Mechanism of G protein–mediated regulation of apical cell constriction during neurulation by the non-GPCR protein DAPLE. (A) Expression of DAPLE is specifically induced during neurulation. Upon expression, DAPLE localizes to apical cell junctions of neuroepithelial cells, where it triggers G protein activation that leads to apical cell constriction and the subsequent bending of the neural plate. (B) Theme and variations of G protein–regulated apical cell constriction during epithelial tissue morphogenesis in vertebrates versus invertebrates. Heterotrimeric G proteins are part of a conserved ubiquitous machinery that controls actomyosin contractility, but they are regulated differently across species. In vertebrates, DAPLE fulfills the role performed by GPCRs in invertebrates as tissue-specific activators of signaling that drives apical cell constriction. (C) The G protein regulatory function of DAPLE (i.e., its GBA motif) was acquired during evolution in the transition from invertebrates to vertebrates, suggesting that the unconventional mechanism of G protein activation described here is an evolutionary innovation for epithelial remodeling in vertebrates.