VEGF regulates relative allocation of Isl1+ cardiac progenitors to myocardial and endocardial lineages

Zhiheng He*, Myriam Grunewald, Yuval Dor, Eli Keshet

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageAmerican English
Pages (from-to)40-49
Number of pages10
JournalMechanisms of Development
Volume142
DOIs
StatePublished - 1 Nov 2016

Bibliographical note

Publisher Copyright:
© 2016

Keywords

  • Flk1
  • Isl1
  • Multipotent cardiac progenitors
  • VEGF

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