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Vol. 14, No. 1, pp. 67-80, January 1, 2000
1 Institut de Génétique et de Biologie
Moléculaire et Cellulaire, Centre National de la Recherche
Scientífique/Institut National de la Santé et
de la Recherche Médicale (IGBMC, CNRS/INSERM);
Université Louis Pasteur, BP163, Communauté Urbaine de
Strasbourg, France; 2 Howard Hughes Medical Institute,
Division of Biology 216-76, California Institute of Technology,
Pasadena, California 91125 USA
Neurogenin1 (Ngn1), Neurogenin2
(Ngn2), and Mash1 encode bHLH transcription factors
with neuronal determination functions. In the telencephalon, the
Ngns and Mash1 are expressed at high levels in
complementary dorsal and ventral domains, respectively. We found that
Ngn function is required to maintain these two separate expression domains, as Mash1 expression is up-regulated in the dorsal telencephalon of Ngn mutant embryos. We have taken
advantage of the replacement of the Ngns by Mash1 in
dorsal progenitors to address the role of the neural determination
genes in neuronal-type specification in the telencephalon. In
Ngn2 single and Ngn1; Ngn2 double mutants, a
population of early born cortical neurons lose expression of
dorsal-specific markers and ectopically express a subset of ventral
telencephalic-specific markers. Analysis of Mash1; Ngn2
double mutant embryos and of embryos carrying a Ngn2 to
Mash1 replacement mutation demonstrated that ectopic expression of Mash1 is required and sufficient to confer these ventral
characteristics to cortical neurons. Our results indicate that in
addition to acting as neuronal determinants, Mash1 and
Ngns play a role in the specification of dorsal-ventral
neuronal identity, directly linking pathways of neurogenesis and
regional patterning in the forebrain.
[Key Words: Cerebral cortex; thalamus; neurogenesis; mouse mutants; Mash1; neurogenin; bHLH gene]
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