Induced repatterning of type XVIII collagen expression in ureter bud from kidney to lung type: association with sonic hedgehog and ectopic surfactantprotein C

Epithelial-mesenchymal tissue interactions regulate the formation of signal ing centers that play a role in the coordination of organogenesis, but it i s not clear how their activity leads to differences in organogenesis, We re port that type XVIII collagen, which contains both a frizzled and an endost atin domain, is expressed throughout the respective epithelial bud at the i nitiation of lung and kidney organogenesis, It becomes localized to the epi thelial tips in the lung during the early stages of epithelial branching, w hile its expression in the kidney is confined to the epithelial stalk regio n and is lost from the nearly formed ureter tips, thus displaying the rever se pattern to that in the lung. In recombinants, between ureter bud and lun g mesenchyme, type XVIII collagen expression pattern in the ureter bud shif ts from the kidney to the lung type, accompanied by a shift in sonic hedgeh og expression in the epithelium. The lung mesenchyme is also sufficient to induce ectopic lung surfactant protein C expression in the ureter bud. More over, the shift in type XVIII collagen expression is associated with change s in ureter development, thus resembling aspects of early lung type epigene sis in the recombinants, Respecification of collagen is necessary for the r epatterning process, as type XVIII collagen antibody blocking had no effect on ureter development in the intact kidney, whereas it reduced the number of epithelial tips in the lung and completely blocked ureter development wi th lung mesenchyme, Type XVIII collagen antibody blocking also led to a not able reduction in the expression of Wnt2, which is expressed in the lung me senchyme but not in that of the kidney, suggesting a regulatory interaction between this collagen and Wnt2, Respecification also occurred in a chimeri c organ containing the ureter bud and both kidney and lung mesenchymes, ind icating that the epithelial tips can integrate the morphogenetic signals in dependently. A glial cell line-derived neurotrophic factor signal induces l oss of type XVIII collagen from the ureter tips and renders the ureter bud competent for repatterning by lung mesenchyme-derived signals, Our data sug gest that differential organ morphogenesis is regulated by an intra-organ p atterning process that involves coordination between inductive signals and matrix molecules, such as type XVIII collagen.