Sp. Mah et al., Kidney development in cadherin-6 mutants: Delayed mesenchyme-to-epithelialconversion and loss of nephrons, DEVELOP BIO, 223(1), 2000, pp. 38-53
During nephrogenesis, dynamic changes in the expression of cell adhesion mo
lecules are evident as epithelial structures differentiate from the induced
mesenchyme. The cadherins are thought to play an important role in the met
anephric mesenchyme, when cells aggregate to form the renal vesicle, a pola
rized epithelial structure which eventually fuses with the ureteric bud to
generate a continuous nascent nephron. We have generated and analyzed mice
with a targeted mutation in the gene encoding cadherin-6 (Cad-6), a type II
cadherin expressed during early stages of nephrogenesis. These mice are vi
able and fertile, and they complete both early and late aspects of nephroge
nesis. However, upon closer examination in vitro and in vivo, a fraction of
the induced metanephric mesenchyme in Cad-6 mutant kidneys fails to form a
fully polarized epithelium on schedule. Moreover, a significant number of
the renal vesicles in Cad-6 mutant kidneys apparently fail to fuse to the u
reteric bud. These alterations in epithelialization and fusion apparently l
end to a loss of nephrons in the adult. These studies support the idea that
cadherins play an essential role in the formation of epithelial structures
and underscore the importance of timing in orchestrating the morphogenesis
of complex epithelial tissues. (C) 2000 Academic Press.