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Publication : Plasticity in airway smooth muscle differentiation during mouse lung development.

First Author  Goodwin K Year  2023
Journal  Dev Cell Volume  58
Issue  5 Pages  338-347.e4
PubMed ID  36868232 Mgi Jnum  J:340972
Mgi Id  MGI:7448307 Doi  10.1016/j.devcel.2023.02.002
Citation  Goodwin K, et al. (2023) Plasticity in airway smooth muscle differentiation during mouse lung development. Dev Cell 58(5):338-347.e4
abstractText  It has been proposed that smooth muscle differentiation may physically sculpt airway epithelial branches in mammalian lungs. Serum response factor (SRF) acts with its co-factor myocardin to activate the expression of contractile smooth muscle markers. In the adult, however, smooth muscle exhibits a variety of phenotypes beyond contractile, and these are independent of SRF/myocardin-induced transcription. To determine whether a similar phenotypic plasticity is exhibited during development, we deleted Srf from the mouse embryonic pulmonary mesenchyme. Srf-mutant lungs branch normally, and the mesenchyme displays mechanical properties indistinguishable from controls. scRNA-seq identified an Srf-null smooth muscle cluster, wrapping the airways of mutant lungs, which lacks contractile smooth muscle markers but retains many features of control smooth muscle. Srf-null embryonic airway smooth muscle exhibits a synthetic phenotype, compared with the contractile phenotype of mature wild-type airway smooth muscle. Our findings identify plasticity in embryonic airway smooth muscle and demonstrate that a synthetic smooth muscle layer promotes airway branching morphogenesis.
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