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Abnormal angiogenesis but intact hematopoietic potential in TGF-beta type I receptor-deficient mice

Larsson, Jonas LU ; Goumans, Marie-José; Jansson Sjöstrand, Lottie LU ; van Rooijen, Marga A.; Ward, Dorien; Levéen, Per LU ; Xu, Xiufeng; ten Dijke, Peter; Mummery, Christine L. and Karlsson, Stefan LU (2001) In EMBO Journal 20(7). p.1663-1673
Abstract
Deletion of the transforming growth factor beta1 (TGF-beta1) gene in mice has previously suggested that it regulates both hematopoiesis and angiogenesis. To define the function of TGF-beta more precisely, we inactivated the TGF-beta type I receptor (T beta RI) gene by gene targeting. Mice lacking T beta RI die at midgestation, exhibiting severe defects in vascular development of the yolk sac and placenta, and an absence of circulating red blood cells. However, despite obvious anemia in the T beta RI-/- yolk sacs, clonogenic assays on yolk sac-derived hematopoietic precursors in vitro revealed that T beta RI-/- mice exhibit normal hematopoietic potential compared with wild-type and heterozygous siblings, Endothelial cells derived from T... (More)
Deletion of the transforming growth factor beta1 (TGF-beta1) gene in mice has previously suggested that it regulates both hematopoiesis and angiogenesis. To define the function of TGF-beta more precisely, we inactivated the TGF-beta type I receptor (T beta RI) gene by gene targeting. Mice lacking T beta RI die at midgestation, exhibiting severe defects in vascular development of the yolk sac and placenta, and an absence of circulating red blood cells. However, despite obvious anemia in the T beta RI-/- yolk sacs, clonogenic assays on yolk sac-derived hematopoietic precursors in vitro revealed that T beta RI-/- mice exhibit normal hematopoietic potential compared with wild-type and heterozygous siblings, Endothelial cells derived from T beta RI-deficient embryos show enhanced cell proliferation, improper migratory behavior and impaired fibronectin production in vitro, defects that are associated with the vascular defects seen in vivo. We thus demonstrate here that, while T beta RI is crucial for the function of TGF-beta during vascular development and can not be compensated for by the activin receptor-like kinase-1 (ALK-1), functional hematopoiesis and development of hematopoietic progenitors is not dependent on TGF-beta signaling via T beta RI. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
endothelial cell, hematopoiesis, serine, signal transduction, TGF-beta, threonine kinase receptor
in
EMBO Journal
volume
20
issue
7
pages
1663 - 1673
publisher
Oxford University Press
external identifiers
  • wos:000167981400018
  • scopus:17744397294
ISSN
1460-2075
DOI
10.1093/emboj/20.7.1663
language
English
LU publication?
yes
id
0fc387de-8c87-4d06-87c1-cb83172ed8ee (old id 1122299)
date added to LUP
2008-07-03 09:34:14
date last changed
2018-02-18 04:21:13
@article{0fc387de-8c87-4d06-87c1-cb83172ed8ee,
  abstract     = {Deletion of the transforming growth factor beta1 (TGF-beta1) gene in mice has previously suggested that it regulates both hematopoiesis and angiogenesis. To define the function of TGF-beta more precisely, we inactivated the TGF-beta type I receptor (T beta RI) gene by gene targeting. Mice lacking T beta RI die at midgestation, exhibiting severe defects in vascular development of the yolk sac and placenta, and an absence of circulating red blood cells. However, despite obvious anemia in the T beta RI-/- yolk sacs, clonogenic assays on yolk sac-derived hematopoietic precursors in vitro revealed that T beta RI-/- mice exhibit normal hematopoietic potential compared with wild-type and heterozygous siblings, Endothelial cells derived from T beta RI-deficient embryos show enhanced cell proliferation, improper migratory behavior and impaired fibronectin production in vitro, defects that are associated with the vascular defects seen in vivo. We thus demonstrate here that, while T beta RI is crucial for the function of TGF-beta during vascular development and can not be compensated for by the activin receptor-like kinase-1 (ALK-1), functional hematopoiesis and development of hematopoietic progenitors is not dependent on TGF-beta signaling via T beta RI.},
  author       = {Larsson, Jonas and Goumans, Marie-José and Jansson Sjöstrand, Lottie and van Rooijen, Marga A. and Ward, Dorien and Levéen, Per and Xu, Xiufeng and ten Dijke, Peter and Mummery, Christine L. and Karlsson, Stefan},
  issn         = {1460-2075},
  keyword      = {endothelial cell,hematopoiesis,serine,signal transduction,TGF-beta,threonine kinase receptor},
  language     = {eng},
  number       = {7},
  pages        = {1663--1673},
  publisher    = {Oxford University Press},
  series       = {EMBO Journal},
  title        = {Abnormal angiogenesis but intact hematopoietic potential in TGF-beta type I receptor-deficient mice},
  url          = {http://dx.doi.org/10.1093/emboj/20.7.1663},
  volume       = {20},
  year         = {2001},
}