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Canonical Wnt Signaling Pathway02:54

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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...
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Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
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Spatiotemporal distribution of Wnt signaling pathway markers in human congenital anomalies of kidney and urinary

Ilija Perutina1, Nela Kelam2, Mirko Maglica3

  • 1Department of Anatomy, University of Mostar, School of Medicine, Mostar 88000, Bosnia and Herzegovina; Department of Neurosurgery, University Clinical Hospital Mostar, Mostar 88 000, Bosnia and Herzegovina.

Acta Histochemica
|February 5, 2025
PubMed
Summary

Wnt signaling pathway regulation is crucial for normal human fetal kidney development. Disruptions in this pathway are observed in congenital anomalies of the kidney and urinary tract (CAKUT), impacting kidney differentiation.

Keywords:
CAKUTCanonical Wnt signalingDishevelled-1InversinKidney morphogenesisα-tubulinβ-catenin

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Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Nephrology

Background:

  • The Wnt signaling pathway plays a critical role in embryonic development, including kidney organogenesis.
  • Congenital anomalies of the kidney and urinary tract (CAKUT) represent a spectrum of developmental abnormalities with significant clinical impact.
  • Understanding the molecular mechanisms underlying normal and abnormal kidney development is essential for therapeutic advancements.

Purpose of the Study:

  • To investigate the spatiotemporal expression of Wnt pathway markers during human fetal kidney development.
  • To compare these expression patterns in healthy kidneys versus kidneys affected by CAKUT.
  • To elucidate the role of Wnt pathway crosstalk in nephrogenesis and CAKUT.

Main Methods:

  • Human fetal kidneys (18-38 weeks) with various CAKUT phenotypes and controls were analyzed.
  • Double immunofluorescence microscopy was employed to assess protein expression of key Wnt markers.
  • Quantitative analysis and regression modeling were used to evaluate expression dynamics.

Main Results:

  • Decreased acetylated α-tubulin during normal development; elevated in horseshoe kidneys.
  • Reduced inversin in hypoplastic/duplex kidneys; increased DVL-1 in dysplastic kidneys.
  • Aberrant β-catenin expression in CAKUT kidneys suggests impaired Wnt pathway switching.

Conclusions:

  • The balance between canonical and non-canonical Wnt signaling is vital for normal nephrogenesis.
  • Dysregulation of Wnt pathway crosstalk contributes to the pathogenesis of CAKUT.
  • Targeting Wnt signaling pathways may offer potential therapeutic strategies for kidney developmental disorders.