Regulation of metanephric kidney development by growth/differentiation factor 11.
Growth/differentiation factor 11 (Gdf11) is a transforming growth factor beta family member previously shown to control anterior/posterior patterning of the axial skeleton. We now report that Gdf11 also regulates kidney organogenesis. Mice carrying a targeted deletion of Gdf11 possess a spectrum of renal abnormalities with the majority of mutant animals lacking both kidneys. Histological analysis revealed a failure in ureteric bud formation at the initial stage of metanephric development in most Gdf11 mutant embryos examined. The metanephric mesenchyme of mutant embryos lacking a ureteric bud was found to be defective in the expression of glial cell line-derived neurotrophic factor (Gdnf), a gene known to direct ureteric bud outgrowth. The addition of Gdnf protein to urogenital tracts taken from Gdf11 null embryos induced ectopic ureteric bud formation along the Wolffian duct. Our studies suggest that Gdf11 may be important in directing the initial outgrowth of the ureteric bud from the Wolffian duct by controlling the expression of Gdnf in the metanephric mesenchyme.
Esquela
Aurora F
AF
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. fe@jhmi.edu
Lee
Se-Jin
SJ
D030301:Activin Receptors, Type II / Q000235:genetics; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005819:Genetic Markers; D051100:Glial Cell Line-Derived Neurotrophic Factor; D055412:Growth Differentiation Factors; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000002:abnormalities* / Q000473:pathology / Q000502:physiology; D008297:Male; D008648:Mesoderm; D051379:Mice; D008817:Mice, Mutant Strains; D009414:Nerve Growth Factors / Q000235:genetics; D009924:Organ Culture Techniques; D014513:Ureter / Q000196:embryology
D019485:Bone Morphogenetic Proteins; C119153:Gdf11 protein, mouse; C495040:Gdnf protein, mouse; D005819:Genetic Markers; D051100:Glial Cell Line-Derived Neurotrophic Factor; D055412:Growth Differentiation Factors; D009414:Nerve Growth Factors; D030301:Activin Receptors, Type II; C425584:activin receptor type II-B