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Venous endothelin guides sympathetic innervation of the developing mouse heart

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  • Eleana Manousiouthakis

    (Developmental Neuroscience Program, The Saban Research Institute, Children’s Hospital Los Angeles, University of Southern California Keck School of Medicine)

  • Monica Mendez

    (Developmental Neuroscience Program, The Saban Research Institute, Children’s Hospital Los Angeles, University of Southern California Keck School of Medicine)

  • Madeline C. Garner

    (Developmental Neuroscience Program, The Saban Research Institute, Children’s Hospital Los Angeles, University of Southern California Keck School of Medicine)

  • Prisca Exertier

    (Developmental Neuroscience Program, The Saban Research Institute, Children’s Hospital Los Angeles, University of Southern California Keck School of Medicine)

  • Takako Makita

    (Developmental Neuroscience Program, The Saban Research Institute, Children’s Hospital Los Angeles, University of Southern California Keck School of Medicine)

Abstract

The mechanisms responsible for establishing correct target innervation during organ development are largely unknown. Sympathetic nerves follow blood vessels—typically arteries—to reach their endorgans, suggesting the existence of vascular guidance cues that direct axonal extension. The sinoatrial node and the ventricle of the heart receive sympathetic innervation from the stellate ganglia (STG). Here we show that STG axons follow veins, specifically the superior vena cavae and sinus venosus, to reach these targets. We find that election of these routes is determined by venous endothelium-derived endothelin-1, acting through its specific receptor Ednra expressed within a subpopulation of STG neurons. Furthermore, we demonstrate that Edn1–Ednra signalling is essential for functional regulation of the heart by sympathetic nerves. Our findings present venous Edn1 as a sympathetic guidance cue, and show how axon guidance mechanisms are coordinated with endorgan morphogenesis.

Suggested Citation

  • Eleana Manousiouthakis & Monica Mendez & Madeline C. Garner & Prisca Exertier & Takako Makita, 2014. "Venous endothelin guides sympathetic innervation of the developing mouse heart," Nature Communications, Nature, vol. 5(1), pages 1-9, September.
  • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4918
    DOI: 10.1038/ncomms4918
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