Eph/Ephrin signaling regulates the mesenchymal-to-epithelial transition of the paraxial mesoderm during somite morphogenesis
Eph/Ephrin signaling regulates the mesenchymal-to-epithelial transition of the paraxial mesoderm during somite morphogenesis
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DOI：
10.1016/j.cub.2003.08.030
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发表时间：
2003-09-16
期刊：
影响因子：
9.2
通讯作者：
Wilson, SW
中科院分区：
文献类型：
--
作者：
Barrios, A;Poole, RJ;Wilson, SW
背景资料：在体节发生过程中，基因活动的节段模式提供了间充质细胞上皮化和形成体节的指令。跨膜受体酪氨酸激酶的Eph家族的各种成员及其Ephrin配体在吻端的前体中胚层中以节段模式表达。这种模式在体节沟形成的每个位点建立受体/配体界面。在融合体节（fss/tbx 24）突变体中，缺乏体节间边界和上皮体节伴随着缺乏Eph受体/Ephrin信号传导界面。这些观察表明，Eph/Ephrin信号在体节epithelialization.Results的调节中的作用：我们表明，恢复Eph/Ephrin信号在近轴中胚层的fss突变体拯救体节形态发生的大部分方面。首先，双向或单向EphA 4/Ephrin信号传导的恢复导致形态学上不同的边界的形成和维持。第二，EphA 4的激活导致细胞自主获得柱状形态和P-连环蛋白的顶端再分布，这是体节边界处细胞的上皮化特征的方面。第三，EphA 4的激活导致柱状形态的非自主采集和形成边界的相对侧的细胞中的中心体和细胞核的极化再定位。这些非自主方面的上皮化可能涉及EphA 4与其他intercellular signaling molecules.Conclusions的相互作用：我们的研究结果表明，Eph/Ephrin信号是一个重要的组成部分，驱动体节形态发生的分子机制。我们提出了一个新的作用Eph受体和Ephrin作为细胞间信号分子，建立细胞极性在间充质上皮过渡的近轴中胚层。
Background: During somitogenesis, segmental patterns of gene activity provide the instructions by which mesenchymal cells epithelialize and form somites. Various members of the Eph family of transmembrane receptor tyrosine kinases and their Ephrin ligands are expressed in a segmental pattern in the rostral presomitic mesoderm. This pattern establishes a receptor/ligand interface at each site of somite furrow formation. In the fused somites (fss/tbx24) mutant, lack of intersomitic boundaries and epithelial somites is accompanied by a lack of Eph receptor/Ephrin signaling interfaces. These observations suggest a role for Eph/Ephrin signaling in the regulation of somite epithelialization.Results: We show that restoration of Eph/Ephrin signaling in the paraxial mesoderm of fss mutants rescues most aspects of somite morphogenesis. First, restoration of bidirectional or unidirectional EphA4/Ephrin signaling results in the formation and maintenance of morphologically distinct boundaries. Second, activation of EphA4 leads to the cell-autonomous acquisition of a columnar morphology and apical redistribution of P-catenin, aspects of epithelialization characteristic of cells at somite boundaries. Third, activation of EphA4 leads to nonautonomous acquisition of columnar morphology and polarized relocalization of the centrosome and nucleus in cells on the opposite side of the forming boundary. These nonautonomous aspects of epithelialization may involve interplay of EphA4 with other intercellular signaling molecules.Conclusions: Our results demonstrate that Eph/Ephrin signaling is an important component of the molecular mechanisms driving somite morphogenesis. We propose a new role for Eph receptors and Ephrins as intercellular signaling molecules that establish cell polarity during mesenchymal-to-epithelial transition of the paraxial mesoderm.