Two-step process of sympathetic innervation in the developing heat

Friday, November 08, 2013 — Poster Session IV
2:00 p.m. – 4:00 p.m.	FAES Academic Center (Upper-Level Terrace)	NHLBI	DEVBIO-5

Authors

I Onitsuka
J Hatch
Y Uchida
Y Mukouyama

Abstract

Cardiac tissues are highly vascularized and extensively innervated by autonomic nerves, and proper patterning of cardiac vasculature and autonomic innervation is critical for normal heart function. However, it had been unknown how stereotypical pattern of neuronal and vascular networks develop. Here we show that large diameter coronary veins serve as an intermediate template for distal extension of sympathetic axons. Between embryonic day (E)13.5-15.5, axons extend along with veins in the dorsal subepicardium of the ventricles in the developing mouse heart. Vascular smooth muscle cells (VSMCs) associate with large diameter veins as the vessels undergo vascular remodeling. By in vitro and in ovo experiments, we identified nerve growth factor (NGF) as a VSMC-derived guidance cue that controls the neurovascular association. Further analysis demonstrated that after E15.5, arterial VSMCs in the myocardium start to express NGF as they are recruited by remodeling arteries. This “switch” of NGF expression allows axons to distribute entire ventricle and to reach to the myocardial arteries appropriately. We are currently approaching to clarify the regulatory mechanism of spatiotemporal expression of NGF in venous and arterial VSMCs, which will provide an insight to understand the mechanism that controls distal axon extension and innervation of the target organ.