Model of tubule interconnection patterned by reciprocal inhibition of Wnt signaling pathways. (A-C) fzd9b expression patterns cell proliferation and cell polarization in new nephrons. (A) At early stages of new nephron formation, fzd9b (green) is uniformly expressed in non-proliferating cell aggregates. (B) Early fzd9b expression (green) establishes a persistent non-proliferating cell state (red; EdU) in basal cells destined to invade the distal tubule. fzd9b simultaneously establishes apical constriction and orients basal protrusions in new nephron cells. (C) A mutation in fzd9b relieves the block in canonical Wnt-dependent basal cell proliferation, disrupts apical constriction, resulting in an enlarged lumen, and misorients basal protrusions to the lateral edges of the new nephron basal surface. (D-F) Reciprocal inhibition of canonical and non-canonical Wnt signaling component expression. (D) As new nephron formation progresses, fzd9b expression becomes excluded from the domain closest to the distal tubule, which is a domain of high canonical Wnt target gene expression, including wnt4. (E) Mutation in wnt4 permits strong uniform expression of fzd9b in new nephrons. wnt4 mutant cells remain rounded and non-polarized. (F) Mutation in fzd9b expands the expression domain of wnt4 and other canonical Wnt target genes in new nephrons.
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