The evolution of WT1 sequence and expression pattern in the vertebrates

J Kent, A M Coriat, P T Sharpe, N D Hastie, V van Heyningen

Research output: Contribution to journalArticlepeer-review

Abstract

WT1 is a Wilms' tumour predisposition gene, encoding a protein with four C-terminal Kruppel-type zinc fingers, which is also a major regulator of kidney and gonadal development. To pinpoint key regulatory domains involved in development and evolution of the vertebrate genitourinary system, we have isolated WT1 orthologues from all gnathostome classes. Partial nucleotide sequence from chick, alligator, Xenopus laevis and zebrafish reveals extensive conservation. Both the zinc fingers and the transregulatory domain exhibit a high level of similarity in all the species examined. However, of the two alternatively spliced regions only one, the three amino acid KTS insertion between zinc fingers 3 and 4, is found in species other than mammals. The 17 amino acid insertion at the C-terminal end of the transregulatory domain is present only in mammals. Residues with reported human pathological mutations are also unaltered across species, underlining their structural significance. Studies in chick and alligator reveal that the mammalian intermediate mesoderm expression pattern is conserved in birds and reptiles. A wider role in mesodermal differentiation is suggested by expression in some paraxial and lateral mesoderm derivatives.

Original languageEnglish
Pages (from-to)1781-92
Number of pages12
JournalOncogene
Volume11
Issue number9
Publication statusPublished - 2 Nov 1995

Keywords

  • Alligators and Crocodiles
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Biological Evolution
  • Cell Differentiation
  • Chick Embryo
  • Chickens
  • DNA Primers
  • DNA-Binding Proteins
  • Embryo, Nonmammalian
  • Exons
  • Gene Expression
  • Genes, Wilms Tumor
  • Humans
  • In Situ Hybridization
  • Kidney Neoplasms
  • Leucine Zippers
  • Mammals
  • Mesoderm
  • Mice
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Transcription Factors
  • Vertebrates
  • WT1 Proteins
  • Wilms Tumor
  • Xenopus laevis
  • Zebrafish
  • Zinc Fingers

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