Clin Res Cardiol 100, Suppl 1, April 2011

P652 - Nephronectin regulates heart patterning via BMP4-HAS2 signaling during zebrafish heart development
C. Patra1, F. Diehl1, F. Ferrazzi2, M. J. van Amerongen1, T. Novoyatleva1, B. Jungblut1, F. Engel1
1MPI for heart and lung research, Bad Nauheim; 2Università degli Studi di Pavia, Pavia, Italien;
The extracellular matrix plays an important role in cardiac morphogenesis and heart disease. Here, we describe a novel role of the extracellular matrix protein Nephronectin (Npnt) for zebrafish heart development. In situ hybridization analysis revealed that npnt is transiently expressed in the myocardium. Morpholino-mediated knock down of npnt expression resulted in an extended tube like structure at the atrio-ventricular boundary, defective heart-looping and pericardial edema. These phenotypes could be rescued by injection of npnt mRNA. Additionally, expression of genes important for atrio-ventricular canal differentiation (has2, cspg2, fibulin1, tbx2b, bmp4) was expanded in npnt morphants. Moreover, npnt morphants exhibited an increased number of endocardial cells with atrio-ventricular canal characteristics (notch1b- and Alcam-positive, cuboidal shape). Inhibition of has2 in wildtype and npnt morphant embryos reduced the number of notch1b- and Alcam-positive cells without affecting bmp4 expression in the myocardium. Inhibition of BMP signaling in npnt morphant reduced ectopic expression of has2, notch1b, cspg2 and Alcam. Taken together, our results identify Nephronectin as a novel regulator of cardiac development upstream of BMP4-HAS2 signaling playing a crucial role in atrio-ventricular canal differentiation in the zebrafish heart.
Clin Res Cardiol 100, Suppl 1, April 2011
Zitierung mit Vortrags- oder Posternummer s.o.
DOI 10.1007/s00392-011-1100-y