dILA neurons in the dorsal spinal cord are the product of terminal and non-terminal asymmetric progenitor cell divisions, and require Mash1 for their development.
dILA and dILB neurons comprise the major neuronal subtypes generated in the dorsal spinal cord, and arise in a salt-and-pepper pattern from a broad progenitor domain that expresses the bHLH factor Mash1. In this domain, Mash1-positive and Mash1-negative cells intermingle. Using a Mash1(GFP) allele in mice, we show here that Mash1+ progenitors give rise to dILA and dILB neurons. Using retroviral tracing in the chick, we demonstrate that a single progenitor can give rise to a dILA and a dILB neuron, and that dILA neurons are the product of asymmetric progenitor cell divisions. In Mash1-null mutant mice, the development of dILA, but not of dILB neurons is impaired. We provide evidence that a dual function of Mash1 in neuronal differentiation and specification accounts for the observed changes in the mutant mice. Our data allow us to assign to Mash1 a function in asymmetric cell divisions, and indicate that the factor coordinates cell cycle exit and specification in the one daughter that gives rise to a dILA neuron.
Wildner
Hendrik
H
Max-Delbrück-Centrum for Molecular Medicine, Berlin-Buch, Germany.
Müller
Thomas
T
Cho
Seo-Hee
SH
Bröhl
Dominique
D
Cepko
Constance L
CL
Guillemot
Francois
F
Birchmeier
Carmen
C
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D014157:Transcription Factors; C499317:Ascl1 protein, mouse; C062602:transcription factor PTF1