Journal
NATURE NEUROSCIENCE
Volume 12, Issue 10, Pages 1238-U51Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.2387
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Funding
- US National Institutes of Health [NS49553, NS45523, NS41590, F31 NS060421]
- Travis Roy Foundation
- Spastic Paraplegia Foundation
- Massachusetts Spinal Cord Injury research program
- Harvard Stem Cell Institute
- Swiss National Science Foundation
- Holcim Foundation
- National Science Foundation Graduate Research Fellowship
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The neuronal diversity of the CNS emerges largely from controlled spatial and temporal segregation of cell type-specific molecular regulators. We found that the transcription factor SOX6 controls the molecular segregation of dorsal (pallial) from ventral (subpallial) telencephalic progenitors and the differentiation of cortical interneurons, regulating forebrain progenitor and interneuron heterogeneity. During corticogenesis in mice, SOX6 and SOX5 were largely mutually exclusively expressed in pallial and subpallial progenitors, respectively, and remained mutually exclusive in a reverse pattern in postmitotic neuronal progeny. Loss of SOX6 from pallial progenitors caused their inappropriate expression of normally subpallium-restricted developmental controls, conferring mixed dorsal-ventral identity. In postmitotic cortical interneurons, loss of SOX6 disrupted the differentiation and diversity of cortical interneuron subtypes, analogous to SOX5 control over cortical projection neuron development. These data indicate that SOX6 is a central regulator of both progenitor and cortical interneuron diversity during neocortical development.
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