The expresssion of the Wilms' tumour gene, WT1, during mouse development

• Main Author: Armstrong, J. F.
• Published: University of Edinburgh 1993
• Subjects: 591.35
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.641068

Wilms' tumour (WT), a renal tumour of early childhood, arises as a result of uncontrolled proliferation in the stem cells of the kidney due to an anomaly in their developmental pathway. A strong genetic element is known to be involved in its genesis, with more than one gene being implicated. The first of these, WT1, has recently been isolated and shown to be expressed in a specific pattern in both the developing human kidney and the tumour itself. The purpose of the work presented in this thesis is to examine the role that this gene plays in mouse embryogenesis, a system that lends itself to experimentation more readily than the human. Here, the expression of the mouse homologue of WT1 is examined in three complementary systems; the developing mouse embryo, the kidney as it forms both <i>in vivo-</i> and <i>in vitro</i> and finally, in a possible mouse model for WT. A comprehensive study of the expression pattern of WT1 during development was undertaken, using <i>in situ</i> mRNA hybridization. Expression was first apparent in a small area of the lateral mesoderm in the 9 day embryo. Within 12 hours this had increased markedly, with both the lining of the whole coelomic cavity and the early urogenital ridge being labelled. As development proceeded, expression was initiated in a limited set of tissues which included the metanephros, the mesothelium, the gonads, the spleen, the developing body-wall musculature, the spinal cord and the brain. Expression was present in 15 day embryos but markedly reduced by 19 days with labelling being restricted to the kidney and gonads.