THE MOUSE TIE RECEPTOR TYROSINE KINASE GENE - EXPRESSION DURING EMBRYONIC ANGIOGENESIS

Angiogenesis, the process by which new blood vessels are formed, is es sential in reproduction, development, wound repair and oncogenesis. En dothelial receptor tyrosine kinases are Likely to play key roles in th e intercellular signalling controlling angiogenesis. We have here anal ysed the expression of the endothelial receptor tyrosine kinase tie du ring the earliest stages of vascular development. The mouse tie cDNA w as isolated and sequenced and the exon structure of the coding region was determined. The part of the tie gene encoding the extracellular do main was found to be organized in exons specifying the characteristic domains of the Tie polypeptide. Early postimplantation mouse tissues w ere analysed for tie expression by in situ hybridization. No tie mRNA was detected in 7.5 day mouse embryos. In 8.5 day embryos, tie express ion was observed in differentiating angioblasts of the head mesenchyme , in the splanchnopleure and dorsal aorta as well as in migrating endo thelial cells of the developing heart. A weak tie signal was also obta ined from angioblasts in the blood islands of the yolk sac. Furthermor e, tie mRNA was prominent in the endocardium of the embryo and in the endothelial cells forming the lung vasculature. Expression of tie pers isted in the lung capillaries of adult mice, but was decreased in the endocardium. These results suggest that the tie receptor tyrosine kina se is involved in angiogenesis and/or maintenance of endothelial cell functions.