A TGFβ-Smad4-Fgf6 signaling cascade controls myogenic differentiation and myoblast fusion during tongue development
| Autor: | Hu Zhao, Pablo Bringas, Joseph G. Hacia, Yang Chai, Carolina Parada, Dong Han |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
animal structures Fibroblast Growth Factor 6 Cellular differentiation Blotting Western Biology Muscle Development Real-Time Polymerase Chain Reaction Myoblasts Tendons Mice Myoblast fusion Cranial neural crest Tongue Transforming Growth Factor beta Internal medicine medicine Animals Myocyte Molecular Biology Cells Cultured In Situ Hybridization Research Articles Smad4 Protein Myogenesis Gene Expression Regulation Developmental Cell Differentiation Tendon formation Flow Cytometry beta-Galactosidase Tongue morphogenesis Mice Mutant Strains Cell biology medicine.anatomical_structure Endocrinology Neural Crest embryonic structures Microscopy Electron Scanning Signal Transduction Developmental Biology |
| Zdroj: | Development. 139:1640-1650 |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.076653 |
| Popis: | The tongue is a muscular organ and plays a crucial role in speech, deglutition and taste. Despite the important physiological functions of the tongue, little is known about the regulatory mechanisms of tongue muscle development. TGFβ family members play important roles in regulating myogenesis, but the functional significance of Smad-dependent TGFβ signaling in regulating tongue skeletal muscle development remains unclear. In this study, we have investigated Smad4-mediated TGFβ signaling in the development of occipital somite-derived myogenic progenitors during tongue morphogenesis through tissue-specific inactivation of Smad4 (using Myf5-Cre;Smad4flox/flox mice). During the initiation of tongue development, cranial neural crest (CNC) cells occupy the tongue buds before myogenic progenitors migrate into the tongue primordium, suggesting that CNC cells play an instructive role in guiding tongue muscle development. Moreover, ablation of Smad4 results in defects in myogenic terminal differentiation and myoblast fusion. Despite compromised muscle differentiation, tendon formation appears unaffected in the tongue of Myf5-Cre;Smad4flox/flox mice, suggesting that the differentiation and maintenance of CNC-derived tendon cells are independent of Smad4-mediated signaling in myogenic cells in the tongue. Furthermore, loss of Smad4 results in a significant reduction in expression of several members of the FGF family, including Fgf6 and Fgfr4. Exogenous Fgf6 partially rescues the tongue myoblast fusion defect of Myf5-Cre;Smad4flox/flox mice. Taken together, our study demonstrates that a TGFβ-Smad4-Fgf6 signaling cascade plays a crucial role in myogenic cell fate determination and lineage progression during tongue myogenesis. |
| Databáze: | OpenAIRE |
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