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

Parras, Carlos M. and Schuurmans, Carol and Scardigli, Raffaella and Kim, Jaesang and Anderson, David J. and Guillemot, François (2002) Divergent functions of the proneural genes Mash1 and Ngn2 in the specification of neuronal subtype identity. Genes and Development, 16 (3). pp. 324-338. ISSN 0890-9369. doi:10.1101/gad.940902. https://resolver.caltech.edu/CaltechAUTHORS:20150312-125037711

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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 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1101/gad.940902DOIArticle
http://genesdev.cshlp.org/content/16/3/324PublisherArticle
ORCID:
AuthorORCID
Anderson, David J.0000-0001-6175-3872
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.
Funders:
Funding AgencyGrant Number
Spanish Ramón Areces FoundationUNSPECIFIED
European Molecular Biology Organization (EMBO)UNSPECIFIED
Human Frontiers Science ProgramUNSPECIFIED
Medical Research Council of CanadaUNSPECIFIED
Italian Telethon FoundationUNSPECIFIED
European Community TRM ProgramUNSPECIFIED
European Community Research and Technological Development ProgramUNSPECIFIED
Association pour la Recherche sur le CancerUNSPECIFIED
Ministère de l’Enseignement et de la RechercheUNSPECIFIED
INSERMUNSPECIFIED
Centre National de la Recherche Scientifique (CNRS)UNSPECIFIED
Hôpital Universitaire de StrasbourgUNSPECIFIED
Subject Keywords:Knock-in mutations; bHLH factors; CNS; PNS; neuronal specification
Issue or Number:3
DOI:10.1101/gad.940902
Record Number:CaltechAUTHORS:20150312-125037711
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150312-125037711
Official Citation:Divergent functions of the proneural genes Mash1 and Ngn2 in the specification of neuronal subtype identity Carlos M. Parras, Carol Schuurmans, Raffaella Scardigli, Jaesang Kim, David J. Anderson, and François Guillemot Genes Dev. February 1, 2002 16: 324-338; doi:10.1101/gad.940902
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:55734
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:12 Mar 2015 21:46
Last Modified:10 Nov 2021 20:49

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