Local cues trigger changes in the migratory behavior of lymphangioblasts

淋巴管系统由内皮细胞组成，控制着体液平衡、脂肪吸收和免疫监视的重要方面。在胚胎发育过程中，未来的淋巴管内皮细胞在斑马鱼和小鼠中都表现出复杂的迁移行为模式，并且需要在不同的时间点做出各种决定，决定最终构成专利淋巴管脉管系统网络之前采取哪些路线。淋巴管内皮细胞与其环境中细胞之间信号平台的形成、定位和动态行为目前知之甚少。特别是在淋巴管生成的最初阶段，细胞-细胞和细胞-基质界面的研究还不够，迁移的淋巴管内皮细胞的极化行为的分子和机制原因仍然是谜。在目前的项目中，我们将研究一种新发现的分泌蛋白SVEP 1/Polydom如何控制淋巴管内皮细胞的行为。SVEP 1/Polydom蛋白是一种可能构成细胞外基质一部分的大分泌蛋白，不是由内皮细胞表达，而是由其紧邻的其他细胞表达。由于早期淋巴细胞迁移过程中的明显缺陷，斑马鱼和小鼠的基因突变体都表现出致命的淋巴表型。通过采用体内成像，免疫组织化学，肌动蛋白动力学测量，遗传相互作用和细胞培养研究的组合，我们的目标是解开如何内皮细胞和相邻细胞通过动态细胞-细胞和细胞-基质平台在脊椎动物胚胎淋巴管生成。

The lymphatic vascular system is lined by endothelial cells and controls fluid homeostasis, fat absorption and important aspects of immune surveillance. During embryogenesis, future lymphatic endothelial cells exhibit a complex migratory behavioral pattern in both zebrafish and mice, and need to make various decisions at different points in time about which routes to take before eventually constituting a patent lymphatic vasculature network. The formation, localization, and dynamic behavior of signaling platforms between lymphatic endothelial cells and cells in their environment is currently very poorly understood. Particularly during the very first steps of lymphangiogenesis, cell-cell and cell-matrix interfaces are insufficiently studied, and the molecular and mechanistic causes for the polarized behavior of migrating lymphatic endothelial cells remain enigmatic. In the current project, we will investigate how a newly identified secreted protein, SVEP1/Polydom, governs the behavior of lymphatic endothelial cells. The SVEP1/Polydom protein, a large secreted protein that likely constitutes a part of the extracellular matrix, is expressed not by endothelial cells but rather by other cells in their immediate vicinity. Both zebrafish and mouse mutants for the gene exhibit a lethal lymphatic phenotype, due to marked defects during early lymphatic cell migration. By employing a combination of in vivo imaging, immunohistochemistry, measuring actin dynamics, genetic interaction and cell culture studies, we aim to unravel how endothelial cells and neighboring cells communicate through dynamic cell-cell and cell-matrix platforms during vertebrate embryonic lymphangiogenesis.