Nkx2‐5 lineage tracing visualizes the distribution of second heart field‐derived aortic smooth muscle

During embryonic development, smooth muscle within the ascending aorta arises from two distinct sources: second heart field progenitors and the neural crest. It has recently been hypothesized that the boundary between smooth muscle from these distinct origins may be particularly susceptible to acute aortic dissection. While the contribution of second heart field progenitors to the ascending aorta is well established, detailed mapping of the anatomical distribution of second heart field-derived smooth muscle at this smooth muscle boundary has yet to be observed using a committed cardiac progenitor Cre-lineage. Using Nkx2-5-Cre knockin mice, the anatomical distribution of second heart field derived aortic smooth muscle was mapped in detail. Specifically, Nkx2-5-Cre-labeled cells constitute the entirety of the smooth muscle layer at the aortic base and then become restricted to the adventitial side of the ascending aortic media. This distribution pattern is present by E12.5 in the embryo and persists throughout embryonic development. These data reveal previously unappreciated details regarding the anatomical distribution of second heart field-derived smooth muscle within the aorta as well as the non-cardiomyocyte fates labeled by the Nkx2-5-Cre lineage