Gene expression analysis of Xrel3-induced tumours in Xenopus laevis

Xenopus rel3 (Xrel3) is one of five Xenopus members of the Rel/Nuclear Factor kappa B (NF-kB) family of transcriptional activators. The role of Xrel3 in early embryonic development is unclear, however, its spatially and temporally restricted pattern of expression in larval and tadpole stages suggests a potential role in embryonic patterning. Overexpression of synthetic Xrel3 messenger RNA (mRNA) in the animal pole of Xenopus embryos induces the formation of tumours on the surface of embryos. Reverse transcription polymerase chain reaction (RT-PCR) was used in this study to investigate and identify genes that are activated in response to Xrel3 overexpression. My results show that sonic hedgehog (shh) glil, otx-2 and the fibroblast growth factors, fgf-8 and efgf(ii), are upregulated in response to Xrel3 overexpression. Interestingly, these genes are axial patterning genes required for the development of dorsal and anterior body structures, whose normal expression patterns overlap that of Xrel3 in neurula and larval stage embryos. In addition, Glil, Shh and Fgfs play normal roles in promoting cell proliferation and regulating the cell cycle. This suggests that perhaps the role of Xrel3 in development is to regulate cell proliferation and hence the differentiation of certain structures of the nervous system. The effect of Xrel3 overexpression on the levels of glil, shh and otx-2 was not an immediate one, but the use of the differential display technique has led to the identification of a potentially novel gene activated by Xrel3. The identification and characterization of the specific components of the Xrel3 signalling pathway and the biochemical nature by which Xrel3 exerts its influence will provide us with an insight into the mechanism by which it functions in development and cancer