Congenital heart defects are some of the most common birth defects. To understand the nature of these defects it is important to study signaling pathways, like Retinoic Acid (RA) signaling, which is required for normal heart development. RA signaling is important for cell differentiation in adult and embryonic tissues. Loss of RA signaling in adult tissues can lead to cancer and in embryos leads to developmental defects. Too much RA signaling can also be teratogenic. Thus, modulation of RA signaling levels is important for proper cell differentiation. The Yelon, using zebrafish, recently discovered a new role for RA signaling in proper cardiomyocyte progenitor selection. Without RA signaling, too many cardiomyocyte progenitors differentiate within a discrete area. The molecular mechanisms that influence cardiomyocyte progenitor selection have not been investigated. Moreover, we are unaware of what is regulating RA signaling. Therefore, the specific aims of my post-doctoral research are: 1) to determine how RA signaling levels affect differentiation of cardiomyocyte progenitors in zebrafish; 2) to determine which RA receptors regulate cardiomyocyte progenitors differentiation; 3) and to identify novel regulators of RA signaling. ? ?
| Waxman, Joshua S; Yelon, Deborah (2011) Zebrafish retinoic acid receptors function as context-dependent transcriptional activators. Dev Biol 352:128-40 |
| Feng, L; Hernandez, R E; Waxman, J S et al. (2010) Dhrs3a regulates retinoic acid biosynthesis through a feedback inhibition mechanism. Dev Biol 338:1-14 |
| Waxman, Joshua S; Yelon, Deborah (2009) Increased Hox activity mimics the teratogenic effects of excess retinoic acid signaling. Dev Dyn 238:1207-13 |
| Waxman, Joshua S; Keegan, Brian R; Roberts, Richard W et al. (2008) Hoxb5b acts downstream of retinoic acid signaling in the forelimb field to restrict heart field potential in zebrafish. Dev Cell 15:923-34 |
| Waxman, Joshua S; Yelon, Deborah (2007) Comparison of the expression patterns of newly identified zebrafish retinoic acid and retinoid X receptors. Dev Dyn 236:587-95 |
