Localised Collagen2a1 secretion supports lymphatic endothelial cell migration in the zebrafish embryo
Localised Collagen2a1 secretion supports lymphatic endothelial cell migration in the zebrafish embryo
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DOI：
10.1242/dev.190983
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发表时间：
2020-09-01
期刊：
影响因子：
4.6
通讯作者：
Bower, Neil, I
中科院分区：
文献类型：
--
作者：
Chaudhury, Smrita;Okuda, Kazuhide S.;Bower, Neil, I
淋巴管系统主要从预先存在的静脉发展而来。淋巴管内皮细胞（LECs）首先从主静脉发芽，然后迁移和增殖，以殖民胚胎组织。虽然我们对LEC的命运和早期淋巴管生成过程中的发芽的分子调控了解很多，但我们对支持LEC通过胚胎迁移的指导性和许可性信号知之甚少。使用正向遗传筛选，我们确定了mbtps 1和sec 23 a，COP-II蛋白分泌途径的组成部分，为发展中的淋巴管生成所必需的。在这两种突变体中，LEC最初离开主静脉，但随后在其持续的迁移中失败。在两种突变体中未能分泌的关键货物是II型胶原（Col 2a 1）。Col 2a 1通常由脊索鞘细胞分泌，LEC沿着脊索鞘细胞迁移。col 2a 1a突变体显示LEC迁移行为的缺陷和淋巴管生成失败。因此，这些研究确定Col 2a 1作为脊索鞘细胞分泌的关键货物，并需要LEC的迁移。这些发现联合收割机与我们目前的理解表明，连续的细胞-细胞和细胞-基质相互作用调节LEC迁移通过胚胎环境在发展过程中。
The lymphatic vasculature develops primarily from pre-existing veins. A pool of lymphatic endothelial cells (LECs) first sprouts from cardinal veins followed by migration and proliferation to colonise embryonic tissues. Although much is known about the molecular regulation of LEC fate and sprouting during early lymphangiogenesis, we know far less about the instructive and permissive signals that support LEC migration through the embryo. Using a forward genetic screen, we identified mbtps1 and sec23a, components of the COP-II protein secretory pathway, as essential for developmental lymphangiogenesis. In both mutants, LECs initially depart the cardinal vein but then fail in their ongoing migration. A key cargo that failed to be secreted in both mutants was a type II collagen (Col2a1). Col2a1 is normally secreted by notochord sheath cells, alongside which LECs migrate. col2a1a mutants displayed defects in the migratory behaviour of LECs and failed lymphangiogenesis. These studies thus identify Col2a1 as a key cargo secreted by notochord sheath cells and required for the migration of LECs. These findings combine with our current understanding to suggest that successive cell-to-cell and cell-matrix interactions regulate the migration of LECs through the embryonic environment during development.