Craniofacial and cardiac development in Xenopus: A genetic approach

描述(由申请人提供)： 我们正在研究参与颅面构型和心脏发育的分子途径，以及它们在先天性疾病病理中的作用。大量影响婴儿的先天性畸形涉及头面部结构或心脏，导致相当大的发病率和死亡率。有趣的是，许多先天性综合征都会导致颅面发育和心脏发育的异常，这表明参与这两个不同器官系统发育的分子信号是共享的。然而，其中许多信号的身份和生物学作用仍然没有得到很好的界定。在这里，我们将在非洲爪哇开发使用正向和反向筛查的遗传方法，并将其与我们两个实验室正在进行的细胞和生化方法相结合，以研究头面部图案形成和心脏发育的遗传控制。公共卫生相关性：我们的主要目标是更好地了解颅面和心脏发育的基本生物学和病理生物学。为此，我们将使用模式生物非洲爪哇进行正向和反向遗传学筛选，以产生人类疾病状态的动物，并识别参与心脏和颅面组织发育的分子途径。

DESCRIPTION (provided by applicant): We are studying the molecular pathways involved in craniofacial patterning and heart development and their role in the pathology of congenital disease. A large number of congenital malformations affecting infants involve either craniofacial structures or the heart, leading to substantial morbidity and mortality. Interestingly, many congenital syndromes result in abnormalities both in craniofacial development and cardiac development suggesting that the molecular signals involved in the development of these two different organ systems are shared. Yet, the identities and the biological roles of many of these signals are still not well defined. Here, we will develop genetic approaches using both a forward and reverse screen in Xenopus that will be integrated with ongoing cellular and biochemical approaches in our two labs to investigate the genetic control of craniofacial pattern formation and heart development. PUBLIC HEALTH RELEVANCE: Our primary goal is to better understand the basic biology and pathobiology of craniofacial and cardiac development. To this end, we will use the model organism Xenopus tropicalis to conduct forward and reverse genetics screens to generate animal for human disease states and to identify the molecular pathways involved in the development of cardiac and craniofacial tissues.