WDR5 stabilizes actin architecture to promote multiciliated cell formation

HIGHLIGHTS WDR5 has an H3K4 independent role in the formation of multiciliated cells. WDR5 controls apical cell expansion, basal body patterning, and ciliogenesis in multiciliated cells. WDR5 localizes near the ciliary base where it connects basal bodies to F-actin. WDR5 stabilizes the apical actin network in multiciliated cells. SUMMARY The actin cytoskeleton is critical to shape cells and pattern intracellular organelles to drive tissue morphogenesis. In multiciliated cells (MCCs), apical actin forms a lattice that drives expansion of the cell surface necessary to host hundreds of cilia. The actin lattice also uniformly distributes basal bodies across this surface. This apical actin network is dynamically remodeled, but the molecules that regulate its architecture remain poorly understood. We identify the chromatin modifier, WDR5, as a regulator of apical F-actin in multiciliated cells. Unexpectedly, WDR5 functions independently of chromatin modification in MCCs. Instead, we discover a scaffolding role for WDR5 between the basal body and F-actin. Specifically, WDR5 binds to basal bodies and migrates apically, where F-actin organizes around WDR5. Using a monomer trap for G-actin, we show that WDR5 stabilizes F-actin to maintain apical lattice architecture. In summary, we identify a novel, non-chromatin role for WDR5 in stabilizing F-actin in multiciliated cells. IN BRIEF Kulkarni et al discover a chromatin independent function for WDR5 in multiciliated cell formation. WDR5 localizes to the base of cilia and functions as a scaffold between the basal bodies and the apical actin lattice. There, WDR5 stabilizes the actin lattice that allows multiciliated cells to expand their apical surface, pattern basal bodies, and generate hundreds of cilia.