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PMID:19060336

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Citation

Yu, J, Carroll, TJ, Rajagopal, J, Kobayashi, A, Ren, Q and McMahon, AP (2009) A Wnt7b-dependent pathway regulates the orientation of epithelial cell division and establishes the cortico-medullary axis of the mammalian kidney. Development 136:161-71

Abstract

The mammalian kidney is organized into a cortex where primary filtration occurs, and a medullary region composed of elongated tubular epithelia where urine is concentrated. We show that the cortico-medullary axis of kidney organization and function is regulated by Wnt7b signaling. The future collecting duct network specifically expresses Wnt7b. In the absence of Wnt7b, cortical epithelial development is normal but the medullary zone fails to form and urine fails to be concentrated normally. The analysis of cell division planes in the collecting duct epithelium of the emerging medullary zone indicates a bias along the longitudinal axis of the epithelium. By contrast, in Wnt7b mutants, cell division planes in this population are biased along the radial axis, suggesting that Wnt7b-mediated regulation of the cell cleavage plane contributes to the establishment of a cortico-medullary axis. The removal of beta-catenin from the underlying Wnt-responsive interstitium phenocopies the medullary deficiency of Wnt7b mutants, suggesting a paracrine role for Wnt7b action through the canonical Wnt pathway. Wnt7b signaling is also essential for the coordinated growth of the loop of Henle, a medullary extension of the nephron that elongates in parallel to the collecting duct epithelium. These findings demonstrate that Wnt7b is a key regulator of the tissue architecture that establishes a functional physiologically active mammalian kidney.

Links

PubMed PMC2685965 Online version:10.1242/dev.022087

Keywords

Animals; Body Patterning; Cell Division; Cyclin-Dependent Kinase Inhibitor p57/metabolism; Epithelial Cells/cytology; Epithelial Cells/metabolism; Female; Kidney Cortex/embryology; Kidney Medulla/cytology; Kidney Medulla/embryology; Kidney Medulla/metabolism; Kidney Tubules, Collecting/cytology; Kidney Tubules, Collecting/embryology; Kidney Tubules, Collecting/metabolism; Loop of Henle/cytology; Loop of Henle/embryology; Loop of Henle/metabolism; Mammals/embryology; Mice; Mutation/genetics; Nephrons/cytology; Nephrons/embryology; Nephrons/metabolism; Proto-Oncogene Proteins/metabolism; Signal Transduction; Ureter/cytology; Ureter/embryology; Ureter/metabolism; Wnt Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:WNT7B

acts_upstream_of_or_within

GO:0016332: establishment or maintenance of polarity of embryonic epithelium

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3793280

P

  • occurs_in:(EMAPA:28407)

Seeded From UniProt

complete

MOUSE:WNT7B

acts_upstream_of_or_within

GO:0003338: metanephros morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3793280

P

Seeded From UniProt

complete

MOUSE:WNT7B

acts_upstream_of_or_within

GO:0060560: developmental growth involved in morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3793280

P

  • occurs_in:(EMAPA:19280)

Seeded From UniProt

complete

MOUSE:WNT7B

acts_upstream_of_or_within

GO:0060070: canonical Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3793280

P

  • occurs_in:(CL:0000134)
  • occurs_in:(EMAPA:18326)

Seeded From UniProt

complete

MOUSE:WNT7B

acts_upstream_of_or_within

GO:0072236: metanephric loop of Henle development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3793280

P

  • results_in_development_of:(EMAPA:19280)

Seeded From UniProt

complete

MOUSE:WNT7B

acts_upstream_of_or_within

GO:0072207: metanephric epithelium development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3793280

P

  • results_in_development_of:(EMAPA:28407)

Seeded From UniProt

complete

MOUSE:WNT7B

acts_upstream_of_or_within

GO:0072205: metanephric collecting duct development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3793280

P

  • results_in_development_of:(EMAPA:28407)

Seeded From UniProt

complete

MOUSE:WNT7B

acts_upstream_of_or_within

GO:0072061: inner medullary collecting duct development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3793280

P

  • results_in_development_of:(EMAPA:28407)

Seeded From UniProt

complete

MOUSE:WNT7B

acts_upstream_of_or_within

GO:0072060: outer medullary collecting duct development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3793280

P

  • results_in_development_of:(EMAPA:28407)

Seeded From UniProt

complete

MOUSE:WNT7B

acts_upstream_of_or_within

GO:0072054: renal outer medulla development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3793280

P

  • results_in_development_of:(EMAPA:18326)|results_in_development_of:(EMAPA:31414)

Seeded From UniProt

complete

MOUSE:WNT7B

acts_upstream_of_or_within

GO:0072053: renal inner medulla development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3793280

P

  • results_in_development_of:(EMAPA:18326)|results_in_development_of:(EMAPA:31414)

Seeded From UniProt

complete

MOUSE:CTNB1

acts_upstream_of_or_within

GO:0003338: metanephros morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CTNB1

acts_upstream_of_or_within

GO:0060070: canonical Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000134)
  • occurs_in:(EMAPA:18326)

Seeded From UniProt

complete

MOUSE:CTNB1

acts_upstream_of_or_within

GO:0072054: renal outer medulla development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • results_in_development_of:(EMAPA:18326)|results_in_development_of:(EMAPA:31414)

Seeded From UniProt

complete

MOUSE:CTNB1

acts_upstream_of_or_within

GO:0072053: renal inner medulla development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • results_in_development_of:(EMAPA:18326)|results_in_development_of:(EMAPA:31414)

Seeded From UniProt

complete

MOUSE:CTNB1

acts_upstream_of_or_within

GO:0060070: canonical Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(EMAPA:18326)
  • occurs_in:(CL:0000134)

Seeded From UniProt

complete

MOUSE:CTNB1

acts_upstream_of_or_within

GO:0072053: renal inner medulla development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

results_in_development_of:(EMAPA:18326)|results_in_development_of:(EMAPA:31414)

Seeded From UniProt

complete

MOUSE:CTNB1

acts_upstream_of_or_within

GO:0072054: renal outer medulla development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

results_in_development_of:(EMAPA:18326)|results_in_development_of:(EMAPA:31414)

Seeded From UniProt

complete

MOUSE:CTNB1

acts_upstream_of_or_within

GO:0003338: metanephros morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

has_participant:(EMAPA:18326)|has_participant:(EMAPA:31414)

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.