Nuclear and cytoplasmatic expression of the Wilms’ tumour (WT1) protein during human embryonic/fetal development.

The Wilms’ tumour gene (WT1) was identified as a gene that maps to human chromosome 11p13 and encode a zinc-finger transcription factor implicated in controlling normal urogenital development. Although WT1 was originally identified as a tumour suppressor, accumulating data indicate its role as potential oncogene influencing proliferation and apoptosis, depending on cellular context. RNA in situ hybridization and immunohistochemical studies showed a dynamic expression profile of WT1 during lifetime in mammals. Apart from the nuclear expression of WT1 in metanephros, its localization in other developing human tissues is still to be defined. Accordingly, the aim of this study is to investigate immunohistochemically the temporal and spatial distribution of WT1 during human ontogenesis from the 5 week of gestational age. WT1 nuclear expression was observed in mesonephric/metanephric glomeruli, metanephric blastema, coelomatic-derived membranes (pleura, peritoneum, serosal surfaces), sex cords, perimullerian mesenchyme, subserosal mesenchyme of gastrointestinal tract and in a subset of spinal motoneurons of anterior horns. Surprisingly, a strong WT1 cytoplasmic expression was identified in skeletal and cardiac muscle cells, endothelial cells of developing blood vessels and in the ependymal layer of spinal cord. In conclusion, the tissue-specific expression of WT1 together with its different nuclear/cytoplasmatic localization suggest that WT1 protein may have shuttling properties, acting as a protein with complex regulator activity in transcriptional/translation processes. The reported cytoplasmic expression of WT1 in human rhabdomyosarcomas and in some vascular tumors strongly suggests an oncofetal expression of this protein.