Department of Cell Biology, Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
Dev Cell. 2011 Aug 16;21(2):301-14. doi: 10.1016/j.devcel.2011.06.033. Epub 2011 Jul 28.
Sprouting angiogenesis expands the embryonic vasculature enabling survival and homeostasis. Yet how the angiogenic capacity to form sprouts is allocated among endothelial cells (ECs) to guarantee the reproducible anatomy of stereotypical vascular beds remains unclear. Here we show that Sema-PlxnD1 signaling, previously implicated in sprout guidance, represses angiogenic potential to ensure the proper abundance and stereotypical distribution of the trunk's segmental arteries (SeAs). We find that Sema-PlxnD1 signaling exerts this effect by antagonizing the proangiogenic activity of vascular endothelial growth factor (VEGF). Specifically, Sema-PlxnD1 signaling ensures the proper endothelial abundance of soluble flt1 (sflt1), an alternatively spliced form of the VEGF receptor Flt1 encoding a potent secreted decoy. Hence, Sema-PlxnD1 signaling regulates distinct but related aspects of angiogenesis: the spatial allocation of angiogenic capacity within a primary vessel and sprout guidance.
发芽血管生成扩展了胚胎脉管系统，使胚胎能够存活和维持体内平衡。然而，内皮细胞（ECs）之间形成芽的血管生成能力是如何分配的，以保证典型血管床的可重复解剖结构仍然不清楚。在这里，我们表明，先前涉及芽引导的 Sema-PlxnD1 信号会抑制血管生成潜力，以确保主干的节段性动脉（SeA）的适当丰度和典型分布。我们发现，Sema-PlxnD1 信号通过拮抗血管内皮生长因子（VEGF）的促血管生成活性来发挥这种作用。具体来说，Sema-PlxnD1 信号确保了可溶性 flt1（sflt1）的适当内皮丰度，sflt1 是 VEGF 受体 Flt1 的一种选择性剪接形式，编码一种有效的分泌诱饵。因此，Sema-PlxnD1 信号调节血管生成的不同但相关方面：主脉内血管生成能力的空间分配和芽引导。
