MACF1 Controls Migration and Positioning of Cortical GABAergic Interneurons in Mice

Minhan Ka, Jeffrey J. Moffat, Woo Yang Kim

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

GABAergic interneurons develop in the ganglionic eminence in the ventral telencephalon and tangentially migrate into the cortical plate during development. However, key molecules controlling interneuron migration remain poorly identified. Here, we show that microtubule-actin cross-linking factor 1 (MACF1) regulates GABAergic interneuron migration and positioning in the developing mouse brain. To investigate the role of MACF1 in developing interneurons, we conditionally deleted the MACF1 gene in mouse interneuron progenitors and their progeny using Dlx5/6-Cre-IRES-EGFP and Nkx2.1-Cre drivers. We found that MACF1 deletion results in a marked reduction and defective positioning of interneurons in the mouse cerebral cortex and hippocampus, suggesting abnormal interneuron migration. Indeed, the speed and mode of interneuron migration were abnormal in the MACF1-mutant brain, compared with controls. Additionally, MACF1-deleted interneurons showed a significant reduction in the length of their leading processes and dendrites in the mouse brain. Finally, loss of MACF1 decreased microtubule stability in cortical interneurons. Our findings suggest that MACF1 plays a critical role in cortical interneuron migration and positioning in the developing mouse brain.

Original languageEnglish (US)
Pages (from-to)5525-5538
Number of pages14
JournalCerebral cortex (New York, N.Y. : 1991)
Volume27
Issue number12
DOIs
StatePublished - Dec 1 2017

Fingerprint

Interneurons
Microtubules
Actins
Brain
Cerebral Cortex
Telencephalon
Dendrites
Hippocampus

Keywords

  • interneuron
  • leading process
  • MACF1
  • microtubule
  • migration

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

MACF1 Controls Migration and Positioning of Cortical GABAergic Interneurons in Mice. / Ka, Minhan; Moffat, Jeffrey J.; Kim, Woo Yang.

In: Cerebral cortex (New York, N.Y. : 1991), Vol. 27, No. 12, 01.12.2017, p. 5525-5538.

Research output: Contribution to journalArticle

Ka, Minhan ; Moffat, Jeffrey J. ; Kim, Woo Yang. / MACF1 Controls Migration and Positioning of Cortical GABAergic Interneurons in Mice. In: Cerebral cortex (New York, N.Y. : 1991). 2017 ; Vol. 27, No. 12. pp. 5525-5538.
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