Bhojwani, A. | Search bioRxiv

bioRxiv2024

FGF Signaling Regulates Development of the Anterior Fontanelle

The calvarial bones of the infant skull are connected by transient fibrous joints known as sutures and fontanelles, which are essential for reshaping during birth and postnatal growth. Genetic disorders such as Apert, Pfeiffer, Crouzon, and Bent bone dysplasia linked to FGFR2 variants often exhibit multi-suture craniosynostosis and a persistently open anterior fontanelle (AF). This study leverages mouse genetics and single-cell transcriptomics to determine how Fgfr2 regulates closure of the AF closure and its transformation into the frontal suture during postnatal development. We find that cells of the AF, marked by the tendon/ligament factor SCX, are spatially restricted to ecto- or endocranial domains and undergo regionally selective differentiation into ligament, bone, and cartilage. Differentiation of SCX+ AF cells is dependent on FGFR2 signaling in cells of the osteogenic fronts which, when fueled by FGF18 from the ectocranial mesenchyme, express the secreted WNT inhibitor WIF1 to regulate WNT signaling in neighboring AF cells. Upon loss of Fgfr2, Wif1 expression is lost, and cells of the AF retain a connective tissue-like fate failing to form the posterior frontal suture. This study provides new insights into regional differences in suture development by identifying an FGF-WNT signaling circuit within the AF that links frontal bone advancement with suture joint formation.

developmental biology↗

bioRxiv2022

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

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.

developmental biology↗