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 pr...

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Published in	Neuron (Cambridge, Mass.) Vol. 29; no. 2; pp. 401 - 413
Main Authors	Nieto, Marta, Schuurmans, Carol, Britz, Olivier, Guillemot, François
Format	Journal Article
Language	English
Published	United States Elsevier Inc 01.02.2001 Elsevier
Subjects	Animals Basic Helix-Loop-Helix Transcription Factors Cell Differentiation - genetics Cerebral Cortex - abnormalities Cerebral Cortex - embryology DNA-Binding Proteins - genetics DNA-Binding Proteins - physiology Genetics Lac Operon - physiology Life Sciences Mash1 gene Mice Mice, Mutant Strains Nerve Tissue Proteins - genetics Nerve Tissue Proteins - physiology neurogenin 2 Neurogenin2 gene Neuroglia - cytology Neuroglia - metabolism Neurons - cytology Neurons - metabolism Rats Rats, Wistar Stem Cells - metabolism Transcription Factors - genetics Transcription Factors - physiology
Online Access	Get full text
ISSN	0896-6273 1097-4199
DOI	10.1016/S0896-6273(01)00214-8

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Abstract	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.
AbstractList	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. 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. 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.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.
Author	Britz, Olivier Schuurmans, Carol Guillemot, François Nieto, Marta
Author_xml	– sequence: 1 givenname: Marta surname: Nieto fullname: Nieto, Marta – sequence: 2 givenname: Carol surname: Schuurmans fullname: Schuurmans, Carol – sequence: 3 givenname: Olivier surname: Britz fullname: Britz, Olivier – sequence: 4 givenname: François surname: Guillemot fullname: Guillemot, François email: francois@igbmc.u-strasbg.fr
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/11239431$$D View this record in MEDLINE/PubMed https://hal.science/hal-04110910$$DView record in HAL
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Snippet	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... 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...
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SubjectTerms	Animals Basic Helix-Loop-Helix Transcription Factors Cell Differentiation - genetics Cerebral Cortex - abnormalities Cerebral Cortex - embryology DNA-Binding Proteins - genetics DNA-Binding Proteins - physiology Genetics Lac Operon - physiology Life Sciences Mash1 gene Mice Mice, Mutant Strains Nerve Tissue Proteins - genetics Nerve Tissue Proteins - physiology neurogenin 2 Neurogenin2 gene Neuroglia - cytology Neuroglia - metabolism Neurons - cytology Neurons - metabolism Rats Rats, Wistar Stem Cells - metabolism Transcription Factors - genetics Transcription Factors - physiology
Title	Neural bHLH Genes Control the Neuronal versus Glial Fate Decision in Cortical Progenitors
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