Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis

T. O. Ishikawa, Y. Tamai, A. M. Zorn, H. Yoshida, Michael F Seldin, S. I. Nishikawa, M. M. Taketo

Research output: Contribution to journalArticle

245 Citations (Scopus)

Abstract

Wnts are secreted signaling molecules implicated in various developmental processes and frizzled proteins are the receptors for these Wnt ligands. To investigate the physiological roles of frizzled proteins, we isolated and characterized a novel mouse frizzled gene Fzd5. Fzd5 mRNA was expressed in the yolk sac, eye and lung bud at 9.5 days post coitum. Fzd5 specifically synergized with Wnt2, Wnt5a and Wnt10b in ectopic axis induction assays in Xenopus embryos. Using homologous recombination in embryonic stem cells, we have generated Fzd5 knockout mice. While the heterozygotes were viable, fertile and appeared normal, the homozygous embryos died in utero around 10.75 days post coitum, owing to defects in yolk sac angiogenesis. At 10.25 days post coitum, prior to any morphological changes, endothelial cell proliferation was markedly reduced in homozygous mutant yolk sacs, as measured by BrdU labeling. By 10.75 days post coitum, large vitelline vessels were poorly developed, and the capillary plexus was disorganized. At this stage, vasculogenesis in the placenta was also defective, although that in the embryo proper was normal. Because Wnt5a and Wnt10b co-localized with Fzd5 in the developing yolk sac, these two Wnts are likely physiological ligands for the Fzd5-dependent signaling for endothelial growth in the yolk sac.

Original languageEnglish (US)
Pages (from-to)25-33
Number of pages9
JournalDevelopment
Volume128
Issue number1
StatePublished - 2001
Externally publishedYes

Fingerprint

Wnt Receptors
Yolk Sac
Frizzled Receptors
Embryonic Structures
Genes
Ligands
Homologous Recombination
Bromodeoxyuridine
Embryonic Stem Cells
Heterozygote
Xenopus
Knockout Mice
Placenta
Endothelial Cells
Cell Proliferation
Lung
Messenger RNA
Growth

Keywords

  • Axis specification
  • Frizzled
  • Gene targeting
  • Mouse
  • Wnt

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Ishikawa, T. O., Tamai, Y., Zorn, A. M., Yoshida, H., Seldin, M. F., Nishikawa, S. I., & Taketo, M. M. (2001). Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis. Development, 128(1), 25-33.

Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis. / Ishikawa, T. O.; Tamai, Y.; Zorn, A. M.; Yoshida, H.; Seldin, Michael F; Nishikawa, S. I.; Taketo, M. M.

In: Development, Vol. 128, No. 1, 2001, p. 25-33.

Research output: Contribution to journalArticle

Ishikawa, TO, Tamai, Y, Zorn, AM, Yoshida, H, Seldin, MF, Nishikawa, SI & Taketo, MM 2001, 'Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis', Development, vol. 128, no. 1, pp. 25-33.
Ishikawa TO, Tamai Y, Zorn AM, Yoshida H, Seldin MF, Nishikawa SI et al. Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis. Development. 2001;128(1):25-33.
Ishikawa, T. O. ; Tamai, Y. ; Zorn, A. M. ; Yoshida, H. ; Seldin, Michael F ; Nishikawa, S. I. ; Taketo, M. M. / Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis. In: Development. 2001 ; Vol. 128, No. 1. pp. 25-33.
@article{75b1e50ce89b48d9b49047593b0afbf0,
title = "Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis",
abstract = "Wnts are secreted signaling molecules implicated in various developmental processes and frizzled proteins are the receptors for these Wnt ligands. To investigate the physiological roles of frizzled proteins, we isolated and characterized a novel mouse frizzled gene Fzd5. Fzd5 mRNA was expressed in the yolk sac, eye and lung bud at 9.5 days post coitum. Fzd5 specifically synergized with Wnt2, Wnt5a and Wnt10b in ectopic axis induction assays in Xenopus embryos. Using homologous recombination in embryonic stem cells, we have generated Fzd5 knockout mice. While the heterozygotes were viable, fertile and appeared normal, the homozygous embryos died in utero around 10.75 days post coitum, owing to defects in yolk sac angiogenesis. At 10.25 days post coitum, prior to any morphological changes, endothelial cell proliferation was markedly reduced in homozygous mutant yolk sacs, as measured by BrdU labeling. By 10.75 days post coitum, large vitelline vessels were poorly developed, and the capillary plexus was disorganized. At this stage, vasculogenesis in the placenta was also defective, although that in the embryo proper was normal. Because Wnt5a and Wnt10b co-localized with Fzd5 in the developing yolk sac, these two Wnts are likely physiological ligands for the Fzd5-dependent signaling for endothelial growth in the yolk sac.",
keywords = "Axis specification, Frizzled, Gene targeting, Mouse, Wnt",
author = "Ishikawa, {T. O.} and Y. Tamai and Zorn, {A. M.} and H. Yoshida and Seldin, {Michael F} and Nishikawa, {S. I.} and Taketo, {M. M.}",
year = "2001",
language = "English (US)",
volume = "128",
pages = "25--33",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "1",

