The diverse roles of FoxO6 in the developing and adult mouse brain

FoxO proteins are known to be involved in a wide array of biological processes, including apoptosis, cellular survival, differentiation and stress resistance. Recently, it came to the attention that FoxO6 displays a specific temporal and spatial expression pattern in the brain, implying that FoxO6 plays a role in the central nervous system. In this thesis the aim was to characterize the function of FoxO6 in the developing and adult mouse brain. Using different FoxO6 deficient animal models, we show that embryonic cortical cells are unable to migrate properly to the superficial layers of the cortex during cortical development. We also identified multiple target genes of FoxO6 and show that ectopic expression of one identified factor, Plxna4, was able to restore the hampered migration. Furthermore, we analyzed the effects of FoxO6 deficiency in the postnatal brain which showed phenotypical changes that resemble pathological changes observed in Cortical Malformation Syndromes, suggesting an involvement of FoxO6 in the development of cortical malformations. Next to these changes in cortical migration we observed other changes indicating that FoxO6 has multiple roles in the developing and adult brain. These overall changes are (more) complex and might even be related to each other. In summary, the research performed in this thesis contributes to the general knowledge of the developing cortex and provides novel insights in the role of FoxO6 and its downstream targets in multiple processes related to brain development and functioning.