21-P020 The apical–basal polarity kinase aPKC functions as a nuclear determinant and regulates cell proliferation and fate during Xenopus neurogenesis

During neurogenesis in Xenopus, apico-basally polarized superficial and non-polar deep cells take-up differential fates – only deep cells become primary neurons while superficial cells stay as progenitors for later wave(s) of neurogenesis. The polarity of the superficial cells is defined by the antagonistic interactions between apically localized atypical protein kinase C (aPKC) and basolateral Lethal Giant Larvae (Lgl). It is unknown whether the proteins affecting polarity of cells also affect their fate, and if so, then how membrane polarity information is transmitted to the nucleus is also not known. We show that over-expression of a constitutively active, membrane-tethered form of aPKC (aPKC-CAAX) suppresses primary neurogenesis, and promotes cell proliferation and superficial fate. Unexpectedly, these effects can be accounted for by a nuclear fraction of aPKC-CAAX, pointing towards shuttling of aPKC from membrane to the nucleus. Conversely, antagonising apical aPKC by Lgl2 over-expression causes depolarization and internalization of superficial cells; these internalized superficial cells form ectopic neurons when supplemented with a proneural factor like X-ngnr-1. These findings suggest that aPKC itself is a nuclear determinant, affecting mainly cell proliferation; and in the right environment, loss of aPKC is also permissive for a change in cell fate.