SOX6 controls dorsal progenitor identity and interneuron diversity during neocortical development.
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.
Azim
Eiman
E
Massachusetts General Hospital-Harvard Medical School Center for Nervous System Repair, Harvard Medical School, Boston, Massachusetts, USA.
Jabaudon
Denis
D
Fame
Ryann M
RM
Macklis
Jeffrey D
JD
D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency; D019521:Body Patterning; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation; D002465:Cell Movement; D018274:Electroporation / Q000379:methods; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D007395:Interneurons / Q000145:classification / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019579:Neocortex / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism; D055495:Neurogenesis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D055755:SOXD Transcription Factors / Q000172:deficiency / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D005968:Glutamate Decarboxylase; D049452:Green Fluorescent Proteins; D009419:Nerve Tissue Proteins; D018809:Proliferating Cell Nuclear Antigen; D055755:SOXD Transcription Factors; C102938:Neurog2 protein, mouse; C089186:Sox5 protein, mouse; C095939:Sox6 protein, mouse; C486336:Neurog1 protein, mouse; C402565:glutamate decarboxylase 1