Defects of urogenital development in mice lacking Emx2.
The homeobox gene Emx2 is a mouse homologue of a Drosophila head gap gene empty spiracles (ems) and is essential for the development of dorsal telencephalon (Yoshida, M., Suda, Y., Matsuo, I., Miyamoto, N., Takeda, N., Kuratani, S. and Aizawa, S. (1997) Development 124, 101-111). At the same time, Emx2 is expressed in the epithelial components of the 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 ureteric bud grew and invaded the metanephric mesenchyme where Pax-2 expression was normally induced. Subsequently, however, Pax-2, c-ret and Lim1 expressions in the ureteric bud and GDNF expression in the mesenchyme were greatly reduced. Wnt-4 expression was never found in the mesenchyme. The tip of the ureteric bud never dilated and branching of the bud did not occur. Neither pretubular cell aggregates nor epithelialization were found in the mesenchyme. Instead the ureteric bud soon degenerated and apoptotic figures were prominent in mesenchymal cells. In explant culture, the mutant ureteric bud did not induce the epithelial transformation of the wild-type mesenchyme, and branching of the mutant ureteric bud was not induced by wild-type mesenchyme. In contrast, defects were not apparent in the mutant mesenchyme by co-culture with wild-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. Degeneration of the Wolffian duct and mesonephric tubules was also abnormally accelerated without the formation of the Mullerian duct.
Miyamoto
N
N
Department of Morphogenesis, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University School of Medicine, Honjo, Japan.
Yoshida
M
M
Kuratani
S
S
Matsuo
I
I
Aizawa
S
S
D000818:Animals; D000013:Congenital Abnormalities / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004330:Drosophila; D005314:Embryonic and Fetal Development; D004848:Epithelium / Q000002:abnormalities / Q000196:embryology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D016162:Genes, Wilms Tumor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006066:Gonads / Q000002:abnormalities; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006720:Homozygote; D007668:Kidney / Q000002:abnormalities; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009414:Nerve Growth Factors; D009687:Nuclear Proteins; D009924:Organ Culture Techniques; D016133:Polymerase Chain Reaction; D012732:Sex Determination Analysis; D051876:Sex-Determining Region Y Protein; D013687:Telencephalon / Q000196:embryology; D014157:Transcription Factors / Q000096:biosynthesis; D014513:Ureter / Q000002:abnormalities; D014564:Urogenital Abnormalities; D014566:Urogenital System / Q000196:embryology*; D025721:WT1 Proteins; D000099260:Empty Spiracles Homeobox Proteins
D004268:DNA-Binding Proteins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018398:Homeodomain Proteins; D009414:Nerve Growth Factors; D009687:Nuclear Proteins; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors; D025721:WT1 Proteins; D000099260:Empty Spiracles Homeobox Proteins; C495040:Gdnf protein, mouse