Control of extracellular matrix assembly along tissue boundaries via Integrin and Eph/Ephrin signaling

Control of extracellular matrix assembly along tissue boundaries via Integrin and Eph/Ephrin signaling
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DOI:
10.1242/dev.038935
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发表时间:
2009-09-01
期刊:
影响因子:
4.6
通讯作者:
Holley, Scott A.
Holley, Scott A.
中科院分区:
生物学2区
文献类型:
--
作者:
Juelich, Doerthe;Mould, A. Paul;Holley, Scott A.

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细胞外基质(ECM)覆盖和细分动物组织,但目前还不清楚ECM的形成是如何限制在组织表面和特定的细胞界面。在斑马鱼体节形态发生过程中,由纤连蛋白(FN)组成的ECM的节段组装依赖于FN受体整合素α 5 β 1。使用体内成像和遗传镶嵌,我们的研究表明,初期Itg α 5聚类沿着新生的边界之前,基质形成,是独立的FN结合。整联蛋白聚簇可由Eph/Ephrin信号传导启动,其中Ephrin反向信号传导足以用于聚簇。在活化之前,在相邻细胞上表达的Itga 5自主地和非细胞自主地抑制自发的整合素聚集和ECM的组装。这种抑制的表面去抑制提供了一种自组织机制,用于沿着组织表面形成和维持ECM。在组织内,Eph/Ephrin信号传导、配体非依赖性整联蛋白聚集和相互整联蛋白抑制之间的相互作用将从头ECM产生限制到体节边界。
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 alpha 5 beta 1. Using in vivo imaging and genetic mosaics, our studies suggest that incipient Itg alpha 5 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, Itga5 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.