Jülich Dörthe, Mould A Paul, Koper Ewa, Holley Scott A
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Development. 2009 Sep;136(17):2913-21. doi: 10.1242/dev.038935. Epub 2009 Jul 29.
Extracellular matrixes (ECMs) coat and subdivide animal tissues, but it is unclear how ECM formation is restricted to tissue surfaces and specific cell interfaces. During zebrafish somite morphogenesis, segmental assembly of an ECM composed of Fibronectin (FN) depends on the FN receptor Integrin alpha5beta1. Using in vivo imaging and genetic mosaics, our studies suggest that incipient Itgalpha5 clustering along the nascent border precedes matrix formation and is independent of FN binding. Integrin clustering can be initiated by Eph/Ephrin signaling, with Ephrin reverse signaling being sufficient for clustering. Prior to activation, Itgalpha5 expressed on adjacent cells reciprocally and non-cell-autonomously inhibits spontaneous Integrin clustering and assembly of an ECM. Surface derepression of this inhibition provides a self-organizing mechanism for the formation and maintenance of ECM along the tissue surface. Within the tissue, interplay between Eph/Ephrin signaling, ligand-independent Integrin clustering and reciprocal Integrin inhibition restricts de novo ECM production to somite boundaries.
细胞外基质（ECM）覆盖并细分动物组织，但目前尚不清楚ECM的形成是如何局限于组织表面和特定细胞界面的。在斑马鱼体节形态发生过程中，由纤连蛋白（FN）组成的ECM的节段性组装依赖于FN受体整合素α5β1。通过体内成像和基因镶嵌技术，我们的研究表明，沿新生边界的初始整合素α5聚集先于基质形成，且独立于FN结合。整合素聚集可由Eph/Ephrin信号传导引发，其中Ephrin反向信号传导足以引发聚集。在激活之前，相邻细胞上表达的整合素α5相互且非细胞自主地抑制整合素的自发聚集和ECM的组装。这种抑制作用的表面去抑制为沿组织表面的ECM形成和维持提供了一种自组织机制。在组织内部，Eph/Ephrin信号传导、非配体依赖性整合素聚集和整合素相互抑制之间的相互作用将新生ECM的产生限制在体节边界。
