Single-cell transcriptome profiling reveals developmental trajectory and transcriptional regulatory networks of mouse maxillary prominence

During embryonic development of vertebrates, neural crest- derived mesenchymal cells within the maxillary prominences undergo precisely coordinated proliferation and differentiation to give rise to a series of craniofacial structures, such as tooth and secondary palate. However, the transcriptional regulatory networks underpinning such an intricate process have not been fully elucidated. Here we combined bulk and single-cell RNA-Seq to comprehensively characterize the transcriptome dynamics during mouse maxillary development from embryonic day (E) 10.5 to 14.5. We identified mesenchymal cell populations that represent different developmental states and inferred their developmental trajectory, demonstrating that a cell fate divergence toward the palatal versus dental mesenchyme lineage occurs at E11.5. We further identified the core transcriptional regulators associated with maxillary cell fate transitions and deduced the gene regulatory networks directed by these factors. We further demonstrated that Foxp1 regulates genes involved in skeletal and cartilage development and is required for efficient osteogenesis. Collectively, our study provides rich resources and important insights for achieving a systems level understanding of craniofacial morphogenesis and abnormality. Single cell RNA-Seq of E10.5, E11.5, E12.5, E14.5 mouse embryonic maxillary prominence tissue.