Vascular endothelial growth factor A (VEGF-A) is involved in guidance of VEGF receptor-positive cells to the anterior portion of early embryos
Vascular endothelial growth factor A (VEGF-A) is involved in guidance of VEGF receptor-positive cells to the anterior portion of early embryos
复制标题
DOI：
10.1128/mcb.25.1.355-363.2005
复制
发表时间：
2005-01-01
影响因子：
5.3
通讯作者：
Shibuya, M
中科院分区：
文献类型：
--
作者：
Hiratsuka, S;Kataoka, Y;Shibuya, M
中胚层中的成血管细胞产生成血管细胞和造血干细胞。成血管细胞前体细胞在胎儿躯干中的运动是早期胚胎发生的关键事件。血管内皮生长因子（VEGF）信号传导可能参与这种迁移，因为VEGF受体（VEGFR）阳性细胞在VEGFR 2缺失小鼠或具有截短的VEGFR 1的小鼠中积聚和迁移受到部分干扰。然而，目前尚不清楚VEGF系统如何调节这种迁移或其方向。我们在这里表明，VEGF-A的表达是占主导地位的胚胎的前部，而VEGFR 1。和VEGFR 2在胚胎的后部表达。一种VEGFR激酶抑制剂阻断了全胚胎培养系统中VEGFR阳性细胞的迁移。此外，VEGF阳性细胞在体外向VEGFR 1或VEGFR 2特异性配体迁移。此外，来自野生型或VEGFR 2（+/-）小鼠的VEGFR阳性细胞向前快速移动，而来自携带截短的VEGFR 1 [VEGFR 1（TM-TK）（-/-）]的VEGFR 2（+/-）小鼠的细胞在注射到野生型小鼠中时几乎不迁移。这些结果表明，集中在前部区域的VEGF-A蛋白通过与小鼠胚胎中的VEGFR相互作用，在将VEGFR阳性细胞从后部引导至头部区域中起重要作用。
The hemangioblast in the mesoderm gives rise to both angioblasts and hematopoietic stem cells. The movement of hemangioblast precursor cells in the fetal trunk is a critical event in early embryogenesis. Vascular endothelial growth factor (VEGF) signaling is likely involved in this migration given the partial disturbance of VEGF receptor (VEGFR)-positive cell accumulation and migration in VEGFR2 null mice or mice with a truncated VIEGFR1. However, it is not clear how the VEGF system regulates this migration or its direction. We show here that the expression of VEGF-A is dominant in the anterior portion of the embryo, whereas VEGFR1. and VEGFR2 are expressed in the posterior portion of the embryo. An inhibitor of VEGFR kinase blocked the migration of VEGFR-positive cells in a whole-embryo culture system. In addition, VEGFR-positive cells migrated toward a VEGFR1- or VIEGFR2-specific ligand in vitro. Furthermore, VEGFR-positive cells derived from wild-type or VEGFR2(+/-) mice moved rapidly anteriorly, whereas cells derived from VEGFR2(+/-) mice carrying a truncated VEGFR1 [VEGFR1(TM-TK)(-/-)] migrated little when injected into wild-type mice. These results suggest that the VEGF-A protein concentrated in the anterior region plays an important role in the guidance of VEGFR-positive cells from the posterior portion to the head region by interacting with VEGFR in the mouse embryo.