Davy Alice, Aubin Josée, Soriano Philippe
Program in Developmental Biology, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Genes Dev. 2004 Mar 1;18(5):572-83. doi: 10.1101/gad.1171704.
Eph receptors and ephrin ligands are key players in many developmental processes including embryo patterning, angiogenesis, and axon guidance. Eph/ephrin interactions lead to the generation of a bidirectional signal, in which both the Eph receptors and the ephrins activate downstream signaling cascades simultaneously. To understand the role of ephrin-B1 and the importance of ephrin-B1-induced reverse signaling during embryonic development, we have generated mouse lines carrying mutations in the efnb1 gene. Complete ablation of ephrin-B1 resulted in perinatal lethality associated with a range of phenotypes, including defects in neural crest cell (NCC)-derived tissues, incomplete body wall closure, and abnormal skeletal patterning. Conditional deletion of ephrin-B1 demonstrated that ephrin-B1 acts autonomously in NCCs, and controls their migration. Last, a mutation in the PDZ binding domain indicated that ephrin-B1-induced reverse signaling is required in NCCs. Our results demonstrate that ephrin-B1 acts both as a ligand and as a receptor in a tissue-specific manner during embryogenesis.
Eph受体和ephrin配体是许多发育过程中的关键参与者，包括胚胎模式形成、血管生成和轴突导向。Eph/ephrin相互作用导致双向信号的产生，其中Eph受体和ephrin同时激活下游信号级联反应。为了了解ephrin-B1在胚胎发育过程中的作用以及ephrin-B1诱导的反向信号传导的重要性，我们构建了携带efnb1基因突变的小鼠品系。完全缺失ephrin-B1导致围产期致死，并伴有一系列表型，包括神经嵴细胞（NCC）衍生组织的缺陷、体壁闭合不完全和骨骼模式异常。条件性缺失ephrin-B1表明ephrin-B1在NCC中自主发挥作用，并控制其迁移。最后，PDZ结合结构域的突变表明NCC中需要ephrin-B1诱导的反向信号传导。我们的结果表明，ephrin-B1在胚胎发生过程中以组织特异性方式既作为配体又作为受体发挥作用。
