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 are specifically expressed in developing vascular endothelial cells. To study the functions of Tie-1 and Tie-2 during vascular endothelial cell growth and differentiation in vivo, targeted mutations of the genes in mice were introduced by homologous recombination. Embryos deficient in Tie-1 failed to establish structural integrity of vascular endothelial cells, resulting in oedema and subsequently localized haemorrhage. However, analyses of embryos deficient in Tie-2 showed that it is important in angiogenesis, particularly for vascular network formation in endothelial cells. This result contrasts with previous reports on Tie-2 function in vasculogenesis and/or endothelial cell survival. Our in vivo analyses indicate that the structurally related receptor tyrosine kinases Tie-1 and Tie-2 have important but distinct roles in the formation of blood vessels.
Sato
T N
TN
Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110, USA.
Tozawa
Y
Y
Deutsch
U
U
Wolburg-Buchholz
K
K
Fujiwara
Y
Y
Gendron-Maguire
M
M
Gridley
T
T
Wolburg
H
H
Risau
W
W
Qin
Y
Y
D000818:Animals; D001483:Base Sequence; D001808:Blood Vessels / Q000196:embryology* / Q000254:growth & development; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D017931:DNA Primers; D004487:Edema / Q000196:embryology; D004730:Endothelium, Vascular / Q000166:cytology / Q000196:embryology*; D006470:Hemorrhage / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010641:Phenotype; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D042810:Receptor, TIE-1; D042787:Receptor, TIE-2; D042764:Receptors, TIE
D017931:DNA Primers; D020794:Receptor Protein-Tyrosine Kinases; D042810:Receptor, TIE-1; D042787:Receptor, TIE-2; D042764:Receptors, TIE