| First Author | Li A | Year | 2016 |
| Journal | BMC Biol | Volume | 14 |
| Pages | 19 | PubMed ID | 26984772 |
| Mgi Jnum | J:250062 | Mgi Id | MGI:6102214 |
| Doi | 10.1186/s12915-016-0242-9 | Citation | Li A, et al. (2016) Mesodermal ALK5 controls lung myofibroblast versus lipofibroblast cell fate. BMC Biol 14:19 |
| abstractText | BACKGROUND: Epithelial-mesenchymal cross talk is centerpiece in the development of many branched organs, including the lungs. The embryonic lung mesoderm provides instructional information not only for lung architectural development, but also for patterning, commitment and differentiation of its many highly specialized cell types. The mesoderm also serves as a reservoir of progenitors for generation of differentiated mesenchymal cell types that include alphaSMA-expressing fibroblasts, lipofibroblasts, endothelial cells and others. Transforming Growth Factor beta (TGFbeta) is a key signaling pathway in epithelial-mesenchymal cross talk. Using a cre-loxP approach we have elucidated the role of the TGFbeta type I receptor tyrosine kinase, ALK5, in epithelial-mesenchymal cross talk during lung morphogenesis. RESULTS: Targeted early inactivation of Alk5 in mesodermal progenitors caused abnormal development and maturation of the lung that included reduced physical size of the sub-mesothelial mesoderm, an established source of specific mesodermal progenitors. Abrogation of mesodermal ALK5-mediated signaling also inhibited differentiation of cell populations in the epithelial and endothelial lineages. Importantly, Alk5 mutant lungs contained a reduced number of alphaSMA(pos) cells and correspondingly increased lipofibroblasts. Elucidation of the underlying mechanisms revealed that through direct and indirect modulation of target signaling pathways and transcription factors, including PDGFRalpha, PPARgamma, PRRX1, and ZFP423, ALK5-mediated TGFbeta controls a process that regulates the commitment and differentiation of alphaSMA(pos) versus lipofibroblast cell populations during lung development. CONCLUSION: ALK5-mediated TGFbeta signaling controls an early pathway that regulates the commitment and differentiation of alphaSMA(pos) versus LIF cell lineages during lung development. |
