Identifizierung und Charakterisierung von Fibroblasten-Wachstumsfaktoren und -Rezeptoren bei Hydra

FGFs are small signaling polypeptides and most of them act extracellularly. They exist in invertebrates and vertebrates. In the latter between 19 (Gallus gallus) and 27 (Danio rerio) different FGFs are known, while within the invertebrates, the number of FGFs is much lower. The size of FGFs varies between 17 kDa and 34 kDa in vertebrates and between 21 kDa and 86 kDa in invertebrates. The high structural similarity within the typical FGF core region, even across species, allows their classification into seven subfamilies. FGFs are involved in different developmental processes, like limb bud development, establishment of boundaries or tubulogenesis. By binding to an FGF receptor, FGFs control, in a concentration-dependent manner, e.g. cell migration, cell differentiation and cell adhesion. FGFRs are membrane bound receptors and belong to the superfamily of receptor tyrosine-kinases. There are four canonical and one non-canonical FGFR in vertebrates, and up to two canonical and one non-canonical FGFR in invertebrates. In contrast to canonical FGFRs, the non-canonical receptor, FGFRL1, lacks a tyrosine kinase domain and is supposed to be a negative regulator for the FGF/FGFR signaling pathway. Two hypotheses are discussed to explain the evolution of FGFs. One claims that only few FGFs existed in the Urmetazoa, the other one claims that multiple FGFs existed already. In the case of FGFRs, it is assumed that a single ancestral receptor sequence underwent duplication in the invertebrate phyla independently. The four vertebrates FGFRs emerged during a second phase of gene duplication. Very little is known about the FGF/FGFR signaling pathway in Hydra. Earlier studies indicated the presence of one FGF-receptor, FGFRa, and one possible FGF, HvFGF1/2 in Hydra vulgaris Zürich. FGFRa is essential for the bud detachment. In this thesis, I identified the full set of Hydra FGFs and FGFRs, investigated their phylogeny, their gene expression patterns and protein localization. These studies allowed predictions about potential functions as well as the evolution of FGFs and FGFRs. The phylogeny of the Hydra FGFs supports the hypothesis that it was originally only few FGFs. The data suggest, that there were three FGFs in the ancestor of Hydra and Bilateria. The transcription pattern of the four Hydra vulgaris AEP FGFs and the protein localization of FGF-f indicated that the FGFs probably have multiple functions in Hydra. Two more FGFRs, FGFRb and HvFGFRL1 were identified. FGFRb, a second canonical FGFR, might act redundantly to FGFRa, while HvFGFRL1 has the potential to act as a negative regulator of the FGF/FGFR signaling pathway with respect to the differential speed of cell migration into the hypostome and the tentacles. Concerning the number and expression patterns of ligands and receptors, my data shows that the FGF/FGFR tool kit was already complex in the ancestor of Hydra and Bilateria.