Hedgehog Signaling Regulates Epithelial Morphogenesis to Position the Ventral Embryonic Midline

Despite much progress toward understanding how epithelial morphogenesis is shaped by intra-epithelial processes including contractility, polarity, and adhesion, much less is known regarding how such cellular processes are coordinated by extra-epithelial signaling. During embryogenesis, the coelomic epithelia on the two sides of the chick embryo undergo symmetrical lengthening and thinning, converging medially to generate and position the dorsal mesentery (DM) in the embryonic midline. We find that Hedgehog signaling, acting through downstream effectors Sec5 (ExoC2), an exocyst complex component, and RhoU (Wrch-1), a small GTPase, regulates coelomic epithelium morphogenesis to guide DM midline positioning. These effects are accompanied by changes in epithelial cell-cell alignment and N-cadherin and laminin distribution, suggesting Hedgehog regulation of cell organization within the coelomic epithelium. These results indicate a role for Hedgehog signaling in regulating epithelial morphology and provide an example of how transcellular signaling can modulate specific cellular processes to shape tissue morphogenesis. [Display omitted] •Convergence of the coelomic epithelium involves cell flattening and disorganization•Hh signaling regulates coelomic epithelium morphogenesis and N-cadherin distribution•Sec5 and RhoU function downstream of Hh•Hh signaling controls dorsal mesentery midline positioning The regulation of epithelial morphogenesis by external signaling is not well understood. Arraf et al. identify a Hedgehog-regulated molecular module that regulates convergence, flattening, and cell arrangement in the coelomic epithelium to guide placement of the dorsal mesentery in the embryonic midline.