Coronary vasculature patterning requires a novel endothelial ErbB2 holoreceptor

Haig Aghajanian, Young Kuk Cho, Lauren J. Manderfield, Madison R. Herling, Mudit Gupta, Vivienne C. Ho, Li Li, Karl Degenhardt, Alla Aharonov, Eldad Tzahor, Jonathan A. Epstein

Research output: Contribution to journalArticlepeer-review

Abstract

Organogenesis and regeneration require coordination of cellular proliferation, regulated in part by secreted growth factors and cognate receptors, with tissue nutrient supply provided by expansion and patterning of blood vessels. Here we reveal unexpected combinatorial integration of a growth factor co-receptor with a heterodimeric partner and ligand known to regulate angiogenesis and vascular patterning. We show that ErbB2, which can mediate epidermal growth factor (EGF) and neuregulin signalling in multiple tissues, is unexpectedly expressed by endothelial cells where it partners with neuropilin 1 (Nrp1) to form a functional receptor for the vascular guidance molecule semaphorin 3d (Sema3d). Loss of Sema3d leads to improper patterning of the coronary veins, a phenotype recapitulated by endothelial loss of ErbB2. These findings have implications for possible cardiovascular side-effects of anti-ErbB2 therapies commonly used for cancer, and provide an example of integration at the molecular level of pathways involved in tissue growth and vascular patterning.

Original languageEnglish
Article number12038
JournalNature Communications
Volume7
DOIs
StatePublished - 30 Jun 2016

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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