During development, the lung mesoderm generates a variety of cell lineages, including airway and vascular smooth muscle. Epigenetic changes in adult lung mesodermal lineages are thought to contribute towards diseases such as idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease, although the factors that regulate early lung mesoderm development are unknown. We show in mouse that the PRC2 component Ezh2 is required to restrict smooth muscle differentiation in the developing lung mesothelium. Mesodermal loss of Ezh2 leads to the formation of ectopic smooth muscle in the submesothelial region of the developing lung mesoderm. Loss of Ezh2 specifically in the developing mesothelium reveals a mesothelial cell-autonomous role for Ezh2 in repression of the smooth muscle differentiation program. Loss of Ezh2 derepresses expression of myocardin and Tbx18, which are important regulators of smooth muscle differentiation from the mesothelium and related cell lineages. Together, these findings uncover an Ezh2-dependent mechanism to restrict the smooth muscle gene expression program in the developing mesothelium and allow appropriate cell fate decisions to occur in this multipotent mesoderm lineage.
The authors declare no competing or financial interests.
M.S. and E.E.M. designed the experiments, analyzed the data and wrote the paper. M.S. performed experiments. M.M.L., L.C. and S.Z. performed histological sectioning, in situ hybridization and IHC of sectioned tissue.
This work was supported by funding from the National Institutes of Health [HL087825, HL110942 and HL100405]. Deposited in PMC for release after 12 months.
Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.134932.supplemental
- Received January 7, 2016.
- Accepted August 17, 2016.