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

  1. Carlos M. Parras1,4,
  2. Carol Schuurmans1,3,4,
  3. Raffaella Scardigli1,
  4. Jaesang Kim2,
  5. David J. Anderson2, and
  6. François Guillemot1,5
  1. 1Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur, 67404 Illkirch cedex, C.U. de Strasbourg, France; 2Division of Biology 216-76, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125, USA

Abstract

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 fromNgn2-expressing progenitors in the dorsal telencephalon and ventral spinal cord. In contrast, misexpression of Ngn2 inMash1-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 Ngn2functions 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 ofMash1 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.

Keywords

Footnotes

  • 3 Present address: Genes & Development Research Group, Health Sciences Center, University of Calgary, Foothills Hospital, Calgary, Alberta, T2N 4N1 Canada.

  • 4 These authors contributed equally to this work.

  • 5 Corresponding author.

  • E-MAIL francois{at}igbmc.u-strasbg.fr; FAX 33-388-65-32-01.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.940902.

    • Received August 27, 2001.
    • Accepted December 11, 2001.
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