FoxO6 affects Plxna4-mediated neuronal migration during mouse cortical development.
basic_science · Level V
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- Record sourced from PubMed, PMID 27791111.
- Also identified by DOI 10.1073/pnas.1609111113 and PMC identifier 5111667.
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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 <i>FoxO6</i><sup>+/-</sup> and <i>FoxO6</i><sup><i>-/-</i></sup> mice, showing migrating neurons halted in the intermediate zone. Using a <i>FoxO6</i>-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 <i>FoxO6</i> We then show that FoxO6 binds to DAF-16-binding elements in the <i>Plexin A4</i> (<i>Plxna4</i>) promoter region and affects <i>Plxna4</i> expression. Finally, ectopic <i>Plxna4</i> expression restores radial migration in <i>FoxO6</i><sup><i>+/-</i></sup> and siRNA-mediated knockdown models. In conclusion, the presented data provide insights into the molecular mechanisms whereby transcriptional programs drive cortical development.