Prox1 regulates the subtype-specific development of caudal ganglionic eminence-derived GABAergic cortical interneurons

Goichi Miyoshi*, Allison Young, Timothy Petros, Theofanis Karayannis, Melissa McKenzie Chang, Alfonso Lavado, Tomohiko Iwano, Miho Nakajima, Hiroki Taniguchi, Z. Josh Huang, Nathaniel Heintz, Guillermo Oliver, Fumio Matsuzaki, Robert P. Machold, Gord Fishell

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Neurogliaform (RELN+) and bipolar (VIP+) GABAergic interneurons of the mammalian cerebral cortex provide critical inhibition locally within the superficial layers. While these subtypes are known to originate from the embryonic caudal ganglionic eminence (CGE), the specific genetic programs that direct their positioning, maturation, and integration into the cortical network have not been elucidated. Here, we report that in mice expression of the transcription factor Prox1 is selectively maintained in postmitotic CGE-derived cortical interneuron precursors and that loss of Prox1 impairs the integration of these cells into superficial layers. Moreover, Prox1 differentially regulates the postnatal maturation of each specific subtype originating from the CGE (RELN, Calb2/VIP, and VIP). Interestingly, Prox1 promotes the maturation of CGE-derived interneuron subtypes through intrinsic differentiation programs that operate in tandem with extrinsically driven neuronal activity-dependent pathways. Thus Prox1 represents the first identified transcription factor specifically required for the embryonic and postnatal acquisition of CGE-derived cortical interneuron properties.

Original languageEnglish (US)
Pages (from-to)12869-12889
Number of pages21
JournalJournal of Neuroscience
Volume35
Issue number37
DOIs
StatePublished - Sep 16 2015

Keywords

  • Bipolar
  • Mouse genetics
  • Neurogliaform
  • RELN
  • Transcription
  • VIP

ASJC Scopus subject areas

  • Neuroscience(all)

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