MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling

Minhan Ka, Eui Man Jung, Ulrich Mueller, Woo Yang Kim

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Neuronal migration and subsequent differentiation play critical roles for establishing functional neural circuitry in the developing brain. However, the molecular mechanisms that regulate these processes are poorly understood. Here, we show that microtubule actin crosslinking factor 1 (MACF1) determines neuronal positioning by regulating microtubule dynamics and mediating GSK-3 signaling during brain development. First, using MACF1 floxed allele mice and in utero gene manipulation, we find that MACF1 deletion suppresses migration of cortical pyramidal neurons and results in aberrant neuronal positioning in the developing brain. The cell autonomous deficit in migration is associated with abnormal dynamics of leading processes and centrosomes. Furthermore, microtubule stability is severely damaged in neurons lacking MACF1, resulting in abnormal microtubule dynamics. Finally, MACF1 interacts with and mediates GSK-3 signaling in developing neurons. Our findings establish a cellular mechanism underlying neuronal migration and provide insights into the regulation of cytoskeleton dynamics in developing neurons.

Original languageEnglish (US)
Pages (from-to)4-18
Number of pages15
JournalDevelopmental Biology
Volume395
Issue number1
DOIs
StatePublished - Nov 1 2014

Keywords

  • Cytoskeleton
  • GSK-3
  • MACF1
  • Microtubule
  • Neuronal migration

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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