Coordinate expression of vascular endothelial growth factor receptor-1 (flt-1) and its ligand suggests a paracrine regulation of murine vascular development

G. Breier, Matthias Clauss, W. Risau

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247 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) is a candidate regulator of blood vessel growth during embryonic development and in tumors. To evaluate the role of VEGF receptor-1/fit-1 (VEGFR1/fit-1) in the development of the vascular system, we have characterized the murine homolog of the human fit-1 gene and have analyzed its expression pattern during mouse embryogenesis. Receptor binding studies using transfected COS cells revealed that the murine fit-1 gene encodes a high affinity receptor for VEGF. The apparent K(d) for VEGF binding, as determined by Scatchard analysis, was 114 pM, demonstrating that VEGFR1/flt-1 has a higher affinity to VEGF than VEGF receptor-2/flk-1 (VEGFR2/flk-1). By in situ hybridization, VEGFR1/flt-1 was detected in the yolk sac mesoderm already at the early stages of vascular development, while the receptor ligand was expressed in the entire endoderm of 7.5-day mouse embryos. A comparison with VEGFR2/flk-1 showed that the two receptors shared a common expression domain in the yolk sac mesoderm, but were expressed at different sites in the ectoplacental cone. The differential expression of the two VEGF receptors persisted in the developing placenta, where VEGFR1/flt-1 mRNA was detected in the spongiotrophoblast layer, whereas VEGFR2/flk-1 transcripts were present in the labyrinthine layer which is the site of VEGF expression. In the embryo proper, VEGFR1/flt-1 mRNA was specifically localized in blood vessels and capillaries of the developing organs, closely resembling the pattern of VEGFR2/flk-1 transcript distribution. In the developing brain, the expression of VEGF receptors in the perineural capillary plexus and in capillary sprouts which have invaded the neuroectoderm correlated with endothelial cell proliferation and brain angiogenesis. The data are consistent with the hypothesis that VEGF and its receptors have an important function both in the differentiation of the endothelial lineage and in the neovascularization of developing organs, and act in a paracrine fashion.

Original languageEnglish (US)
Pages (from-to)228-239
Number of pages12
JournalDevelopmental Dynamics
Volume204
Issue number3
StatePublished - 1995
Externally publishedYes

Fingerprint

Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor-2
Vascular Endothelial Growth Factor Receptor
Vascular Endothelial Growth Factor A
Blood Vessels
Ligands
Yolk Sac
Mesoderm
Embryonic Development
Embryonic Structures
Neural Plate
Messenger RNA
Endoderm
COS Cells
Brain
Placenta
Genes
In Situ Hybridization
Endothelial Cells
Cell Proliferation

Keywords

  • Angiogenesis
  • flk-1
  • flt-1
  • Mouse embryo
  • Placenta
  • Vasculogenesis
  • VEGF

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology

Cite this

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title = "Coordinate expression of vascular endothelial growth factor receptor-1 (flt-1) and its ligand suggests a paracrine regulation of murine vascular development",
abstract = "Vascular endothelial growth factor (VEGF) is a candidate regulator of blood vessel growth during embryonic development and in tumors. To evaluate the role of VEGF receptor-1/fit-1 (VEGFR1/fit-1) in the development of the vascular system, we have characterized the murine homolog of the human fit-1 gene and have analyzed its expression pattern during mouse embryogenesis. Receptor binding studies using transfected COS cells revealed that the murine fit-1 gene encodes a high affinity receptor for VEGF. The apparent K(d) for VEGF binding, as determined by Scatchard analysis, was 114 pM, demonstrating that VEGFR1/flt-1 has a higher affinity to VEGF than VEGF receptor-2/flk-1 (VEGFR2/flk-1). By in situ hybridization, VEGFR1/flt-1 was detected in the yolk sac mesoderm already at the early stages of vascular development, while the receptor ligand was expressed in the entire endoderm of 7.5-day mouse embryos. A comparison with VEGFR2/flk-1 showed that the two receptors shared a common expression domain in the yolk sac mesoderm, but were expressed at different sites in the ectoplacental cone. The differential expression of the two VEGF receptors persisted in the developing placenta, where VEGFR1/flt-1 mRNA was detected in the spongiotrophoblast layer, whereas VEGFR2/flk-1 transcripts were present in the labyrinthine layer which is the site of VEGF expression. In the embryo proper, VEGFR1/flt-1 mRNA was specifically localized in blood vessels and capillaries of the developing organs, closely resembling the pattern of VEGFR2/flk-1 transcript distribution. In the developing brain, the expression of VEGF receptors in the perineural capillary plexus and in capillary sprouts which have invaded the neuroectoderm correlated with endothelial cell proliferation and brain angiogenesis. The data are consistent with the hypothesis that VEGF and its receptors have an important function both in the differentiation of the endothelial lineage and in the neovascularization of developing organs, and act in a paracrine fashion.",
keywords = "Angiogenesis, flk-1, flt-1, Mouse embryo, Placenta, Vasculogenesis, VEGF",
author = "G. Breier and Matthias Clauss and W. Risau",
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volume = "204",
pages = "228--239",
journal = "Developmental Dynamics",
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T1 - Coordinate expression of vascular endothelial growth factor receptor-1 (flt-1) and its ligand suggests a paracrine regulation of murine vascular development

