VASCULARIZATION OF THE MOUSE EMBRYO - A STUDY OF FLK-1, TEK, TIE, ANDVASCULAR ENDOTHELIAL GROWTH-FACTOR EXPRESSION DURING DEVELOPMENT

We report the detailed developmental expression profiles of three endo thelial specific receptor tyrosine kinases (RTKs) flk-1, tek, tie, as well as vascular endothelial growth factor (VEGF), the flk-1 ligand. W e also examined the expression of the other VEGF receptor, flt-1, duri ng placental development. flk-1, tek, and tie transcripts were detecte d sequentially at one-half day intervals starting at E7.0, suggesting that each of these RTKs play a unique role during vascularization of t he mouse embryo. All three RTKs were expressed in the extraembryonic a nd embryonic mesoderm in regions that eventually give rise to the vasc ulature. Except for the expression of tek and flk-1 in the mesoderm of the amnion, the expression of these RTKs from E8.5 onwards was virtua lly indistinguishable. An abundant amount of flt-1 transcripts was fou nd in the spongiotrophoblast cells of the developing placenta from E8. 0 onwards. This cellular compartment is located between the maternal a nd labyrinthine layers of the placenta, which both express VEGF. VEGF transcripts were detected as early as E7.0 in the endoderm juxtaposed to the flk-1 positive mesoderm, and later in development VEGF expressi on displayed an expression profile both contiguous with that of flk-1, and also in tissues found some distance from the flk-1-expressing end othelium. These results suggest a possible dual role for VEGF which in cludes a chemotactic and/or a cellular maintenance role for VEGF durin g vascularization of the mouse embryo. (C) 1995 Wiley-Liss, Inc.