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FoxO6 affects Plxna4-mediated neuronal migration during mouse cortical development.

Ricardo H Paap1, Saskia Oosterbroek1, Cindy M R J Wagemans1

  • 1Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands.

Proceedings of the National Academy of Sciences of the United States of America
|October 30, 2016
PubMed
Summary

The transcription factor FoxO6 is crucial for proper neuronal migration during neocortical development. Its absence disrupts migration, impacting genes involved in cell adhesion and axon guidance.

Keywords:
FoxO6Plxna4cortexdevelopmentradial migration

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Molecular Biology

Background:

  • The forkhead transcription factor FoxO6 is highly expressed during murine neocortical development.
  • Its specific role in cortical development remains largely uncharacterized.

Purpose of the Study:

  • To investigate the function of FoxO6 in neocortical development.
  • To elucidate the molecular mechanisms underlying FoxO6's role in neuronal migration.

Main Methods:

  • Analysis of FoxO6 heterozygous (+/-) and knockout (--) mice.
  • siRNA-mediated knockdown of FoxO6 in the developing neocortex.
  • Genome-wide transcriptome analysis.
  • Chromatin immunoprecipitation and reporter assays to assess gene regulation.
  • Ectopic gene expression studies.

Main Results:

  • FoxO6 deficiency in mice leads to impaired radial neuronal migration, with neurons arrested in the intermediate zone.
  • FoxO6 is essential for correct radial migration in the developing neocortex.
  • Silencing FoxO6 alters the expression of genes critical for cell adhesion, axon guidance, and gliogenesis.
  • FoxO6 directly binds to the promoter of Plexin A4 (Plxna4) and regulates its expression.
  • Restoring Plxna4 expression rescues radial migration defects in FoxO6-deficient models.

Conclusions:

  • FoxO6 plays a vital role in regulating transcriptional programs that drive neocortical development.
  • The findings reveal a novel mechanism involving FoxO6 and Plxna4 in controlling neuronal migration.
  • This study provides molecular insights into the intricate processes governing brain development.