title: VEGF regulates relative allocation of Isl1+cardiac progenitors to myocardial and endocardial lineages.
abstract: A fundamental issue in organogenesis is how dichotomous fate decisions are made securing proper allocation of multipotent progenitors to their respective descendants. Previous lineage tracing analyses showing Isl1+/VEGFR2+cardiac progenitors in the second heart field give rise to both endocardium and myocardium suggest VEGF plays a role in this fate decision, conceivably promoting an endocardial fate. Isl1+multipotent progenitors and lineage-committed descendants thereof were visualized and quantified within their transition zone in the outflow tract. Forced VEGF expression during the critical E8.5-E10.5 interval tilted the balance between myocardial- and endocardial-committed progenitors towards the latter, culminating in generation of surplus endocardium developing at the expense of a much thinner myocardium. Experiments ruled-out that surplus endocardium is due to VEGF-induced endocardial proliferation and that reduced myocardium is due to myocardial apoptosis. Inducing VEGF after most Isl1+progenitors have been exhausted had no effect on the normal endocardia/myocardial ratio but instead produced an unrelated coronary phenotype. Together, these results uncover a novel role for VEGF in controlling proper allocation of Isl1+cardiac progenitors to their respective descending lineages.
authors: Department of Molecular Biology, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel. Electronic address: alan.he@huji.ac.il.
authors: Zhiheng
authors: Z
authors: He
authors: Department of Molecular Biology, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
authors: Myriam
authors: M
authors: Grunewald
authors: Department of Molecular Biology, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
authors: Yuval
authors: Y
authors: Dor
authors: Department of Molecular Biology, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel. Electronic address: keshet@cc.huji.ac.il.
authors: Eli
authors: E
authors: Keshet
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D004699:Endocardium / Q000166:cytology / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics*; D013234:Stem Cells / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C063843:insulin gene enhancer binding protein Isl-1
keywords: Flk1; Isl1; Multipotent cardiac progenitors; VEGF