DEFECTS OF UROGENITAL DEVELOPMENT IN MICE LACKING EMX2

The homeobox gene Emx2 is a mouse homologue of a Drosophila head gap g ene empty spiracles (ems) and is essential for the development of dors al telencephalon (Yoshida, M., Suda, Y., Matsuo, I., Miyamoto, N., Tak eda, N., Kuratani, S. and Aizawa, S. (1997) Development 124, 101-111), At the same time, Emx2 is expressed in the epithelial components of t he developing urogenital system and, in Emx2 mutant mice, the kidneys, ureters, gonads and genital tracts were completely missing, Pax-2 and c-ret expressions in the Wolffian duct and WT-1 and GDNF expressions in the metanephric blastema were initially normal in the mutant, The u reteric bud grew and invaded the metanephric mesenchyme where Pax-2 ex pression was normally induced, Subsequently, however, Pax-2, c-ret and Lim1 expressions in the ureteric bud and GDNF expression in the mesen chyme were greatly reduced, Wnt-4 expression was never found in the me senchyme, The tip of the ureteric bud never dilated and branching of t he bud did not occur, Neither pretubular cell aggregates nor epithelia lization were found in the mesenchyme, Instead the ureteric bud soon d egenerated and apoptotic figures were prominent in mesenchymal cells, In explant culture, the mutant ureteric bud did not induce the epithel ial transformation of the wild-type mesenchyme, and branching of the m utant ureteric bud was not induced by wild-type mesenchyme, In contras t, defects were not apparent in the mutant mesenchyme by co-culture wi th mild-type ureteric bud or spinal cord, These results suggest that, in metanephrogenesis, Emx2 is essential for the ureteric bud functions subsequent to Pax-2 induction in the metanephric mesenchyme, Degenera tion of the Wolffian duct and mesonephric tubules was also abnormally accelerated without the formation of the Mullterian duct.