Abstract:
:Cortical GABAergic interneurons have essential roles for information processing and their dysfunction is implicated in neuropsychiatric disorders. Transcriptional codes are elucidating mechanisms of interneuron specification in the MGE (a subcortical progenitor zone), which regulate their migration, integration, and function within cortical circuitry. Lhx6, a LIM-homeodomain transcription factor, is essential for specification of MGE-derived somatostatin and parvalbumin interneurons. Here, we demonstrate that some Lhx6⁻/⁻ MGE cells acquire a CGE-like fate. Using an in vivo MGE complementation/transplantation assay, we show that Lhx6-regulated genes Arx and CXCR7 rescue divergent aspects of Lhx6⁻/⁻ cell-fate and laminar mutant phenotypes and provide insight into a neonatal role for CXCR7 in MGE-derived interneuron lamination. Finally, Lhx6 directly binds in vivo to an Arx enhancer and to an intronic CXCR7 enhancer that remains active in mature interneurons. These data define the molecular identity of Lhx6 mutants and introduce technologies to test mechanisms in GABAergic interneuron differentiation.
journal_name
Neuronjournal_title
Neuronauthors
Vogt D,Hunt RF,Mandal S,Sandberg M,Silberberg SN,Nagasawa T,Yang Z,Baraban SC,Rubenstein JLdoi
10.1016/j.neuron.2014.02.030subject
Has Abstractpub_date
2014-04-16 00:00:00pages
350-64issue
2eissn
0896-6273issn
1097-4199pii
S0896-6273(14)00161-5journal_volume
82pub_type
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