AU - Breier, G.

AU - Clauss, Matthias

AU - Risau, W.

PY - 1995

Y1 - 1995

N2 - Vascular endothelial growth factor (VEGF) is a candidate regulator of blood vessel growth during embryonic development and in tumors. To evaluate the role of VEGF receptor-1/fit-1 (VEGFR1/fit-1) in the development of the vascular system, we have characterized the murine homolog of the human fit-1 gene and have analyzed its expression pattern during mouse embryogenesis. Receptor binding studies using transfected COS cells revealed that the murine fit-1 gene encodes a high affinity receptor for VEGF. The apparent K(d) for VEGF binding, as determined by Scatchard analysis, was 114 pM, demonstrating that VEGFR1/flt-1 has a higher affinity to VEGF than VEGF receptor-2/flk-1 (VEGFR2/flk-1). By in situ hybridization, VEGFR1/flt-1 was detected in the yolk sac mesoderm already at the early stages of vascular development, while the receptor ligand was expressed in the entire endoderm of 7.5-day mouse embryos. A comparison with VEGFR2/flk-1 showed that the two receptors shared a common expression domain in the yolk sac mesoderm, but were expressed at different sites in the ectoplacental cone. The differential expression of the two VEGF receptors persisted in the developing placenta, where VEGFR1/flt-1 mRNA was detected in the spongiotrophoblast layer, whereas VEGFR2/flk-1 transcripts were present in the labyrinthine layer which is the site of VEGF expression. In the embryo proper, VEGFR1/flt-1 mRNA was specifically localized in blood vessels and capillaries of the developing organs, closely resembling the pattern of VEGFR2/flk-1 transcript distribution. In the developing brain, the expression of VEGF receptors in the perineural capillary plexus and in capillary sprouts which have invaded the neuroectoderm correlated with endothelial cell proliferation and brain angiogenesis. The data are consistent with the hypothesis that VEGF and its receptors have an important function both in the differentiation of the endothelial lineage and in the neovascularization of developing organs, and act in a paracrine fashion.

AB - Vascular endothelial growth factor (VEGF) is a candidate regulator of blood vessel growth during embryonic development and in tumors. To evaluate the role of VEGF receptor-1/fit-1 (VEGFR1/fit-1) in the development of the vascular system, we have characterized the murine homolog of the human fit-1 gene and have analyzed its expression pattern during mouse embryogenesis. Receptor binding studies using transfected COS cells revealed that the murine fit-1 gene encodes a high affinity receptor for VEGF. The apparent K(d) for VEGF binding, as determined by Scatchard analysis, was 114 pM, demonstrating that VEGFR1/flt-1 has a higher affinity to VEGF than VEGF receptor-2/flk-1 (VEGFR2/flk-1). By in situ hybridization, VEGFR1/flt-1 was detected in the yolk sac mesoderm already at the early stages of vascular development, while the receptor ligand was expressed in the entire endoderm of 7.5-day mouse embryos. A comparison with VEGFR2/flk-1 showed that the two receptors shared a common expression domain in the yolk sac mesoderm, but were expressed at different sites in the ectoplacental cone. The differential expression of the two VEGF receptors persisted in the developing placenta, where VEGFR1/flt-1 mRNA was detected in the spongiotrophoblast layer, whereas VEGFR2/flk-1 transcripts were present in the labyrinthine layer which is the site of VEGF expression. In the embryo proper, VEGFR1/flt-1 mRNA was specifically localized in blood vessels and capillaries of the developing organs, closely resembling the pattern of VEGFR2/flk-1 transcript distribution. In the developing brain, the expression of VEGF receptors in the perineural capillary plexus and in capillary sprouts which have invaded the neuroectoderm correlated with endothelial cell proliferation and brain angiogenesis. The data are consistent with the hypothesis that VEGF and its receptors have an important function both in the differentiation of the endothelial lineage and in the neovascularization of developing organs, and act in a paracrine fashion.

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