Analysis of the role of the Wilms tumour protein in the developing neural crest

Wilms tumour protein (Wt1) was originally discovered to be associated with childhood kidney tumours, but surprisingly recent unpublished results from our laboratory have shown that Wt1 is expressed in developing neural crest cells during embryogenesis. The neural crest is a unique ectodermal tissue as it gives rise to a large range of different cell types, including the enteric nervous system (ENS). Defects in the ENS have been identified as cause for a potentially lethal congenital abnormality, Hirschsprung’s Disease, which affects 1 in 5000 children who are born with defective bowel function due to the lack of ENS neurons. The cause of this disease is unknown.

The aim of this project will be to investigate the role of Wt1 during neural crest development in order to find if it is involved in Hirschprung’s disease. To do this, we will identify target genes for Wt1 in the neural crest, in order to understand the cellular and molecular mechanisms in which Wt1 is involved. The project will involve training in a broad range of modern molecular-, cellular- and developmental biology research techniques, including mouse genetics, gene expression analysis and silencing approaches, together with primary tissue culture experiments.