon and sympathetic ganglia but not in the ventral spinal cord and the locus coeruleus, indicating that Mash1 contribution to the specification of neuronal fates varies greatly in different lineages, presumably depending on the presence of other determinants of neuronal identity.

Additional Information

© 2002 by Cold Spring Harbor Laboratory Press. Six months after the full-issue publication date, the Article will be distributed under a Creative Commons CC-BY-NC License (Attribution-NonCommercial 4.0 International License, http://creativecommons.org/licenses/by-nc/4.0/). Received August 27, 2001; revised version accepted December 11, 2001. We thank members of the lab for their advice during the progress of the work and Jean-François Brunet for his critical comments on the manuscript. We also thank Jean-Luc Vonesch and Didier Hentsch for help with confocal microscopy, and Marianne LeMeur and the transgenic facility staff for the generation of the knock-in mouse strains. We thank J. Ericson, S. Hodge, C.C. Hui, R.R. McInnes, S. Pfaff, and J. Rubenstein for the gifts of cDNAs and antibodies. The monoclonal antibodies Pax6, 74.5A5, 40.2D6, 4G11, 81.5C10, and 67.4E12, developed by A. Kawakami, T.M. Jessell, and S. Brenner-Morton were obtained from the Developmental Studies Hybridoma Bank maintained by the Iowa University, Department of Biological Sciences. C.P was supported by long term postdoctoral fellowships from the Spanish Ramón Areces Foundation and from the EMBO, C.S. by long term postdoctoral fellowships from the Human Frontiers Science Program and the Medical Research Council of Canada, and R. S. by the Italian Telethon Foundation and the European Community TRM Program. Note the change of name from Carol Fode to Carol Schuurmans. This work was supported by grants from the European Community "Quality of Life and Management of Living Resources" Research and Technological Development Program, the Human Frontiers Science Program, the Association pour la Recherche sur le Cancer and the Ministère de l'Enseignement et de la Recherche to F.G. and by institutional funds from INSERM, CNRS, and Hôpital Universitaire de Strasbourg. The publication costs of this article were defrayed in part by payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

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