Glial cell line-derived neurotrophic factor
positive regulation of branching involved in ureteric bud morphogenesis
The lectin Dolichos biflorus agglutinin is a sensitive indicator of branching morphogenetic activity in the developing mouse metanephric collecting duct system.
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.