Michael Lydia, Sweeney Derina E, Davies Jamie A
Centre for Integrative Physiology, Edinburgh University College of Medicine, Edinburgh, UK.
J Anat. 2007 Jan;210(1):89-97. doi: 10.1111/j.1469-7580.2006.00670.x.
The urine collecting duct system of the metanephric kidney develops by growth and branching morphogenesis of an unbranched progenitor tubule, the ureteric bud. Bud branching is mainly dichotomous and new branches form from existing branch tips, which are also the main sites of cell proliferation in the system. This behaviour, and the fact that some genes (e.g. Wnt11, Sox9) are expressed only in tips, suggests that tip cells are in a specific state of differentiation. In this report, we show that the lectin Dolichos biflorus agglutinin (DBA), hitherto regarded and used as a general marker of developing renal collecting ducts, binds to most of the duct system but does not bind to the very tips of growing branches. The zone avoided by DBA corresponds to the zone that expresses Wnt11, and the zone that shows enhanced cell proliferation. If branching of the ureteric bud of cultured embryonic kidneys is inhibited in organ culture, by blocking the kidney's endogenous glial cell-derived neurothrophic factor (GDNF)-based branch-promoting signals, the DBA-binding zone extends to the very end of the tip but is lost from there when branching is re-activated. Similarly, if excess GDNF is provided to growing kidneys, the DBA-free zone expands. DBA-staining status therefore appears to be a sensitive indicator of the morphogenetic activity of the collecting duct system.
后肾的集合管系统由一个未分支的祖小管——输尿管芽通过生长和分支形态发生发育而来。芽的分支主要是二分的,新分支从现有的分支末端形成,这些末端也是该系统中细胞增殖的主要部位。这种行为,以及一些基因(如Wnt11、Sox9)仅在末端表达这一事实,表明末端细胞处于特定的分化状态。在本报告中,我们表明,凝集素双花扁豆凝集素(DBA),迄今为止一直被视为并用作发育中肾集合管的通用标记物,可与大部分集合管系统结合,但不与正在生长的分支的最末端结合。DBA避开的区域对应于表达Wnt11的区域,以及显示细胞增殖增强的区域。如果在器官培养中通过阻断肾脏内源性基于胶质细胞源性神经营养因子(GDNF)的分支促进信号来抑制培养的胚胎肾脏输尿管芽的分支,DBA结合区域会延伸到末端的最末端,但当分支重新激活时,该区域会从那里消失。同样,如果向正在生长的肾脏提供过量的GDNF,无DBA区域会扩大。因此,DBA染色状态似乎是集合管系统形态发生活性的一个敏感指标。