The Development of Coronary Vascular Network Precedes and Guides the Patterning of Cardiac Nerves

Abstract

Coronary vessels and cardiac peripheral nerves are highly branched structures. Developmental processes involved in the patterning of these structures are not known. Here, we investigated if the formation of these two networks is independent or related process. Complete coronary structures emerge at E14.5 as the vessels undergo remodeling. However, peripheral nerves at this stage only begin to appear at the base of heart, suggesting nerves do not guide the patterning of the vessels. Peripheral nerve coverage is completed by E15.5, as demonstrated by the nerves reaching to the apex. These nerves are originated from a few ganglia around the aorta, trachea, and septum primum. The nerves following the paths of large‐diameter coronary veins become prominent in thickness and size as the heart develops further. The close alignment of the nerves to coronary veins suggests that the veins may provide patterning signal for the nerves. Preliminary data from two mutant mice support such notion. First, the heart of c‐myb DNA binding mutant shows misrouted coronary veins. Remarkably, the nerves follow the misrouted vessels in the mutant. Second, the heart of Sema3A mutant shows disorganized nerves. But the coronary veins do not follow the nerves. These observations suggest that coronary veins guides the patterning of peripheral nerves. This work was supported by the National Heart, Lung, and Blood Institute, NIH.