title: BMP2 rescues deficient cell migration in Tgfbr3(-/-) epicardial cells and requires Src kinase.
abstract: During embryogenesis, the epicardium undergoes proliferation, migration, and differentiation into several cardiac cell types which contribute to the coronary vessels. The type III transforming growth factor-β receptor (TGFβR3) is required for epicardial cell invasion and development of coronary vasculature in vivo. Bone Morphogenic Protein-2 (BMP2) is a driver of epicardial cell migration. Utilizing a primary epicardial cell line derived from Tgfbr3(+/+) and Tgfbr3(-/-) mouse embryos, we show that Tgfbr3(-/-) epicardial cells are deficient in BMP2 mRNA expression. Tgfbr3(-/-) epicardial cells are deficient in 2-dimensional migration relative to Tgfbr3(+/+) cells; BMP2 induces cellular migration to Tgfbr3(+/+) levels without affecting proliferation. We further demonstrate that Src kinase activity is required for BMP2 driven Tgfbr3(-/-) migration. BMP2 also requires Src for filamentous actin polymerization in Tgfbr3(-/-) epicardial cells. Taken together, our data identifies a novel pathway in epicardial cell migration required for development of the coronary vessels.
authors.affiliation: a Department of Pharmacology and Toxicology , University of Arizona , Tucson , AZ , USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Allison
authors.affiliation: a Department of Pharmacology and Toxicology , University of Arizona , Tucson , AZ , USA.
authors.forename: Daniella
authors.initials: D
authors.lastname: Espiritu
authors.affiliation: a Department of Pharmacology and Toxicology , University of Arizona , Tucson , AZ , USA.|b Southwest Environmental Health Sciences Center, University of Arizona , Tucson , AZ , USA.|c Steele Children's Research Center, University of Arizona , Tucson , AZ , USA.|d Sarver Heart Center, University of Arizona , Tucson , AZ , USA.|e Bio5 Institute, University of Arizona , Tucson , AZ , USA.
authors.forename: Todd D
authors.initials: TD
authors.lastname: Camenisch
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D010496:Pericardium / Q000166:cytology*; D058105:Polymerization; D011509:Proteoglycans / Q000172:deficiency* / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000172:deficiency* / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000199:Actins; D055396:Bone Morphogenetic Protein 2; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; C071736:betaglycan; D019061:src-Family Kinases
keywords: BMP2; Src; TGFβR3; epicardium; migration