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

Larsson, JonasLund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine (author)

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.

Goumans, Marie-José (author)
Jansson Sjöstrand, LottieLund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)molm-lja (author)
van Rooijen, Marga A. (author)
Ward, Dorien (author)
Levéen, PerLund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)molm-ple (author)
Xu, Xiufeng (author)
ten Dijke, Peter (author)
Mummery, Christine L. (author)
Karlsson, StefanLund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)molm-ska (author)
Avdelningen för molekylärmedicin och genterapiInstitutionen för laboratoriemedicin (creator_code:org_t)

By the author/editor: Larsson, Jonas; Goumans, Marie-J ...; Jansson Sjöstran ...; van Rooijen, Mar ...; Ward, Dorien; Levéen, Per; show more...; Xu, Xiufeng; ten Dijke, Peter; Mummery, Christi ...; Karlsson, Stefan; show less...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

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