Coronary vessels determine pattern of postganglionic sympathetic innervation in developing heart

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	NHLBI	DEV-8

Authors

• I Onitsuka
• J Nam
• J Hatch
• Y Uchida
• Y Mukoyama

Abstract

Postganglionic sympathetic neurons innervate and control a wide range of target organs including heart and blood vessels, but what instructive environmental signals guide sympathetic axon extension in developing target organs is unknown. We found that in developing heart sympathetic axons extend along with large-diameter coronary veins, which runs on the dorsal surface of the heart. Analysis of mutants suggests that large-diameter coronary veins are necessary for complete sympathetic innervation of developing heart. Since the large-diameter coronary veins are covered with vascular smooth muscle cells (VSMCs), we examined whether VSMCs secret attractive guidance signals to sympathetic axons. In our primary co-culture system of embryonic sympathetic ganglia (SG) explants and fetal epicardium-derived VSMCs, a robust extension of axons from SG explants towards fetal VSMCs, but not towards fetal myocardium, was observed. Gene-expression analysis revealed that Artemin (Artn), Neuregrin1 (Nrg1), and Nerve Growth Factor (Ngf) are preferentially expressed in coronary VSMCs. Among them, loss-of-function experiments using Ngf RNAi and Ngf neutralizing antibody revealed the essential role of Ngf in VSMC-mediated axon guidance. These findings suggest a model in which sympathetic axon pathfindings are controlled by vascular-derived signals in order to further innervate their targets in the developing heart..

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