Zhong T P, Childs S, Leu J P, Fishman M C
Cardiovascular Research Center, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Charlestown 02129, USA.
Nature. 2001 Nov 8;414(6860):216-20. doi: 10.1038/35102599.
Arteries and veins are morphologically, functionally and molecularly very different, but how this distinction is established during vasculogenesis is unknown. Here we show, by lineage tracking in zebrafish embryos, that angioblast precursors for the trunk artery and vein are spatially mixed in the lateral posterior mesoderm. Progeny of each angioblast, however, are restricted to one of the vessels. This arterial-venous decision is guided by gridlock (grl), an artery-restricted gene that is expressed in the lateral posterior mesoderm. Graded reduction of grl expression, by mutation or morpholino antisense, progressively ablates regions of the artery, and expands contiguous regions of the vein, preceded by an increase in expression of the venous marker EphB4 receptor (ephb4) and diminution of expression of the arterial marker ephrin-B2 (efnb2). grl is downstream of notch, and interference with notch signalling, by blocking Su(H), similarly reduces the artery and increases the vein. Thus, a notch-grl pathway controls assembly of the first embryonic artery, apparently by adjudicating an arterial versus venous cell fate decision.
动脉和静脉在形态、功能和分子层面上都有很大差异，但在血管生成过程中这种差异是如何形成的尚不清楚。在此，我们通过对斑马鱼胚胎进行谱系追踪发现，躯干动脉和静脉的成血管细胞前体在侧后中胚层中是空间混合的。然而，每个成血管细胞的后代都被限制在其中一条血管中。这种动静脉分化的决定是由gridlock（grl）基因引导的，该基因是一种在侧后中胚层中表达的动脉特异性基因。通过突变或吗啉代反义技术使grl表达水平逐步降低，会逐渐消融动脉区域，并扩展相邻的静脉区域，在此之前静脉标记物EphB4受体（ephb4）的表达会增加，而动脉标记物ephrin-B2（efnb2）的表达会减少。grl位于Notch信号通路的下游，通过阻断Su(H)干扰Notch信号传导，同样会减少动脉并增加静脉。因此，Notch-grl信号通路显然是通过决定动脉和静脉细胞命运的分化来控制第一条胚胎动脉的形成。
