PI3K regulates intraepithelial cell positioning through Rho GTP-ases in the developing neural tube.

SUMMARY STATEMENTDuring neural tube development, PI3K pathway promotes cell survival and provides the apical-basal navigation clues that define the final location of neurons in the epithelium.\n\nSUMMARYPhosphatidylinositol 3-kinases (PI3Ks) are signal transducers of many biological processes. Class 1A PI3Ks are hetero dimers formed by a regulatory and a catalytic subunit. We have used the developing chicken neural tube (NT) to study the roles played by PI3K during the process of cell proliferation and differentiation. Notably, we have observed that in addition to its well characterized anti apoptotic activity, PI3K also plays a crucial role in intra epithelial cell positioning, and unlike its role in survival that mainly depends on AKT, the activity in cell positioning is mediated by Rho GTPase family members. Additionally, we have observed that activating mutations of PI3K that are remarkably frequent in many human cancers, cause an unrestrained basal migration of the neuroepithelial cells that end up breaking through the basal membrane invading the surrounding mesenchymal tissue. The mechanism described in this work contribute not only to acquire a greater knowledge of the intraepithelial cell positioning process, but also give new clues on how activating mutations of PI3K contribute to cell invasion during the first stages of tumour dissemination.