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Related Experiment Videos

The evolution of WT1 sequence and expression pattern in the vertebrates

J Kent1, A M Coriat, P T Sharpe

  • 1MRC Human Genetics Unit, Western General Hospital, Edinburgh, Scotland, UK.

Oncogene
|November 2, 1995
PubMed
Summary

The WT1 gene is crucial for kidney and gonad development. Its key regulatory domains, including zinc fingers, are highly conserved across vertebrate species, indicating ancient functional importance.

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Area of Science:

  • Developmental Biology
  • Evolutionary Biology
  • Genetics

Background:

  • The WT1 gene is a critical regulator of kidney and gonadal development.
  • WT1 mutations are linked to Wilms' tumour, a kidney cancer.
  • Understanding WT1's evolutionary conservation can elucidate genitourinary system development.

Purpose of the Study:

  • To investigate the evolutionary conservation of WT1 gene orthologues across gnathostome classes.
  • To identify key regulatory domains of WT1 involved in vertebrate genitourinary system development and evolution.

Main Methods:

  • Isolation of WT1 orthologues from various vertebrate species (chick, alligator, Xenopus laevis, zebrafish).
  • Partial nucleotide sequencing and comparative analysis of conserved domains.

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  • Examination of alternative splicing regions and their presence across species.
  • Main Results:

    • High sequence similarity observed in WT1 zinc fingers and transregulatory domains across all examined species.
    • The KTS insertion (3 amino acids) between zinc fingers 3 and 4 is conserved in non-mammalian species.
    • A C-terminal 17 amino acid insertion is unique to mammals.
    • Conserved expression patterns in intermediate mesoderm of chick and alligator, similar to mammals.
    • WT1 expression also noted in other mesodermal derivatives, suggesting a broader role.

    Conclusions:

    • WT1's core regulatory domains are highly conserved throughout vertebrate evolution.
    • Alternative splicing patterns of WT1 differ between mammals and other vertebrates.
    • WT1 plays a conserved role in genitourinary development and potentially broader mesodermal differentiation across vertebrates.