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

Deletion of the transforming growth factor beta1 (TGF-beta1) gene in mice h as previously suggested that it regulates both hematopoiesis and angiogenes is. To define the function of TGF-beta more precisely, we inactivated the T GF-beta type I receptor (T beta RI) gene by gene targeting. Mice lacking T beta RI die at midgestation, exhibiting severe defects in vascular developm ent of the yolk sac and placenta, and an absence of circulating red blood c ells. However, despite obvious anemia in the T beta RI-/- yolk sacs, clonog enic 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 ass ociated with the vascular defects seen in vivo. We thus demonstrate here th at, 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 ki nase-1 (ALK-1), functional hematopoiesis and development of hematopoietic p rogenitors is not dependent on TGF-beta signaling via T beta RI.