ArhGEF18 regulated Rho signaling in vertebrate retina development

Epithelia consisting of highly polarized columnar cells contribute to many organs during development, including the central nervous system. Epithelial organization is essential for proliferation and differentiation of progenitor cells and subsequent organ morphology and function. Small GTPases of the Rho family are important regulators of cellular morphology and polarity. We recently identified ArhGEF18 as a key regulator of RhoA-Rock2 signaling that is crucial for maintenance of polarity in the vertebrate retinal epithelium. ArhGEF18 is required to maintain apico-basal polarity, localization of tight junctions and cortical actin, thus shaping cellular morphology. Loss of ArhGEF18 activity results in increased proliferation and reduced cell cycle exit. Together, these perturbations result in a severely misshaped embryonic eye, where the stereotype arrangement of retinal cell types is randomized. Our findings reveal an important role for RhoA-Rock2 signaling to maintain apico-basal polarity in retinal progenitor cells, which is essential for subsequent cellular differentiation, morphology and eventually organ function.