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Abstract

Axial muscles in the trunk and tail are important for stabilization and locomotion of the body. In jawed vertebrates, these muscles are further divided into the epaxial (dorsal) and the hypaxial (ventral) muscles. The epaxial muscles eventually cover the neural tube to form the muscles of the back. While it is well described how these muscles differentiate from the somites during early development, it is only poorly understood how the epaxial myotome further develops to form the muscles of the back. The spontaneous medaka (Oryzias latipes) mutant Double anal fin (Da) exhibits an unique axial muscle phenotype where the epaxial muscles fail to cover the neural tube during embryonic development. Recent studies showed that the mutant has a mutation in the somite enhancer region of zic1/zic4, suggesting a role of the transcription factors Zic1/Zic4 as dorsalization factors during late somite development. In this thesis, I elucidated the regulation and the developmental process underlying dorsal somite extension, which ultimately gives rise to epaxial myotome covering the neural tube. Firstly, I addressed the regulation of zic1/zic4 expression by the canonical Wnt signaling pathway during late somite development. I examining the expression of zic1/zic4 after manipulation of the Wnt signaling pathway and performed a ChIP-seq against b-catenin. I could show that zic1/zic4 are direct downstream targets of the canonical Wnt signaling pathway. Next, I found that after the onset zic1/zic4 expression in Wt dorsal somites the proliferative activity of dorsal dermomyotome cells is reduced. Additionally, during somite extension these dermomyotome cells form numerous, large protrusions extending dorsally. This process probably guides the myotome towards the top of the neural tube. In the Da mutant, however, both reduction of cell proliferation and extensive protrusive behavior of dorsal dermomyotome cells was not observed. Furthermore, I identified a direct downstream target of zic1, wnt11r, as additional dorsalization factor. Knockdown of Wnt11r in Wt embryos recapitulated the ventralized somite phenotype of the Da mutant, whereas injection of Wnt11 protein could partially rescue the Da mutant phenotype. By inhibiting the Wnt/Ca2+ signaling pathway, I found that Wnt11r probably acts through this non-canonical Wnt signaling pathway during somite extension. In summary, my results propose that the regulation of wnt11r by zic1/zic4 during late somite development is essential for dorsal somite extension which is key for the morphology of epaxial trunk muscles.