title: Novel tool to suppress cell proliferation in vivo demonstrates that myocardial and coronary vascular growth represent distinct developmental programs.
abstract: Cell proliferation, differentiation, and vascular growth are coordinated processes that are essential for embryonic development, tissue repair, and disease pathogenesis. Of interest, whether these critical processes are dependent upon each other has not been thoroughly explored. We have generated mice that conditionally express the cell cycle inhibitor p27(Kip1), following Cre-mediated recombination, as a tool to separate tissue proliferation from other cellular processes. Using the embryonic heart as a model, we show that myocardial proliferation and coronary development are genetically separable processes. Forced expression of p27, in both a wild-type and in a genetically sensitized background, resulted in ventricular hypoplasia without having any substantial effects on coronary development. We further demonstrate that Hedgehog signaling, which is essential for coronary vascular growth, does not control myocardial proliferation. Together, these studies strongly suggest that myocardial cell proliferation and coronary development are genetically separable programs exemplifying one of the many potential uses of this genetic tool.
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Kory J
authors.initials: KJ
authors.lastname: Lavine
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Schmid
authors.forename: Craig S
authors.initials: CS
authors.lastname: Smith
authors.forename: David M
authors.initials: DM
authors.lastname: Ornitz
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D003331:Coronary Vessels / Q000196:embryology* / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006321:Heart / Q000196:embryology*; D053823:Hedgehog Proteins / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology; D009924:Organ Culture Techniques; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D053823:Hedgehog Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005346:Fibroblast Growth Factors; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1