Abstract  Angiogenesis process in development is temporally accurate, and involves sprouting, subsequent endothelial cell proliferation, and migration. Tip cells, sensing the extracellular cues, play an important role in this process. Although it is known that several pathways including vascular endothelial growth factor (VEGF) and Notch control tip cell behaviors, the signaling process is largely unknown. Here we showed that an endothelial tyrosine kinase receptor-Tie2 was required for intersegmental vessel (ISV) growth and essential for the sprouting, migration, and proliferation of tip cells with morpholino knockdown strategy in zebrafish. Knockdown of vegf effectively reduced tie2 mRNA level, and tie2 knockdown efficiently blocked the vegf over-expression induced tyrosine kinase receptor-VEGFR1 (flk1) expression, which suggested that the function of Tie2 may be linked to the downstream of VEGF signaling pathway. Furthermore, we found that the embryos displayed normal ISV growth when injected with tie2 or vegf morpholino alone at a low dose, while co-knockdown of them resulted in a severe ISV defect, indicating a synergistic role in ISV formation. These observations demonstrate that Tie2 is an important regulator of tip cell behaviors. Moreover, these findings provide in vivo evidence that Tie2 acts coordinately with Vegf signaling to control angiogenesis.

Keywords   Tie2; angiogenesis; tip cell; Vegf

Received   2014-3-21　　
Accepted  2014-5-14

Funding  This work was supported by the grants from the National Natural Science Foundation of China (81130005) and Ministry of Science and Technology of China (2010CB945600, 2011CB811304).

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