Delineating ephrin-B2 mechanisms in morphogenesis of the foregut

 描述(申请人提供)：在发育过程中，气管和食道是通过分离单个前肠上皮管形成的；如果分离失败，就会形成气管和食道的不适当连接或瘘管。尽管前肠发育的先天异常是常见的，但控制这一发育过程的途径还不完全清楚，而且几乎不存在关于分离的分子效应的知识。我们利用一个新的小鼠模型的初步数据表明，efnb2基因可能是这一过程的关键调节因子。EfNB2编码EPhin-B2，它是Eph/eaffin家族细胞信号分子中的一个成员，参与了多种环境中的形态发生。我们将利用小鼠遗传学来剖析组织特异性需求和前肠形态发生中的细胞角色，并开始确定它在控制这一过程的遗传网络中的位置。这些研究代表了一个新的方向，我们将把我们的理解集中在气管-食道分离的影响因素上，从而提高对前肠发育结构性出生缺陷的理解。

 DESCRIPTION (provided by applicant): During development, the trachea and esophagus are formed by separating a single foregut epithelial tube; when this fails an inappropriate connection or fistula of the trachea and esophagus is formed. Despite the common occurrence of congenital anomalies of foregut development, the pathways controlling this developmental process are incompletely understood and almost no knowledge exists regarding the molecular effectors of separation. Our preliminary data utilizing a novel mouse model indicate that the efnb2 gene may be a key regulator of this process. Efnb2 encodes ephrin-B2 a member of the Eph/ephrin family of cell signaling molecules that are involved in morphogenesis in a wide-variety of contexts. We will utilize mouse genetics to dissect the tissue specific requirement and cellular roles of ephrin-B2 in foregut morphogenesis and begin to determine where it fits in the genetic network controlling this process. These studies represent a new direction in which we will focus our understanding on the effectors of tracheoesophageal separation leading to improved understanding of structural birth defects of foregut development.