Cardiac morphogenesis is a carefully orchestrated process representing the first organogenesis milestone in developing vertebrate embryos. Establishment of specific characteristics of two major cardiac chambers, a ventricle and an atrium, is crucial to formation of a functional heart. Despite the importance of maintaining unique features in chamber-specific cardiomyocytes, the regulatory mechanisms guiding these processes are yet to be uncovered. The strong association of NKX2-5 with human congenital heart disease in both chambers and our studies revealing the differential effects of nkx genes on ventricular and atrial cell number in zebrafish prompted our interest in the role of Nkx genes on chamber identity. By exploiting the experimental benefits of the zebrafish model, we have shown that ventricular cardiomyocytes transdifferentiate into atrial cardiomyocytes in the absence of nkx gene function, highlighting the malleable nature of differentiated myocardium. We propose that the newly revealed functions of Nkx genes in preserving chamber-specific traits will help to explain the molecular, cellular, and electrophysiological phenotypes in models of Nkx2-5 deficiency. In the long-term, these studies have potential to shed light on etiologies of fetal and neonatal cardiac pathology and to drive innovations in regenerative medicine.
Targoff, K.L., Schell, T., Yelon, D
Nkx Genes Regulate Heart Tube Extension in Zebrafish and Exert Differential Effects on Ventricular and Atrial Cell Number. Developmental Biology 322(2): 314-321 . (2008.)
Targoff, K.L., Gersony, W.M.
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Chen, J.M., Mosca, R.S., Altmann, K., Printz, B.F., Targoff, K.L., Mazzeo, P.A., Quaegebeur, J.M.
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