THE EVOLUTION OF WT1 SEQUENCE AND EXPRESSION PATTERN IN THE VERTEBRATES

WT1 is a Wilms' tumour predisposition gene, encoding a protein with fo ur C-terminal Kruppel-type zinc fingers, which is also a major regulat or of kidney and gonadal development, To pinpoint key regulatory domai ns involved in development and evolution of the vertebrate genitourina ry system, we have isolated WT1 orthologues from all gnathostome class es. Partial nucleotide sequence from chick, alligator, Xenopus laevis and zebrafish reveals extensive conservation, Both the zinc fingers an d the transregulatory domain exhibit a high level of similarity in all the species examined. However, of the two alternatively spliced regio ns 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 inse rtion at the C-terminal end of the transregulatory domain is present o nly in mammals, Residues with reported human pathological mutations ar e also unaltered across species, underlining their structural signific ance, Studies in chick and alligator reveal that the mammalian interme diate 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.