Sonic Hedgehog Regulates Integrin Activity, Cadherin Contacts, and Cell Polarity to Orchestrate Neural Tube Morphogenesis

Abstract

In vertebrates, the embryonic nervous system is shaped and patterned by a series of temporally and spatially regulated cell divisions, cell specifications, and cell adhesions and movements. Morphogens of the Hedgehog, Wnt, and bone morphogenetic protein families have been shown to play a crucial role in the control of cell division and specification in the trunk neural tube, but their possible implication in the regulation of adhesive events has been poorly documented. In the present study, we demonstrate that Sonic hedgehog regulates neural epithelial cell adhesion and polarity through regulation of integrin activity, cadherin cell-cell contact, and cell polarity genes in immature neural epithelial cells before the specification of neuronal cells. We propose that Sonic hedgehog orchestrates neural tube morphogenesis by coordinating adhesive and motility events with cell proliferation and differentiation.