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During late embryonic development in mice, myogenic progenitors migrate to discrete sites to form individual muscles. The detailed mechanism of this process remains unclear. Using mouse levator veli palatini (LVP) development as a model, we systematically investigated how a distinct connective tissue subpopulation, perimysial fibroblasts, communicates with myogenic cells to regulate mouse pharyngeal myogenesis. Using single-cell RNAseq data analysis, we identified that TGF-\u03b2 signaling is a key regulator for the perimysial fibroblasts. Loss of TGF-\u03b2 signaling in the neural crest-derived palatal mesenchyme leads to defects in perimysial fibroblasts and muscle malformation in the soft palate in\n                    <jats:italic>\n                      Osr2\n                      <jats:sup>Cre<\/jats:sup>\n                      ;Tgfbr1\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    mice. In particular, Creb5, a transcription factor expressed in the perimysial fibroblasts, cooperates with TGF-\u03b2 signaling to activate expression of\n                    <jats:italic>Fgf18<\/jats:italic>\n                    . Moreover, Fgf18 supports pharyngeal muscle development\n                    <jats:italic>in vivo<\/jats:italic>\n                    and exogenous Fgf18 can partially rescue myogenic cell numbers in\n                    <jats:italic>\n                      Osr2\n                      <jats:sup>Cre<\/jats:sup>\n                      ;Tgfbr1\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    samples, illustrating that TGF-\u03b2-regulated Fgf18 signaling is required for LVP development. Collectively, our findings reveal the mechanism by which TGF-\u03b2 signaling achieves its functional specificity in defining the perimysial-to-myogenic signals for pharyngeal myogenesis.\n                  <\/jats:p>","DOI":"10.7554\/elife.80405","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T03:15:13Z","timestamp":1670814913000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.80405","source":"Crossref","is-referenced-by-count":18,"title":["TGF-\u03b2 signaling and Creb5 cooperatively regulate Fgf18 to control pharyngeal muscle development"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9944-2604","authenticated-orcid":true,"given":"Jifan","family":"Feng","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Craniofacial Molecular Biology, University of Southern California","place":["Los Angeles, United 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