EXPRESSION OF THE FMS-LIKE TYROSINE KINASE-4 GENE BECOMES RESTRICTED TO LYMPHATIC ENDOTHELIUM DURING DEVELOPMENT

We have recently cloned the human fms-like tyrosine kinase 4 gene FLT4 , whose protein product is related to two vascular endothelial growth factor receptors FLT1 and KDR/FLK1, Here the expression of FLT4 has be en analyzed by in situ hybridization during mouse embryogenesis and in adult human tissues. The FLT4 mRNA signals first became detectable in the angioblasts of head mesenchyme, the cardinal vein, and extraembry onally in the allantois of 8.5 day postcoitus (p.c.) embryos. In 12.5- day p,c, embryos, the FLT4 signal decorated developing venous and pres umptive lymphatic endothelia, but arterial endothelia were negative. D uring later stages of development, FLTI mRNA became restricted to vasc ular plexuses devoid of red cells, representing developing lymphatic v essels. Only the lymphatic endothelia and some high endothelial venule s expressed FLT4 mRNA in adult human tissues. Increased expression occ urred in lymphatic sinuses in metastatic lymph nodes and in lymphangio ma, Our results suggest that FLT4 is a marker for lymphatic vessels an d some high endothelial venules in human adult tissues. They also supp ort the theory on the venous origin of lymphatic vessels.