TY - JOUR TI - An RNAi screen unravels the complexities of Rho GTPase networks in skin morphogenesis AU - Laurin, Melanie AU - Gomez, Nicholas C AU - Levorse, John AU - Sendoel, Ataman AU - Sribour, Megan AU - Fuchs, Elaine A2 - Parsons, Maddy A2 - Akhmanova, Anna VL - 8 PY - 2019 DA - 2019/09/25 SP - e50226 C1 - eLife 2019;8:e50226 DO - 10.7554/eLife.50226 UR - https://doi.org/10.7554/eLife.50226 AB - During mammalian embryogenesis, extensive cellular remodeling is needed for tissue morphogenesis. As effectors of cytoskeletal dynamics, Rho GTPases and their regulators are likely involved, but their daunting complexity has hindered progress in dissecting their functions. We overcome this hurdle by employing high throughput in utero RNAi-mediated screening to identify key Rho regulators of skin morphogenesis. Our screen unveiled hitherto unrecognized roles for Rho-mediated cytoskeletal remodeling events that impact hair follicle specification, differentiation, downgrowth and planar cell polarity. Coupling our top hit with gain/loss-of-function genetics, interactome proteomics and tissue imaging, we show that RHOU, an atypical Rho, governs the cytoskeletal-junction dynamics that establish columnar shape and planar cell polarity in epidermal progenitors. Conversely, RHOU downregulation is required to remodel to a conical cellular shape that enables hair bud invagination and downgrowth. Our findings underscore the power of coupling screens with proteomics to unravel the physiological significance of complex gene families. KW - stem cells KW - Rho GTPases KW - RNAi screen KW - morphogenesis KW - cell shape dynamics KW - planar cell polarity JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -