QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 30 May 2007
doi: 10.1242/dev.006155

This Article Summary Full Text Full Text (PDF) Supplementary Material Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Park, J.-S. Articles by McMahon, A. P. Search for Related Content PubMed PubMed Citation Articles by Park, J.-S. Articles by McMahon, A. P. Social Bookmarking                         What's this?

Wnt/ß-catenin signaling regulates nephron induction during mouse kidney development

Joo-Seop Park^*, M. Todd Valerius^* and Andrew P. McMahon

Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.

View larger version (74K): [in this window] [in a new window]   Fig. 1. Removal of ß-catenin in renal vesicle progenitor cells causes reduced nephron formation in mice. (A) P1 kidneys from wild-type (left) and ß-catenin LOF mutant (right). White arrowheads point to the adrenal glands. (B-G) Histology of kidneys from LOF mutants of ß-catenin and proper controls at P1 (B-E) and at E13.5 (F,G). Six2TGC kidneys are slightly smaller than wild type. Scale bars: 0.5 mm in B-E, 0.1 mm in F,G. CD, collecting duct; NZ, nephrogenic zone; PA, pre-tubular aggregate; SB, S-shaped body.

View larger version (72K): [in this window] [in a new window]   Fig. 2. Removal of ß-catenin in renal vesicle progenitor cells in mice results in reduced tubulogenesis and branching. (A,B) Whole-mount in situ hybridization of HoxB7 (a marker for ureter) and (C-J) mesenchymal induction markers (Fgf8, Wnt4, Pax8 and Lhx1) on E12.5 embryonic kidneys from control (A,C,E,G,I) and LOF mutants of ß-catenin (B,D,F,H,J). Black arrowheads point to expression of mesenchymal induction markers in ß-catenin LOF mutants.

View larger version (66K): [in this window] [in a new window]   Fig. 3. Kidneys from GOF mutants of ß-catenin show ectopic expression of early tubule markers and reduced branching in mice. (A,B) Histology of kidneys from wild type and GOF mutants of ß-catenin at E13.5. Active nephrogenesis occurs in the cortex of wild-type kidneys (A), but neither S-shaped body nor nephron is formed in GOF mutants of ß-catenin (B). (C,D) Whole-mount in situ hybridization of HoxB7 and (E-L) the mesenchymal induction markers (Fgf8, Wnt4, Pax8 and Lhx1) on E12.5 embryonic kidneys from wild type (C,E,G,I,K) and GOF mutants of ß-catenin (D,F,H,J,L). White arrowheads indicate ectopic expression of mesenchymal induction markers dorsal to the ureteric epithelium. CD, collecting duct; NZ, nephrogenic zone; PA, pre-tubular aggregate; SB, S-shaped body.

View larger version (35K): [in this window] [in a new window]   Fig. 4. Activated Wnt/ß-catenin signaling in renal vesicle progenitor cells blocks the mesenchymal-to-epithelial transition in mice. (A-H) Analysis of epithelial formation by induced renal vesicle progenitors. (A,B) DBA-negative and (C,D) E-cadherin-positive cells represent epithelial tubules originated from renal vesicles. (E,F) ß-galactosidase (cyan) labels Six2TGC-expressing cells and their descendants. In wild-type embryos (G), most cells in this population express ß-galactosidase. However, in GOF mutants of ß-catenin (H), E-cadherin expression does not overlap with ß-galactosidase expression, indicating that Six2TGC-mediated activation of Wnt/ß-catenin pathway blocks epithelialization. Yellow arrowheads indicate E-cadherin-negative clusters of cells that originate from the Six2TGC-expressing cell population. White arrowheads indicate epithelial structures in adrenal gland.

View larger version (70K): [in this window] [in a new window]   Fig. 5. Metanephric mesenchyme explants from GOF mutants of ß-catenin express mesenchymal induction markers in mice. Metanephric mesenchyme explants dissected from E11.5 control (E-H) or ß-catenin GOF mutants (I-L) were tested for expression of mesenchymal induction markers. Whole kidney explants from control embryos (A-D) were used as positive control. MM, metanephric mesenchyme.

View larger version (105K): [in this window] [in a new window]   Fig. 6. Activated Wnt/ß-catenin signaling in renal vesicle progenitor cells in mice is sufficient to induce mesenchymal induction markers in the absence of Wnt9b. (A-P) Whole-mount in situ hybridization at E12.5. (A,E,I,M) HoxB7 and (B-D,F-H,J-L,N-P) the mesenchymal induction markers (Fgf8, Wnt4 and Lhx1) on E12.5 embryonic kidneys. The mesenchymal induction markers are not detected in kidneys from Wnt9b mutants (F,G,H) and ectopically expressed when Wnt/ß-catenin pathway is activated by Six2TGC (J,K,L). Six2TGC-mediated activation of Wnt/ß-catenin pathway also causes ectopic expression of the mesenchymal induction markers in Wnt9b mutants (N,O,P).

View larger version (106K): [in this window] [in a new window]   Fig. 7. Activated Wnt/ß-catenin signaling in renal vesicle progenitor cells in mice is sufficient to induce mesenchymal induction markers in the absence of Wnt4. (A-P) Whole-mount in situ hybridization at E12.5. (A,E,I,M) Whole-mount in situ hybridization of HoxB7 and (B-D,F-H,J-L,N-P) the mesenchymal induction markers (Fgf8, Pax8 and Lhx1) to E12.5 embryonic kidneys. Although Wnt4 mutant kidneys express Fgf8 (F), they do not express Pax8 and Lhx1 in the mesenchyme (G,H). In Wnt4 mutants, Pax8 and Lhx1 are expressed only in the collecting duct (G,H). Six2TGC-mediated activation of Wnt/ß-catenin pathway causes ectopic expression of the mesenchymal induction markers in both Wnt4 heterozygotes (J,K,L) and mutants (N,O,P).

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

Twitter