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Related Concept Videos

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The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
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Related Experiment Video

Updated: May 30, 2026

Analysis of Zebrafish Kidney Development with Time-lapse Imaging Using a Dissecting Microscope Equipped for Optical Sectioning
10:05

Analysis of Zebrafish Kidney Development with Time-lapse Imaging Using a Dissecting Microscope Equipped for Optical Sectioning

Published on: April 7, 2016

AHR regulates WT1 genetic programming during murine nephrogenesis.

M Hadi Falahatpisheh1, Adrian Nanez, Kenneth S Ramos

  • 1Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, Kentucky, United States of America.

Molecular Medicine (Cambridge, Mass.)
|August 25, 2011
PubMed
Summary

Aryl hydrocarbon receptor (AHR) disrupts kidney development by interfering with Wilms tumor suppressor gene (WT1) signaling. AHR downregulation affects key developmental genes, highlighting a molecular target for renal developmental interference.

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Organ Culture and Whole Mount Immunofluorescence Staining of Mouse Wolffian Ducts
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Organ Culture and Whole Mount Immunofluorescence Staining of Mouse Wolffian Ducts

Published on: January 13, 2017

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Last Updated: May 30, 2026

Analysis of Zebrafish Kidney Development with Time-lapse Imaging Using a Dissecting Microscope Equipped for Optical Sectioning
10:05

Analysis of Zebrafish Kidney Development with Time-lapse Imaging Using a Dissecting Microscope Equipped for Optical Sectioning

Published on: April 7, 2016

Organ Culture and Whole Mount Immunofluorescence Staining of Mouse Wolffian Ducts
09:16

Organ Culture and Whole Mount Immunofluorescence Staining of Mouse Wolffian Ducts

Published on: January 13, 2017

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Toxicology

Background:

  • Chronic kidney disease (CKD) origins are linked to early developmental programming influenced by environmental factors.
  • The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor implicated in various biological processes.

Purpose of the Study:

  • To investigate the role of AHR in murine renal development.
  • To elucidate the molecular mechanisms by which AHR interferes with kidney differentiation, specifically its interaction with Wilms tumor suppressor gene (WT1) signaling.

Main Methods:

  • Comparative analysis of embryonic kidneys from wild-type and AHR-deficient (Ahr⁻/⁻) mice at gestation day 14.
  • Assessment of renal differentiation markers, including condensation in the nephrogenic zone and differentiated structure counts.
  • Gene expression analysis (mRNA levels) of key developmental genes (Wt1 splice variants, Igf-1 rec., Wnt-4, E-cadherin, sfrbp-1).
  • Protein level analysis of WT1 (52 kDa and 40-kDa isoforms).
  • AHR knockdown experiments in wild-type embryonic kidney cells to mimic AHR deficiency effects.

Main Results:

  • Ahr⁻/⁻ mouse embryos exhibited reduced renal condensation and fewer differentiated structures compared to wild-type controls.
  • Deficits in Ahr⁻/⁻ kidneys correlated with increased (+) 17aa Wt1 splice variant expression and reduced levels of 52 kDa WT1 protein.
  • Downstream effects included decreased mRNA levels of Igf-1 rec., Wnt-4, and E-cadherin in Ahr⁻/⁻ kidneys.
  • AHR knockdown in wild-type cells replicated these findings, showing increased (+) 17aa Wt1 mRNA and altered WT1 protein levels.
  • AHR downregulation also reduced Igf-1 rec., Wnt-4, sfrbp-1, and E-cadherin mRNAs.

Conclusions:

  • Aryl hydrocarbon receptor (AHR) disrupts murine renal differentiation by interfering with Wilms tumor suppressor gene (WT1) signaling.
  • The interaction between AHR and WT1 is a critical molecular pathway influencing kidney development.
  • Understanding this AHR-WT1 axis provides potential targets for addressing renal developmental abnormalities.