Vegfc is required for vascular development and endoderm morphogenesis in zebrafish
Vegfc is required for vascular development and endoderm morphogenesis in zebrafish
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DOI：
10.1038/sj.embor.7400047
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发表时间：
2004-01-01
期刊：
影响因子：
7.7
通讯作者：
Stainier, DYR
中科院分区：
文献类型：
--
作者：
Ober, EA;Olofsson, B;Stainier, DYR
在胚胎发生期间，复杂的形态发生事件导致内胚层细胞在中线处合并并形成原肠管和相关器官。虽然最近有几个基因被牵连在内胚层分化，我们知道很少的基因，调节内胚层形态发生。在这里，我们表明，血管内皮生长因子C（Vegfc），血管生成以及淋巴管生成因子，出乎意料地参与这一过程中的斑马鱼。使用吗啉代反义寡核苷酸或通过VEGFC受体VEGFR-3的可溶性形式的过表达来降低Vegfc水平，影响前中线中内胚层细胞的聚结，导致分叉肠管的形成以及肝脏和胰腺芽的复制。进一步的分析表明，Vegfc是额外需要的背内胚层的初始形成。我们还证明了Vegfc是斑马鱼胚胎中血管发生和血管生成所必需的。这些数据证明了Vegfc在发育中的脉管系统中的需求，并且更令人惊讶的是，暗示了Vegfc信号传导在内胚层发育期间的两个不同步骤中，第一个是在背侧内胚层的初始分化期间，第二个是在前内胚层向中线的聚结中。
During embryogenesis, complex morphogenetic events lead endodermal cells to coalesce at the midline and form the primitive gut tube and associated organs. While several genes have recently been implicated in endoderm differentiation, we know little about the genes that regulate endodermal morphogenesis. Here, we show that vascular endothelial growth factor C (Vegfc), an angiogenic as well as a lymphangiogenic factor, is unexpectedly involved in this process in zebrafish. Reducing Vegfc levels using morpholino antisense oligonucleotides, or through overexpression of a soluble form of the VEGFC receptor, VEGFR-3, affects the coalescence of endodermal cells in the anterior midline, leading to the formation of a forked gut tube and the duplication of the liver and pancreatic buds. Further analyses indicate that Vegfc is additionally required for the initial formation of the dorsal endoderm. We also demonstrate that Vegfc is required for vasculogenesis as well as angiogenesis in the zebrafish embryo. These data argue for a requirement of Vegfc in the developing vasculature and, more surprisingly, implicate Vegfc signalling in two distinct steps during endoderm development, first during the initial differentiation of the dorsal endoderm, and second in the coalescence of the anterior endoderm to the midline.