Ephrin-B1 reverse signaling in craniofacial development

描述（由申请人提供）：颅面发育过程中控制神经嵴迁移的机制尚不清楚。Eph/Ephrin细胞信号传导受体-配体对已被鉴定为在发育过程中发挥关键作用，包括控制神经嵴细胞（NCC）迁移。肝配蛋白-B配体也能够凭借其细胞质C-末端PDZ结合结构域转导反向信号传导。在ephrin-B1的情况下，这种通过PDZ结合结构域的反向信号传导对于神经嵴细胞的适当迁移和正常颅面发育至关重要。这项申请有两个具体目标。首先，我建议确定和表征介质ephrin-B1反向信号在颅面发育过程中使用免疫沉淀法在NCC。其次，我建议识别和功能特性的肝配蛋白-B1反向信号的转录靶点诱导反向信号使用可溶性EphB 2-Fc融合受体在原代NCC文化和比较表达谱。本申请的目的是了解颅面发育过程中ephrin-B1反向信号传导的分子机制。

DESCRIPTION (provided by applicant): The mechanisms controlling neural crest migration during craniofacial development are not well understood. The Eph/Ephrin cell signaling receptor-ligand pair has been identified as playing crucial roles during development, including controlling neural crest cell (NCC) migration. The ephrin-B ligands are also capable of transducing reverse signaling by virtue of their cytoplasmic C-terminal PDZ binding domain. In the case of ephrin-B1, this reverse signaling via the PDZ-binding domain is crucial for the proper migration of neural crest cells and normal craniofacial development. There are two specific aims for this application. First, I propose to identify and characterize mediators of ephrin-B1 reverse signaling during craniofacial development using an immunoprecipitation approach in NCCs. Second, I propose to identify and functionally characterize transcriptional targets of ephrin-B1 reverse signaling by inducing reverse signaling using a soluble EphB2-Fc fusion receptor in primary NCC culture and comparing expression profiles. The goal of this application is to understand molecular mechanisms of ephrin-B1 reverse signaling during craniofacial development.