}

TY - JOUR

T1 - Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis

AU - Ishikawa, T. O.

AU - Tamai, Y.

AU - Zorn, A. M.

AU - Yoshida, H.

AU - Seldin, Michael F

AU - Nishikawa, S. I.

AU - Taketo, M. M.

PY - 2001

Y1 - 2001

N2 - Wnts are secreted signaling molecules implicated in various developmental processes and frizzled proteins are the receptors for these Wnt ligands. To investigate the physiological roles of frizzled proteins, we isolated and characterized a novel mouse frizzled gene Fzd5. Fzd5 mRNA was expressed in the yolk sac, eye and lung bud at 9.5 days post coitum. Fzd5 specifically synergized with Wnt2, Wnt5a and Wnt10b in ectopic axis induction assays in Xenopus embryos. Using homologous recombination in embryonic stem cells, we have generated Fzd5 knockout mice. While the heterozygotes were viable, fertile and appeared normal, the homozygous embryos died in utero around 10.75 days post coitum, owing to defects in yolk sac angiogenesis. At 10.25 days post coitum, prior to any morphological changes, endothelial cell proliferation was markedly reduced in homozygous mutant yolk sacs, as measured by BrdU labeling. By 10.75 days post coitum, large vitelline vessels were poorly developed, and the capillary plexus was disorganized. At this stage, vasculogenesis in the placenta was also defective, although that in the embryo proper was normal. Because Wnt5a and Wnt10b co-localized with Fzd5 in the developing yolk sac, these two Wnts are likely physiological ligands for the Fzd5-dependent signaling for endothelial growth in the yolk sac.

AB - Wnts are secreted signaling molecules implicated in various developmental processes and frizzled proteins are the receptors for these Wnt ligands. To investigate the physiological roles of frizzled proteins, we isolated and characterized a novel mouse frizzled gene Fzd5. Fzd5 mRNA was expressed in the yolk sac, eye and lung bud at 9.5 days post coitum. Fzd5 specifically synergized with Wnt2, Wnt5a and Wnt10b in ectopic axis induction assays in Xenopus embryos. Using homologous recombination in embryonic stem cells, we have generated Fzd5 knockout mice. While the heterozygotes were viable, fertile and appeared normal, the homozygous embryos died in utero around 10.75 days post coitum, owing to defects in yolk sac angiogenesis. At 10.25 days post coitum, prior to any morphological changes, endothelial cell proliferation was markedly reduced in homozygous mutant yolk sacs, as measured by BrdU labeling. By 10.75 days post coitum, large vitelline vessels were poorly developed, and the capillary plexus was disorganized. At this stage, vasculogenesis in the placenta was also defective, although that in the embryo proper was normal. Because Wnt5a and Wnt10b co-localized with Fzd5 in the developing yolk sac, these two Wnts are likely physiological ligands for the Fzd5-dependent signaling for endothelial growth in the yolk sac.

KW - Axis specification

KW - Frizzled

KW - Gene targeting

KW - Mouse

KW - Wnt

UR - http://www.scopus.com/inward/record.url?scp=0035155579&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035155579&partnerID=8YFLogxK

M3 - Article

VL - 128

SP - 25

EP - 33

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 1

ER -