Understanding the development of oral epithelial organs through single cell transcriptomic analysis

Abstract

During vertebrate craniofacial development, the oral epithelium begins as a simple and morphologically homogeneous tissue. It then gives rise to locally complex structures, including the developing teeth, salivary glands, and taste buds. While there is significant knowledge about the molecular mechanisms regulating the morphogenesis of these organs at later stages, how the epithelium is initially patterned and specified to generate diverse cell types and organs remains largely unknown. To elucidate the genetic programs that direct the formation of distinct oral epithelial populations, we mapped the transcriptional landscape of embryonic day (E) 12 mouse mandibular epithelia at single cell resolution. Our analysis identified key transcription factors and gene regulatory networks that define different epithelial cell types as well as regions patterned along the oral-aboral axis. By examining the spatiotemporal expression of region-specific markers in embryonic mandibles, our results pointed to a model where the dental field is progressively confined to its position by the formation of the aboral epithelium anteriorly and the non-dental oral epithelium posteriorly. Using our data, we also identified Ntrk2 as a promoter of cell proliferation in the forming incisor, contributing to its invagination. Together, our results provide a detailed transcriptional atlas of the developing mandibular epithelium and unveil new genetic markers and regulators that are present during the specification of various oral epithelial structures.