DISTINCT ROLES OF THE RECEPTOR TYROSINE KINASES TIE-1 AND TIE-2 IN BLOOD-VESSEL FORMATION

TIE-1 and Tie-2 define a new class of receptor tyrosine kinases that a re specifically expressed in developing vascular endothelial cells. To study the functions of Tie-1 and Tie-2 during vascular endothelial ce ll growth and differentiation in vivo, targeted mutations of the genes in mice were introduced by homologous recombination. Embryos deficien t in Tie-1 failed to establish structural integrity of vascular endoth elial cells, resulting in oedema and subsequently localized haemorrhag e. However, analyses of embryos deficient in Tie-2 showed that it is i mportant in angiogenesis, particularly for vascular network formation in endothelial cells. This result contrasts with previous reports on T ie-2 function in vasculogenesis and/or endothelial cen survival. Our i n vivo analyses indicate that the structurally related receptor tyrosi ne kinases Tie-1 and Tie-2 have important hut distinct roles in the fo rmation of blood vessels.