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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.
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