Single-cell multiome characterizing intercellular communication and intracellular regulation of epithelium and mesenchymal during secondary palate development in mice

Cell-cell communication between adjacent tissues is fundamental to orchestrating organ morphogenesis. During secondary palate development, interactions between epithelial and mesenchymal cells regulate epithelial-mesenchymal signaling, thereby controlling cell proliferation, differentiation, and tissue patterning. However, the precise molecular mechanisms underlying these interactions remain largely unexplored. In this study, we employed single-cell multiome sequencing to simultaneously profile chromatin accessibility and gene expression in 35,150 individual cells isolated from the developing mouse secondary palate at embryonic days E12.5, E13.5, E14.0, and E14.5. Our analysis revealed that intercellular signaling plays a pivotal role in directing secondary palate morphogenesis, with WNT, BMP, and PDGF pathways emerging as key regulators of this process. These pathways exhibit peak activity at E12.5, followed by a progressive decline toward E14.5. Notably, WNT signaling is predominantly enriched in the nasal epithelium, mediating interactions with neighboring cell populations, while BMP signaling is more prominent in the oral epithelium. Additionally, PDGF signaling exhibits enhanced activity in the dental epithelium, indicating its role in coordinating epithelial-mesenchymal interactions during palatal development. Collectively, these findings provide novel insights into the spatiotemporal associations of WNT, BMP, and PDGF signaling with intercellular communication during secondary palate development, suggesting that these pathways may contribute to the cellular dynamics underlying secondary palate morphogenesis. Moreover, they underscore the need for further investigation.