%0 Generic %A Teo, Regina Mei Mei %D 2005 %F heidok:5567 %K Wnt Cascade , Hydractinia , Frizzled %R 10.11588/heidok.00005567 %T The Wnt Casade and Stem Cell Fate in a Basic Metazoan %U https://archiv.ub.uni-heidelberg.de/volltextserver/5567/ %X The WNT signalling pathways have numerous controlling functions in embryonic development, pattern and axis formation of animals, but also play roles in sustained normal development. There are currently three known WNT signalling pathways, of which the canonical pathway is the most studied. This pathway functions not only in the establishment of the anterior-posterior axis and in cell differentiation, and is the only pathway known to play a role in stem cell fate and maintenance within many of the chordate metazoans. This work served to establish if such a role has already evolved early in metazoan phylogeny by using Hydractinia, a primitive eumetazoan as a model. This work established the presence of a WNT pathway in the hydrozoan Hydractinia. The WNT receptor in Hydractinia, He-frizzled, has been cloned and in situ expression in the life cycle suggest its putative function in budding and regeneration of polyps and in the proliferation of cells during the course of the normal development of the animal. Furthermore, the Hydractinia Frizzled(s) is the first gene from the WNT cascade(s) that was found to be expressed in cnidarian stem cells. Functional studies were carried out using inhibitors to a key enzyme of the canonical WNT pathway, GSK-3ß. Such an inhibition simulates the effect of the Wnt signal. Changes to colony morphology and effects on the stem cell population of Hydractinia were observed. Inhibitors caused ectopic formation of tentacles and heads, and also resulted in the formation of multiheaded polyps. Short treatment caused an initial high proliferation of cells followed by highly significant numbers of I-cells and a few days later, the I-cell differentiated products, namely the nerve and stinging cells. Long term exposure to the inhibitor led to slower growth of the colony, higher numbers of oogonia-like structures and an absence/lack of oocyte and eggs. All these data lend support the multiple functions the WNT pathway plays in this cnidarian and its involvement in the recruitment of stem cell derivatives from the population of I-cells. In a separate study, an attempt to study the fate of closely related chimeric partners in Hydractinia was carried out using microsatellites. An enrichment protocol gave high numbers of microsatellites compared to traditional shotgun methods. There exist microsatellites within Hydractinia, however efforts to find a locus polymorphic enough to discriminate between two closely related kin failed.