Neural bHLH genes control the neuronal versus glial fate decision in cortical progenitors.
We have addressed the role of the proneural bHLH genes Neurogenin2 (Ngn2) and Mash1 in the selection of neuronal and glial fates by neural stem cells. We show that mice mutant for both genes present severe defects in development of the cerebral cortex, including a reduction of neurogenesis and a premature and excessive generation of astrocytic precursors. An analysis of wild-type and mutant cortical progenitors in culture showed that a large fraction of Ngn2; Mash1 double-mutant progenitors failed to adopt a neuronal fate, instead remaining pluripotent or entering an astrocytic differentiation pathway. Together, these results demonstrate that proneural genes are involved in lineage restriction of cortical progenitors, promoting the acquisition of the neuronal fate and inhibiting the astrocytic fate.
Institut de Génétique et de Biologie Moléculaire, et Cellulaire, CNRS, INSERM, Université, Louis Pasteur, Boite Postale 163, 67404 Illkirch Cédex, Communauté Urbaine de, Strasbourg, France
M
M
Nieto
C
C
Schuurmans
O
O
Britz
F
F
Guillemot
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000235:genetics; D002540:Cerebral Cortex / Q000002:abnormalities / Q000196:embryology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D007763:Lac Operon / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C499317:Ascl1 protein, mouse; C499318:Ascl1 protein, rat; C491183:NEUROG2 protein, human; C102938:Neurog2 protein, mouse