Induction of ureter branching as a response to Wnt-2b signaling during early kidney organogenesis

Epithellial-mesenchymal tissue interactions play a central role in vertebra te organogenesis, but the molecular mediators and mechanisms of these morph ogenetic interactions are still not well characterized. We report here on t he expression pattern of Wnt-2b during mouse organogenesis and on tests of its function in epithelial-mesenchymal interactions during kidney developme nt. Wnt-2b is expressed in numerous developing organs in the mouse embryo, including the kidney, lung, salivary gland, gut, pancreas, adrenal gland, a nd genital tubercle. Additional sites of expression include the branchial a rches and craniofacial placodes such as the eye and ear. The data suggest t hat the expression of Wnt-2b is associated with organs regulated by epithel ial-mesenchymal interactions. It is typically localized in the capsular epi thelium or peripheral mesenchymal cells of organ rudiments, e.g., the perin ephric mesenchymal cells in the region of the presumptive renal stroma in t he developing kidney at E11.5. Functional studies of the kidney demonstrate that cells expressing Wnt-2b are not capable of inducing tubule formation but instead stimulate ureter development. Incubation of isolated ureteric b uds on such cells supports bud growth and branching. In addition, recombina tion of Wnt-2b-pretreated ureteric bud tissue with isolated nephrogenic mes enchyme results in a recovery of organogenesis and the expression of epithe lial genes within the reconstituted organ explant. Lithium, a known activat or of Wnt signaling (Hedgepeth et al. [1997] Dev Biol 185:82-91), is also s ufficient to promote ureter branching in the reconstituted kidney in a comp arable manner to Wnt-2b signaling, whereas Wnt-4, which induces tubules, ne ither supports the growth of a ureteric bud nor leads to reconstitution of the ureteric bud with the kidney mesenchyme. We conclude that Wnt-2b may ac t in the mouse kidney as an early mesenchymal signal controlling morphogene sis of epithelial tissue, and that the Wnt pathway may regulate ureter bran ching directly. In addition, Wnt signals in the kidney differ qualitatively and are specific to either the epithelial ureteric bud or the kidney mesen chyme. (C) 2001 Wiley-Liss, Inc.