FoxO6 Affects Plxna4-mediated Neuronal Migration During Mouse Cortical Development

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2016 Oct 30

PMID 27791111

Citations 12

Authors

Ricardo H Paap

Saskia Oosterbroek

Cindy M R J Wagemans

Lars Von Oerthel

Raymond D Schellevis

Annemarie J A Vastenhouw-van der Linden

Marian J A Groot Koerkamp

Marco F M Hoekman

Marten P Smidt

Affiliations

Soon will be listed here.

Abstract

The forkhead transcription factor FoxO6 is prominently expressed during development of the murine neocortex. However, its function in cortical development is as yet unknown. We now demonstrate that cortical development is altered in and mice, showing migrating neurons halted in the intermediate zone. Using a -directed siRNA approach, we substantiate the requirement of FoxO6 for a correct radial migration in the developing neocortex. Subsequent genome-wide transcriptome analysis reveals altered expression of genes involved in cell adhesion, axon guidance, and gliogenesis upon silencing of We then show that FoxO6 binds to DAF-16-binding elements in the () promoter region and affects expression. Finally, ectopic expression restores radial migration in and siRNA-mediated knockdown models. In conclusion, the presented data provide insights into the molecular mechanisms whereby transcriptional programs drive cortical development.

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