Unbiased screening identifies TGF-beta signaling and Creb5 cooperatively regulate FGF18 to control pharyngeal muscle development

In the present work, we investigated the mechanism that regulates perimysial-to-myogenic communication using the development of the pharyngeal muscle LVP as a model. Using unbiased single-cell RNAseq (scRNAseq) data analysis combined with mouse genetic approaches, we identified TGF-beta signaling as the predominant signaling activity that enables the perimysial cells to interact with the adjacent myogenic cells during late pharyngeal muscle development. Furthermore, we identified that perimysial-specific regulator Creb5 interacts specifically with TGF-beta signaling to co-activate the expression of specific perimysial-to-myogenic signals such as Fgf18 to regulate pharyngeal myogenesis. Taken together, our findings reveal that TGF-b signaling and perimysial-specific regulators may cooperatively define perimysial-to-myogenic signals in regulating pharyngeal myogenesis. Single-cell transcriptomes were obtained from E14.5 control and Osr2-Cre;Alk5fl/fl soft palate tissue