Dose‐Dependent Transcriptional Regulation by the Calcineurin/NFAT Signaling in Developing Myocardium Transition

Thin spongy myocardium is critical at the early embryonic stage [before embryonic day (E) 13.5 in mice] to allow diffusion of oxygen and nutrient to the developing cardiomyocytes. However, establishment of compact myocardium at later stage (~E16.5) during development is necessary to prepare for the increase in demand for blood circulation. But molecular targets of the spongy‐compact myocardium transition at E13.5–E16.5 in heart development remain elusive. Here, we report transcription targets, independently and dependently, regulated by the calcineurin/NFAT signaling during E13.5–E16.5 myocardium transition. We have uncovered that expression of one‐third of the induced genes during myocardium transition is calcineurin/NFAT dependent. Among these calcineurin/NFAT dependent transcription targets, there is a dose‐dependent regulation. Thus, in addition to temporal and spatial regulation, dose‐dependent threshold requirement provides another mechanism to modulate transcription response mediated by the calcineurin/NFAT signaling. This research is supported, in part, by a grant from the American Heart Association.