Expression of Netrin-1 in the developing mouse heart

Axon guidance signaling pathways, including the Eph/ephrin, Semaphorin, and Slit/Robo pathways, have been found to play crucial roles in cardiac development. Netrin signaling is another well-studied signaling pathway important for axon guidance, but its role in the developing heart has not been investigated. Here, we describe the novel expression pattern of Netrin-1 in the developing murine heart. Transcriptomic analysis of embryonic mouse hearts shows dynamic Netrin-1 expression from E8.5 through E14.5, where Netrin-1 expression preferentially co-localizes with developing trabecular cardiomyocytes. We further demonstrate the spatiotemporal expression pattern of Netrin-1 using a combination of RNA in situ hybridization and Netrin-1^Bgeo/+ reporter mice. Netrin-1 is expressed in the developing cardiomyocytes with the highest degree of expression within the left ventricular trabecular myocardium, which has not been previously recognized. Additionally, Netrin-1 expression is observed at lower levels in the cardiomyocytes of the right ventricle and atria. This expression pattern supports a role for Netrin signaling in the developing murine myocardium requiring further functional characterization.