Dokument

Summary:
This thesis deals with the mapping and cloning of trapped (tpd), a novel zebrafish mutant found to disrupt an ortholog of Trap230, a member of the Mediator complex. Mediator is a coactivator complex transducing the interaction of DNA-binding transcription factors with RNA polymerase II. The vertebrate Sox9 transcription factor directs the development of neural crest, otic placodes, cartilage, and bone. In zebrafish, there are two Sox9 orthologs, Sox9a and Sox9b, which together perform the functions of the single-copy tetrapod Sox9. The mutant phenotypes of tpd and the Sox9a/Sox9b double mutant are remarkably similar. The results of this thesis show that Trap230 is required for Sox9 activity. In addition, I show that Trap230 is required for an early step in pectoral fin induction, indicating that it also participates in Sox9-independent signaling events. Moreover, additional phenotypes in brain, eye, heart, muscle and gut development as well as axon guidance and a general downregulation phenotype of fibroblast growth factor expression in tpd mutants are described. These phenotypes may or may not be Sox9- dependent. This is the first characterisation of a vertebrate Trap230 mutant, and reveals a surprisingly specific requirement for Trap230 in mediating Sox9 activity.

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