Fig. 6. Disruption of metanephric kidney morphogenesis. (A-C) Distribution of Grem1 transcripts during kidney morphogenesis. (A) Grem1 expression in the Wolffian duct and mesonephric tubules during E10.0. (B) Distribution of Grem1 transcripts during initiation of metanephric development (E11.0). The distribution of lacZ transcripts in a Gre^ORF heterozygous embryonic kidney is shown. Note expression by both posterior Wolffian duct and metanephric mesenchyme. The broken line indicates the approximate position corresponding to the section shown in C. (C) In situ analysis on section reveals Grem1 expression locally in the metanephric mesenchyme surrounding the ureter tips. (D) Growth of the ureter and invasion of the metanephric mesenchyme in wild-type embryos occurs by E11.25. This growth and invasion results in upregulation of Pax2 expression in the induced mesenchyme in wild type, while it remains low in mutant mesenchyme. (E) In contrast to the wild type, Pax2 expression is lost from mutant mesenchyme by E12.5, while it remains similar to the wild type in the Wolffian duct. (F) In contrast to the wild type, Bmp2 fails to be expressed by the nephrogenic regions of mutant embryos. (G) In wild-type embryos, Bmp7 expression is induced to high levels within the condensing mesenchyme. This induction is completely disrupted in Grem1-deficient embryos. In D-G, only the metanephric region is shown. cm, condensing metanephric mesenchyme; gr, genital ridge; mm, metanephric mesenchyme; ub, ureteric bud; ur, ureter; wd, Wolffian duct.