ALK5-Mediated Transforming Growth Factor β Signaling in Neural Crest Cells Controls Craniofacial Muscle Development via Tissue-Tissue Interactions

• Published in: Molecular and cellular biology 2014-08, Vol.34 (16), p.3120-3131
• Main Authors: Han, Arum, Zhao, Hu, Li, Jingyuan, Pelikan, Richard, Chai, Yang
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - genetics; Bone Morphogenetic Protein 4 - biosynthesis; Bone Morphogenetic Protein 4 - genetics; Bone Morphogenetic Protein 4 - metabolism; Cell Differentiation - genetics; Cell Proliferation; Cells, Cultured; Facial Muscles - embryology; Fibroblast Growth Factor 4 - biosynthesis; Fibroblast Growth Factor 4 - genetics; Fibroblast Growth Factor 4 - metabolism; Fibroblast Growth Factor 6 - biosynthesis; Fibroblast Growth Factor 6 - genetics; Fibroblast Growth Factor 6 - metabolism; Gene Expression Regulation, Developmental; Mice; Mice, Transgenic; Muscle Development - genetics; Neural Crest - cytology; Neural Crest - metabolism; Organ Culture Techniques; Protein-Serine-Threonine Kinases - genetics; Receptor, Transforming Growth Factor-beta Type I; Receptors, Transforming Growth Factor beta - genetics; Signal Transduction - genetics; Smad1 Protein - metabolism; Smad5 Protein - metabolism; Smad8 Protein - metabolism; Tongue - embryology; Tongue Diseases - genetics; Transforming Growth Factor beta - genetics; Wnt1 Protein - genetics
• ISSN: 1098-5549; 0270-7306; 1098-5549
• DOI: 10.1128/MCB.00623-14

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.