YAP is essential for tissue tension to ensure vertebrate 3D body shape

Abstract

Graphical Abstract

Crumbling under Pressure

“…A screen for genes required for medaka fish development identified a mutant (hirami), which mapped to the YAP transcription factor locus (Porazinski et al, 2015). These YAP mutants had improperly shaped or flattened embryos, and interestingly, embryo collapse correlated with orientation relative to the gravitational pull of earth.…”

“…While much of our knowledge on YAP mechanosensitivity is from cell culture, an outstanding question is what cells or tissue types require YAP activity during embryogenesis and homeostasis? Interestingly, the authors note that YAP may function in a cell non-autonomous manner (Porazinski et al, 2015).…”

“…Here, they identified ARHGAP18, a RhoA-specific GTPase activating protein (GAP), as having reduced expression following YAP-knockdown (Porazinski et al, 2015). Rho GAPs bind to activated GTPases, catalyze the hydrolysis of GTP, and inactivate the GTPase.…”

“…It is surprising and counterintuitive that the loss of a RhoA GAP, ARHGAP18, would lead to decreased Myosin-II activation and potentially decreased tension (Porazinski et al, 2015). In many cases, a loss of a RhoA GAP increases active RhoA and actomyosin contraction (Miller and Bement, 2009), which is the opposite result observed in medaka YAP mutants.…”

“…Work in Drosophila imaginal disc development shows Moesin, an ERM protein that links the apical membrane to the cell cortex, recruits ARHGAP18 to the apical cortex of epithelial cells (Neisch et al, 2013). Overexpression of apically anchored ARHGAP18 can stimulate cell proliferation, an intriguing result considering YAP medaka mutants may have less proliferation and increased apoptosis (Porazinski et al, 2015). Drosophila ARHGAP18, through an unknown mechanism, also promoted Rac1 activation, which suggests cross-talk of the Rho and Rac pathways (Neisch et al, 2013).…”