Plasticity in airway smooth muscle differentiation during mouse lung development

Katharine Goodwin, Bezia Lemma, Pengfei Zhang, Adam Boukind, Celeste M. Nelson

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)338-347.e4
JournalDevelopmental cell
Volume58
Issue number5
DOIs
StatePublished - Mar 13 2023

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology
  • Molecular Biology
  • Cell Biology
  • Developmental Biology

Keywords

  • mechanobiology
  • morphodynamics
  • stiffness

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