Department of Cell and Developmental Biology, Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Ann N Y Acad Sci. 2010 Feb;1188:184-90. doi: 10.1111/j.1749-6632.2009.05099.x.
Congenital heart disease represents the most common form of human birth defect, occurring in nearly 1 in 100 live births. An increasing number of patients with these defects are surviving infancy. Approximately one-third of congenital heart defects involve malformations of the outflow tract. Related defects are found in isolation and as part of common human syndromes. Our laboratory has investigated mechanisms of cardiac morphogenesis with particular attention to outflow tract formation. During cardiogenesis, neural crest cells interact with second heart field myocardium and endocardial cushion mesenchyme. Our recent work demonstrates that Jagged1/Notch signaling within the second heart field initiates a signaling cascade involving Fgf8, Bmp4, and downstream effectors that modulate outflow tract development and aortic arch artery patterning. Hence, complex tissue-tissue interactions and integration of multiple pathways converge to orchestrate proper patterning of the outflow region. The role of Notch signaling in adult cardiac homeostasis and disease is an area of active investigation.
先天性心脏病是最常见的人类出生缺陷，每 100 例活产中就有近 1 例。越来越多患有这些缺陷的患者能够存活至婴儿期。大约三分之一的先天性心脏病涉及流出道畸形。相关缺陷单独存在，也存在于常见的人类综合征中。我们的实验室研究了心脏形态发生的机制，特别关注流出道的形成。在心脏发生过程中，神经嵴细胞与第二心脏场心肌和心内膜垫间质相互作用。我们最近的工作表明，第二心脏场中的 Jagged1/Notch 信号启动了一个信号级联反应，涉及 Fgf8、Bmp4 和下游效应物，这些物质调节流出道的发育和主动脉弓动脉的模式形成。因此，复杂的组织-组织相互作用和多种途径的整合汇聚在一起，协调流出区域的正确模式形成。Notch 信号在成人心脏稳态和疾病中的作用是一个活跃的研究领域。
