03-P115 Actin organisation and spatiotemporal control of endocytosis during cell–cell intercalation

The ventricular zone (VZ) of the embryonic dorsal telencephalon is a major site for generating cortical projection neurons. The transcription factor Pax6 is expressed in apical progenitors (APs) residing in the VZ in a rostrolateral-high to caudomediallow gradient and its levels are highest at early stages of corticogenesis. Previous studies mainly focused on Pax6 / mice have implicated Pax6 in cortical progenitor proliferation, migration, neuronal differentiation and formation of superficial cortical layers. We wish to explore the developmental significance of Pax6 expression levels in cortical progenitors at different developmental stages and levels across the rostral-caudal axis of the cortex. In order to address this issue, we are using a floxed Pax6 allele, where the exposure to Cre recombinase results in excision of Pax6 and initiation of YFP expression. Use of a tamoxifen-inducible Emx1-CreER driver allows us to remove the gene from cortical progenitors in a mosaic manner at times coincident with deepor superficial layer neurons being generated. Our preliminary results suggest that when Pax6 is removed from cortical progenitors at mid-stages of corticogenesis, the thickness of the postnatal cortex is severely reduced due to a remarkable under-production of superficial layer neurons. Deletion of Pax6 at late stages of corticogenesis results in the contribution of late-born Pax6 null cells to deeper laminar positions compared to Pax6 cells. This suggests that the normal low expression levels of Pax6 in late APs might have an effect on the specification of superficial layer neurons.