title: FoxO6 affects Plxna4-mediated neuronal migration during mouse cortical development.
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 inFoxO6+/-andFoxO6-/-mice, showing migrating neurons halted in the intermediate zone. Using aFoxO6-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 ofFoxO6We then show that FoxO6 binds to DAF-16-binding elements in thePlexin A4(Plxna4) promoter region and affectsPlxna4expression. Finally, ectopicPlxna4expression restores radial migration inFoxO6+/-and siRNA-mediated knockdown models. In conclusion, the presented data provide insights into the molecular mechanisms whereby transcriptional programs drive cortical development.
authors: Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands.
authors: Ricardo H
authors: RH
authors: Paap
authors: Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands.
authors: Saskia
authors: S
authors: Oosterbroek
authors: Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands.
authors: Cindy M R J
authors: CMRJ
authors: Wagemans
authors: Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands.
authors: Lars
authors: L
authors: von Oerthel
authors: Brain Center Rudolf Magnus, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors: Raymond D
authors: RD
authors: Schellevis
authors: Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands.
authors: Annemarie J A
authors: AJA
authors: Vastenhouw-van der Linden
authors: Microarray Facility, Department of Molecular Cancer Research, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors: Marian J A
authors: MJA
authors: Groot Koerkamp
authors: Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands; m.f.m.hoekman@uva.nl m.p.smidt@uva.nl.
authors: Marco F M
authors: MFM
authors: Hoekman
authors: Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands; m.f.m.hoekman@uva.nl m.p.smidt@uva.nl.
authors: Marten P
authors: MP
authors: Smidt
keywords: FoxO6; Plxna4; cortex; development; radial migration