Fig. 1. Expression of Fgf8 in the developing kidney and phenotype of Fgf8-MM-KO kidneys at E18.5. (A) Schematic diagrams illustrating the early stages of nephron formation (nephrogenesis; left) and the mature nephron (right). During development, nephron and stroma progenitors are localized in the peripheral zone near the outermost edge of the kidney primordium, whereas the branching collecting duct system is localized to the central region of the rudiment. Nascent nephrons form adjacent to collecting duct tips and develop into S-shaped bodies that differentiate into the various cell types of the nephron. During nephron maturation, invasion of the podocyte layer by endothelial cells (not illustrated) leads ultimately to the formation of a capillary tuft that becomes enveloped by podocytes. Together with the surrounding squamous epithelium of Bowman's capsule, they comprise the renal corpuscle portion of the mature nephron. The tubular portion of the nephron consists of three distinct segments: the proximal tubule, the loop of Henle, and the distal tubule, which connects to the collecting duct system. (B-E) Whole mounts of E11.5-E12.5 mouse kidney primordia (B-D), and cryo-sections of E16.5 kidneys (E), processed for in situ hybridization to localize expression of Fgf8. At higher magnification, Fgf8 expression is detected in (E',E'') nascent nephrons and (E''') the tubule progenitor cells within S-shaped bodies. (F) Analysis of lacZ expression (blue staining) in sections through E12.5 kidneys from embryos carrying the Pax3-cre transgene and the R26R reporter allele. Note that only ureteric bud-derived collecting duct epithelia do not express lacZ (pink staining). (G) Comparison of intact normal and Fgf8-MM-KO kidneys at E18.5. (H,I) Immunofluorescence assays in vibratome sections through E18.5 normal and Fgf8-MM-KO kidneys for PAX2 (green), which normally labels nephron progenitors in the cortex as well as collecting ducts present in both cortex and medulla, and smooth muscle actin (SMA, red), which normally labels the stroma in the medulla, the vasculature in the cortex, and the ureter. (J-K'') Low (J,K) and high (J',K',K'') power views of cryo-sections, showing expression of Wnt4 and Fgfr1 in E16.5 kidneys. Wnt4 and Fgfr1 transcripts are detected in nascent nephrons. In addition, Fgfr1 transcripts are detected in the peripheral zone and throughout the S-shaped bodies. BC, Bowman's capsule progenitors; CD, collecting duct progenitors; Co, cortex; Me(I), inner medullary region; Me(O), outer medullary region; NN, nascent nephron; Po, podocyte progenitors; PZ, peripheral zone; Tu, tubule progenitors; UB, ureteric bud; Ur, ureter.