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Abstract

The development of the vertebrate head is a complex process, in which the neural crest and the ectomesenchyme in particular plays a leading role. Craniofacial abnormalities are relatively common in humans and their pathogenesis often involves defects in the development and differentiation of neural crest
cells and its derivatives. Despite the importance of the ectomesenchyme, not much is known about the molecular basis of its differentiation and the developmental trajectories that form the cell types that shape the adult face. Here we use scRNA-seq technology to analyze the development of the ectomesenchyme of
the mouse frontonasal prominence from E10.5 through to E14.5 at a transcriptomic level. Our results reveal a remarkable complexity and heterogeneity of the ectomesenchyme, which clustered into 13 cell populations with distinct
transcriptomes, a number of which were entirely novel. Higher resolution clustering of these
populations revealed additional heterogeneity. Finally, RNA velocity analysis recapitulated developmental trajectories and revealed that the ectomesenchyme already committed to these cell populations at a surprisingly early stage (E10.5, E11.5).