The molecular anatomy of mammalian upper lip and primary palate fusion at single cell resolution

The mammalian lip/primary palate form when coordinated growth and morphogenesis bring the nasal and maxillary processes into contact, the epithelia co-mingle, remodel and clear from the fusion site to allow mesenchyme continuity. Although several genes required for fusion have been identified, an integrated molecular and cellular description of the overall process is lacking. Here we employ single cell RNA sequencing of the developing mouse face to identify ectodermal, mesenchymal, and endothelial populations associated with patterning and fusion of the facial prominences. This analysis indicated that key cell populations at the fusion site exist within the periderm, basal epithelial cells and adjacent mesenchyme. We describe the expression profiles that make each population unique, and the signals that potentially integrate their behaviour. Overall, these data provide a comprehensive high-resolution description of the various cell populations participating in fusion of the lip/primary palate as well as formation of the nasolacrimal groove, and they furnish a powerful resource for those investigating the molecular genetics of facial development and facial clefting that can be mined for critical mechanistic information concerning this prevalent human birth defect.