WDR5 Stabilizes Actin Architecture to Promote Multiciliated Cell Formation

The actin cytoskeleton is critical to shape cells and pattern intracellular organelles, which collectively drives tissue morphogenesis. In multiciliated cells (MCCs), apical actin drives expansion of the cell surface necessary to host hundreds of cilia. The apical actin also forms a lattice to uniformly distribute basal bodies. 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 MCCs. Unexpectedly in MCCs, WDR5 has a function independent of chromatin modification. 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 lattice architecture. In summary, we identify a non-chromatin role for WDR5 in stabilizing F-actin in MCCs. [Display omitted] •WDR5 has a chromatin modification-independent role in multiciliated cell formation•The β-propeller structure of WDR5 is essential, but not sufficient, for ciliogenesis•WDR5 controls apical cell expansion and basal body patterning•WDR5 binds actin and γ-tubulin and stabilizes the actin network Kulkarni et al. uncover a chromatin modification-independent function for the H3K4 methyltransferase subunit WDR5 in multiciliated cell formation. WDR5 localizes to basal bodies at the ciliary base, where it stabilizes the actin lattice that allows multiciliated cells to expand their apical surface, pattern basal bodies, and generate hundreds of cilia.