title: ALK5-mediated transforming growth factor β signaling in neural crest cells controls craniofacial muscle development via tissue-tissue interactions.
abstract: The development of the craniofacial muscles requires reciprocal interactions with surrounding craniofacial tissues that originate from cranial neural crest cells (CNCCs). However, the molecular mechanism involved in the tissue-tissue interactions between CNCCs and muscle progenitors during craniofacial muscle development is largely unknown. In the current study, we address how CNCCs regulate the development of the tongue and other craniofacial muscles using Wnt1-Cre; Alk5(fl/fl) mice, in which loss of Alk5 in CNCCs results in severely disrupted muscle formation. We found that Bmp4 is responsible for reduced proliferation of the myogenic progenitor cells in Wnt1-Cre; Alk5(fl/fl) mice during early myogenesis. In addition, Fgf4 and Fgf6 ligands were reduced in Wnt1-Cre; Alk5(fl/fl) mice and are critical for differentiation of the myogenic cells. Addition of Bmp4 or Fgf ligands rescues the proliferation and differentiation defects in the craniofacial muscles of Alk5 mutant mice in vitro. Taken together, our results indicate that CNCCs play critical roles in controlling craniofacial myogenic proliferation and differentiation through tissue-tissue interactions.
authors.affiliation: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, California, USA.
authors.forename: Arum
authors.initials: A
authors.lastname: Han
authors.affiliation: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, California, USA.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, California, USA.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Li
authors.affiliation: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, California, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Pelikan
authors.affiliation: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, California, USA ychai@usc.edu.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D055415:Bone Morphogenetic Protein 4 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D005152:Facial Muscles / Q000196:embryology*; D051519:Fibroblast Growth Factor 4 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D051522:Fibroblast Growth Factor 6 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008822:Mice, Transgenic; D024510:Muscle Development / Q000235:genetics*; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism*; D009924:Organ Culture Techniques; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D051898:Smad1 Protein / Q000378:metabolism; D051902:Smad5 Protein / Q000378:metabolism; D051904:Smad8 Protein / Q000378:metabolism; D014059:Tongue / Q000196:embryology; D014060:Tongue Diseases / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D051155:Wnt1 Protein / Q000235:genetics
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; C496446:Fgf4 protein, mouse; C486115:Fgf6 protein, mouse; D051519:Fibroblast Growth Factor 4; D051522:Fibroblast Growth Factor 6; D018125:Receptors, Transforming Growth Factor beta; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D051902:Smad5 Protein; C497798:Smad5 protein, mouse; D051904:Smad8 Protein; C491621:Smad9 protein, mouse; D016212:Transforming Growth Factor beta; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625842:Tgfbr1 protein, mouse