Rho GTPases in endoderm development and differentiation

The embryonic foregut of the mouse embryo is lined by a layer of endoderm cells whose architecture changes during development. The transition from a squamous to columnar epithelial morphology is accompanied by the upregulation of an atypical Rho GTPase, Rhou. Subsequently, multi-layering of the epithelium at the site of organ bud formation is associated with the downregulation of Rhou. Rho-related small GTPases are known to play multiple roles in establishing and maintaining epithelial polarity, cytoskeletal organization, morphogenesis and differentiation of epithelial tissues, but their role in the early development of the endoderm in mammals is largely unexplored. Our recent study has shown that Rhou is required for maintaining F-actin polarization, epithelial morphogenesis and differentiation of the endoderm. Rhou expression responds to canonical WNT signaling and its activity influences the cytoskeletal organization and differentiation of endodermal cells, possibly via activation of JNK-mediated pathways. In this context, Rhou provides a possible link between β-catenin dependent WNT signaling and cellular processes normally associated with WNT/PCP pathways.