Vascular Endothelial Growth Factor A (VEGF-A) Is Involved in Guidance of VEGF Receptor-Positive Cells to the Anterior Portion of Early Embryos
Open Access
- 1 January 2005
- journal article
- research article
- Published by Informa UK Limited in Molecular and Cellular Biology
- Vol. 25 (1), 355-363
- https://doi.org/10.1128/mcb.25.1.355-363.2005
Abstract
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 VEGFR1. 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 VEGFR2-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.Keywords
This publication has 65 references indexed in Scilit:
- Autocrine-paracrine VEGF loops potentiate the maturation of megakaryocytic precursors through Flt1 receptorBlood, 2003
- VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cellsOncogene, 1999
- The Phosphorylated 1169-Tyrosine Containing Region of Flt-1 Kinase (VEGFR-1) Is a Major Binding Site for PLCγBiochemical and Biophysical Research Communications, 1997
- The Vascular Endothelial Growth Factor Receptor Flt-1 Mediates Biological ActivitiesJournal of Biological Chemistry, 1996
- Heterozygous embryonic lethality induced by targeted inactivation of the VEGF geneNature, 1996
- Abnormal blood vessel development and lethality in embryos lacking a single VEGF alleleNature, 1996
- Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endotheliumNature, 1995
- Failure of blood-island formation and vasculogenesis in Flk-1-deficient miceNature, 1995
- Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor.Proceedings of the National Academy of Sciences, 1993
- Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factorBiochemical and Biophysical Research Communications, 1992