TGF-b signaling regulates craniofacial muscle development through a non-autonomous mechanism

Objectives: Skeletal muscles are formed from two cell lineages, myogenic and fibroblastic. Fibroblastic cells give rise to the supportive connective tissue of skeletal muscles such as tendon. It remains unknown how myogenic and fibroblastic cell-cell interaction may affect cell fate determination and organization of skeletal muscle. In the present study, we investigated the functional significance of cell-cell interaction in regulating skeletal muscle development.

Methods: 1) We investigated CNC cell fate map during skeletal muscle development in the craniofacial region. 2) We investigated the function of TGF-b signaling in the CNC cell lineage during skeletal muscle formation. 3) We performed primary cell culture of E12.5 tongue primordium.

Results: 1) We found that cranial neural crest (CNC) cells give rise to the fibroblastic cells of the tongue skeletal muscle in mice. 2) Loss of Tgfbr2 in CNC cells (Wnt1-Cre;Tgfbr2^flox/flox) results in microglossia, decreased myogenic cell proliferation, and reduced Scleraxis expression in the tongue. 3) Wnt1-Cre;Tgfbr2^flox/flox mice also had decreased Fgf10 expression, disorganization of tongue muscles, and reduced myofibril numbers in the tongue primordium. 4) The addition of FGF10 rescued the reduced myofibril number in Wnt1-Cre;Tgfbr2^flox/flox mice.

Conclusion: TGF-b signaling has a critical function in tongue skeletal muscle development, one that is required non-autonomously in the surrounding CNC cells. Supported by R01 DE012711 and R01 DE014078, NIDCR, NIH.