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Publication : VEGF regulates relative allocation of Isl1<sup>+</sup> cardiac progenitors to myocardial and endocardial lineages.

First Author  He Z Year  2016
Journal  Mech Dev Volume  142
Pages  40-49 PubMed ID  27794491
Mgi Jnum  J:237539 Mgi Id  MGI:5812866
Doi  10.1016/j.mod.2016.10.004 Citation  He Z, et al. (2016) VEGF regulates relative allocation of Isl1+ cardiac progenitors to myocardial and endocardial lineages. Mech Dev 142:40-49
abstractText  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.
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