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

Deletion of the transforming growth factor s1 (TGF-s1) gene in mice has previously suggested that it regulates both hematopoiesis and angiogenesis. To define the function of TGF-s more precisely, we inactivated the TGF-s type I receptor (TsRI) gene by gene targeting. Mice lacking TsRI 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 TsRI super(-/-) yolk sacs, clonogenic assays on yolk sac-derived hematopoietic precursors in vitro revealed that TsRI super(-/-) mice exhibit normal hematopoietic potential compared with wild-type and heterozygous siblings. Endothelial cells derived from TsRI-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 TsRI is crucial for the function of TGF-s 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-s signaling via TsRI.