Dumont D J, Fong G H, Puri M C, Gradwohl G, Alitalo K, Breitman M L
Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Dev Dyn. 1995 May;203(1):80-92. doi: 10.1002/aja.1002030109.
We report the detailed developmental expression profiles of three endothelial specific receptor tyrosine kinases (RTKs) flk-1, tek, tie, as well as vascular endothelial growth factor (VEGF), the flk-1 ligand. We also examined the expression of the other VEGF receptor, flt-1, during placental development. flk-1, tek, and tie transcripts were detected sequentially at one-half day intervals starting at E7.0, suggesting that each of these RTKs play a unique role during vascularization of the mouse embryo. All three RTKs were expressed in the extraembryonic and embryonic mesoderm in regions that eventually give rise to the vasculature. 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 virtually indistinguishable. An abundant amount of flt-1 transcripts was found in the spongiotrophoblast cells of the developing placenta from E8.0 onwards. This cellular compartment is located between the maternal and 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 expression displayed an expression profile both contiguous with that of flk-1, and also in tissues found some distance from the flk-1-expressing endothelium. These results suggest a possible dual role for VEGF which includes a chemotactic and/or a cellular maintenance role for VEGF during vascularization of the mouse embryo.
我们报告了三种内皮细胞特异性受体酪氨酸激酶（RTKs），即flk-1、tek、tie，以及flk-1配体血管内皮生长因子（VEGF）详细的发育表达谱。我们还检测了另一种VEGF受体flt-1在胎盘发育过程中的表达。从E7.0开始，每隔半天依次检测到flk-1、tek和tie的转录本，这表明这些RTKs在小鼠胚胎血管形成过程中各自发挥独特作用。所有这三种RTKs均在最终形成血管系统的胚外和胚胎中胚层中表达。除了tek和flk-1在羊膜中胚层表达外，从E8.5起，这些RTKs的表达几乎无法区分。从E8.0起，在发育中的胎盘的海绵滋养层细胞中发现了大量flt-1转录本。这个细胞区室位于胎盘的母体层和迷路层之间，这两层均表达VEGF。早在E7.0时，就在与flk-1阳性中胚层相邻的内胚层中检测到VEGF转录本，在发育后期，VEGF的表达谱既与flk-1的表达谱相邻，也存在于与表达flk-1的内皮细胞有一定距离处的组织中。这些结果表明VEGF可能具有双重作用，包括在小鼠胚胎血管形成过程中对VEGF的趋化作用和/或细胞维持作用。
