Developmental genes in the life cycle of a parasitic flatworm

Tapeworms are a group of more than 10,000 known species adversely affecting the health of both ourselves and our domesticated animals. Their complex life histories centre on the maintenance of a germinative 'neck' region that produces a continuous chain of segments throughout their lives, each replete with male and female reproductive organs capable of producing an enormous number of new infections. Genetic mechanisms underpinning their development are unknown, but have implications for both understanding novel means of therapeutic intervention as well as understanding basic developmental processes in the animal kingdom. This research will examine the roles of Hox and other developmental genes that act to coordinate embryonic axial patterning and other aspects of development throughout the animal kingdom (e.g. establishing which end will develop into the 'head' and which into the 'tail'). By understanding the actions of these genes, this research will resolve fundamental questions regarding how tapeworms became segmented to enable their parasitic lifestyle and how Hox genes are used in the complex development of a parasitic animal. In turn, this will provide a platform for future research on development in other parasitic flatworm groups.

Hox and other homeobox genes will be used to investigate segmentation and other aspects of tapeworm development as well as the evolution of the Hox cluster in a medically and economically important group of metazoan parasites that have been effectively absent from the field of evo devo. A preliminary, degenerate primer-based study of homoebox genes in the model cestode Hymenolepis has recovered anterior, central and posterior-class Hox genes and an initial examination of their expression patterns in adult worms by whole mount in situ hybridization (WMISH) has produced promising results implicating their involvement in basic developmental processes including segmentation and growth of the reproductive organs. A genomic library will be used to screen for additional members of the Hox family and other specific homeoboxes (Cdx, Otx) to be used as regional markers in resolving fundamental questions such as the correct orientation of their anteroposterior axis. Gene expression studies employing WMISH will be extended to understand the role of the Hox family of transcription factors throughout tapeworm ontogeny and their functions will be explored using gene suppression techniques. These data will elucidate developmental mechanisms in tapeworms and allow us to determine the extent to which spatial and temporal collinear expression of Hox genes has been preserved in parasitic groups with complex life cycles. The work will provide the first detailed study of Hox evolution and function in a metazoan parasite and will provide the data by which development in tapeworms can be understood in the wider context of animal evolution.