Zebrafish Crip2 plays a critical role in atrioventricular valve development by downregulating the expression of ECM genes in the endocardial cushion.
The initial step of atrioventricular (AV) valve development involves the deposition of extracellular matrix (ECM) components of the endocardial cushion and the endocardial-mesenchymal transition. While the appropriately regulated expression of the major ECM components, Versican and Hyaluronan, that form the endocardial cushion is important for heart valve development, the underlying mechanism that regulates ECM gene expression remains unclear. We found that zebrafish crip2 expression is restricted to a subset of cells in the AV canal (AVC) endocardium at 55 hours post-fertilization (hpf). Knockdown of crip2 induced a heart-looping defect in zebrafish embryos, although the development of cardiac chambers appeared to be normal. In the AVC of Crip2-deficient embryos, the expression of both versican a and hyaluronan synthase 2 (has2) was highly upregulated, but the expression of bone morphogenetic protein 4 (bmp4) and T-box 2b (tbx2b) in the myocardium and of notch1b in the endocardium in the AVC did not change. Taken together, these results indicate that crip2 plays an important role in AV valve development by downregulating the expression of ECM components in the endocardial cushion.
Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
Jun-Dae
JD
Kim
School of Life Science and Biotechnology (Brain Korea 21 plus program), Kyungpook National University, Daegu 702-701, Korea.
Hey-Jin
HJ
Kim
Soonil
S
Koun
Hyung-Jin
HJ
Ham
Myoung-Jin
MJ
Kim
Department of Biological Sciences, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 305-764, Korea.
Myungchull
M
Rhee
Korea Basic Science Institute Daegu Center, Daegu 702-701, Korea.
Tae-Lin
TL
Huh
D000818:Animals; D015536:Down-Regulation; D054089:Endocardial Cushions / Q000196:embryology / Q000378:metabolism*; D004699:Endocardium / Q000196:embryology* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006351:Heart Valves / Q000196:embryology*; D060588:LIM Domain Proteins / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000502:physiology*
C528531:CRIP2 protein, zebrafish; D016326:Extracellular Matrix Proteins; D060588:LIM Domain Proteins; D029961:Zebrafish Proteins