![]() ![]() Hence, determining the activity of RA signaling in specific cell types or tissues is challenging, and has traditionally relied on RA reporter lines. ![]() Unlike most other embryonic signals that are peptidic in nature and act through membrane receptors, RA is a very small lipophilic molecule that cannot be easily detected by conventional means ( Rhinn and Dollé, 2012). Once synthesized, RA can activate or repress the transcription of various genes by binding to nuclear retinoic acid receptors (RARA, RARB, RARG), which form heterodimers with retinoid X receptors (RXRA, RXRB, RXRG) ( Niederreither and Dollé, 2008). RA is synthesized in two oxidative steps, with the second step being carried out by three retinaldehyde dehydrogenases (ALDH1A1, ALDH1A2, ALDH1A3). Retinoic acid (RA), the active derivative of vitamin A, plays essential roles in cell growth, differentiation, and organogenesis ( Duester, 2008 Cunningham and Duester, 2015). RNA sequencing analysis reveals Tgm2 and Ace1, two genes with well-established links to cardiac repair, as potential targets of RA signaling in primary cardiomyocytes, thereby providing novel links between the RA pathway and heart disease. Ablation of RA signaling through deletion of the Aldh1a1/a2/a3 genes encoding RA-synthesizing enzymes leads to increased cardiomyocyte apoptosis in adults subjected to MI. Strikingly, we have observed a direct RA response in cardiomyocytes during mid-late gestation and after MI. Here we have developed an inducible murine transgenic RA-reporter line using CreER T2 technology that permits lineage tracing of RA-responsive cells and faithfully recapitulates endogenous RA activity in multiple organs during embryonic development. ![]() In both cases, the effect of RA signaling on cardiomyocytes, the principle cell type of the heart, has been reported to be indirect. Retinoic acid (RA) is an essential signaling molecule for cardiac development and plays a protective role in the heart after myocardial infarction (MI). ![]()
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