Martin Richard Tyler, Bartman Thomas
Division of Pulmonary Biology, Children's Hospital Research Foundation, Cincinnati, Ohio, USA.
Dev Dyn. 2009 Jul;238(7):1796-802. doi: 10.1002/dvdy.21976.
Malformations of the cardiac endocardial cushions (ECs) and valves are common congenital dysmorphisms in newborn infants. Many regulators of EC development have been identified, but the process of valve maturation is less well understood. Zebrafish have been used to understand cardiogenesis through 6 days postfertilization, yet mature heart valves are not present at this stage. By analyzing valve development in larval zebrafish, we identify that valve development proceeds in two phases. Valve elongation occurs through 16 dpf independently of localized cell division. Valve maturation then ensues, resulting from deposition of extracellular matrix and thickening of the valves. Whereas elongation is consistent between larvae, maturation varies based on larval size, suggesting that maturation occurs in response to mechanical forces. Taken together, our studies indicate that zebrafish valve morphogenesis occurs in the larval period, and that zebrafish may provide a unique opportunity to study epigenetic mechanisms leading to human congenital valvular disease, when studied at the appropriate developmental stages.
心脏心内膜垫（ECs）和瓣膜畸形是新生儿常见的先天性畸形。许多EC发育的调节因子已被确定，但瓣膜成熟过程的了解较少。斑马鱼已被用于了解受精后6天内的心脏发生过程，但此时尚未出现成熟的心脏瓣膜。通过分析斑马鱼幼体的瓣膜发育，我们发现瓣膜发育分两个阶段进行。瓣膜伸长在受精后16天内发生，与局部细胞分裂无关。随后瓣膜成熟，这是细胞外基质沉积和瓣膜增厚的结果。虽然幼体之间的伸长是一致的，但成熟程度因幼体大小而异，这表明成熟是对机械力的反应。综上所述，我们的研究表明斑马鱼瓣膜形态发生在幼体期，并且在适当的发育阶段进行研究时，斑马鱼可能为研究导致人类先天性瓣膜疾病的表观遗传机制提供独特的机会。
