Coates, Juliet Clare; (1999) Armadillo Homologues in Dictyostelium discoideum. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Armadillo family proteins are present throughout the animal kingdom. In fruit flies, frogs, fish and mammals these proteins are essential for correct embryonic patterning via the Wnt/Wingless signal transduction pathway, acting downstream of glycogen synthase kinase-3 (gsk3). In addition, the same proteins are essential for regulated cell to cell adhesion. These proteins must be tightly controlled to prevent the growth and metastasis of tumours in the adult organism. However, the relationship between their developmental and adhesive role is not well understood at present. The cellular slime mould Dictyostelium discoideum is a model system in which to study multicellular development and cell adhesion. The Dictyostelium homologue of glycogen synthase kinase-3, gskA, is essential for the correct proportioning of cell types during development. The downstream targets of gskA remained to be discovered at the start of this work. I have isolated an Armadillo family gene, aardvark (aar), in Dictyostelium and created a knock-out mutant. The mutant phenotype demonstrates that aar has an important role in the later stages of development. Aardvark is crucial for defining the final structure of the fruiting body, particularly the assembly of the stalk tube and its associated cell-cell adhesion junctions. Perturbation of this structure in the aar mutant leads to a duplication of the developmental axis. Aar also has a cell-autonomous role, promoting the terminal differentiation of stalk and spore cells. Furthermore, I present evidence that two other Armadillo homologues are also present in Dictyostelium. These proteins are developmentally regulated and their levels and distribution are altered in a gskA- mutant. This thesis suggests that the molecular control of pattern formation and cell to cell adhesion may be very highly conserved throughout evolution and that in Dictyostelium, as in animals, Armadillo homologues act to coordinate morphogenesis and cell identity.

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