Figure 7. Proximity to the stroma affects NPC fate.

(A,B) E11.5 Foxd1-Cre;Rosa-Wnt1; Rosa-YFP isolated MM were cultured for 2 days and subjected to in-situ hybridization for Wnt9b Wnt9b differentiation target gene C1qdc2 (A′) or renewal target gene Cited1 (B′) followed by IF stain for GFP (A″, B″). In A and B, the fluorescent image and a pseudo-colored version of the in-situ image were merged. Note that the differentiation target C1qdc2 is expressed immediately adjacent to the Wnt source while the renewal target is expressed at a distance from the source of the Wnt. Scale bars are 200uM. C: Model for Wnt/beta-catenin signaling in NPCs. Schematic representation of the embryonic kidney indicating the Wnt9b-expressing UB epithelium in red, the renewing NPCs that express Wnt9b renewal targets in light blue, the differentiating NPCs or pre-tubular aggregates (PTAs) that express Wnt9b differentiation targets in dark blue, the cortical stromal cells in green and the medullary stromal cells in orange. Wnt9b ligand is produced by the UB and secreted to the surrounding MM where it stimulates a low/baseline level of beta-catenin activity, which promotes renewal. High levels of beta-catenin activity which promote differentiation are a result of unknown beta-catenin amplifying signal(s), perhaps emanating from the medullary stroma and/or higher active Wnt ligand in the medullary NPCs.