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Fig. 4. Dynamic changes in Grem1 and
Bmp4 expression during initiation of metanephric kidney
development in mouse. (A-D) Bmp4 distribution during
initiation of metanephric kidney development. (A,B) GFP reveals the morphology
of the nascent ureteric bud at E11.0 (40-42 somites; A) and after the first
epithelial branching (E11.5, 48-50 somites; B). Asterisks in B indicate the
tips of the ureter branches. (C,D) The Bmp4 transcript distribution
was determined using a lacZ reporter gene inserted into the
endogenous Bmp4 transcription unit (Bmp4:lacZ) in
heterozygous embryos (Kulessa and Hogan,
2002), as detection by whole mount in situ hybridisation is not
reliable. (C) At E11.0, Bmp4:lacZ is expressed by the mesenchyme
surrounding the Wolffian duct (arrow) and ureteric bud (see also G). The
dotted circle indicates the position of the ureteric bud (compare with A). (D)
By E11.5, the Bmp4:lacZ expression is retained in the mesenchyme
surrounding the Wolffian duct (arrow), while the metanephric mesenchyme is
largely devoid of Bmp4. The dotted line indicates the position of the
first branch (compare with B). (E,F) Grem1 expression
in the mesenchyme. (E) At E11.0, Grem1 expression is highest in the
mesenchyme around the ureteric bud (indicated by a dotted circle). (F)
Subsequently (E11.5), Grem1 is expressed in the mesenchyme around the
tips of first ureteric epithelial branch (indicated by dotted oval).
(G,H) Detection of Bmp4 and Grem1 transcripts
on transverse sections by in situ hybridisation. Sections are oriented with
dorsal to the top. Note that the epithelium (indicated by a dotted line)
expresses neither Bmp4 (G) nor Grem1 (H). (G) There is
abundant Bmp4 expression in the mesenchyme around the caudal Wolffian
duct and ureteric epithelium in agreement with the Bmp4:lacZ
distribution shown in C. (H) At E10.75 (38 somites), Grem1 is also
expressed in the mesenchyme around the caudal Wolffian duct and ureteric
epithelium in agreement with the whole mount in situ hybridisation shown in E.
Note that Bmp4 and Grem1 are also expressed by the
mesenchyme around the hindgut. Hg, hindgut; mm,: metanephric mesenchyme; wd,
Wolffian duct.