The Wnt family of secreted signalling molecules control a wide range of developmental processes in all metazoans. In this investigation, I have concentrated on the role that members of this family play during the development of (l) the somites and (2) the neural crest. Finally we have isolated a novel component of the Wnt signalling pathway called Naked Cuticle and I investigated the role that this protein may play in both the previously mentioned processes. (l) In higher vertebrates the paraxial mesoderm undergoes a mesenchymal to epithelial transformation to form segmentally organised structures called somites. Experiments have shown that signals originating from the ectoderm overlying the somites or from midline structures are required for the formation of the somites but, their identity has yet to be determined. Wnt6 is a good candidate as a somite epithelialisation factor from the ectoderm since it is expressed in this tissue. In this study we show that injection of Wnt6-producing cells beneath the ectoderm at the level of segmental plate or lateral to the segmental plate leads to the formation of numerous small epithelial somites. We show that Wnts are indeed responsible for the epithelialisation of somites by applying Wnt antagonists which result in the segmental plate being unable to form somites. These results show that Wnt6, the only member of this family to be localised to the chick paraxial ectoderm is able to regulate the development of epithelial somites and that cellular organisation is pivotal in the execution of the differentiation programmes. (2) The neural crest is a population of multipotent progenitor cells that arise from the neural ectoderm in all vertebrate embryos and form a multitude of derivatives including the peripheral sensory neurons, the enteric nervous system, Schwann cells, pigment cells and parts of the craniofacial skeleton. The induction of neural crest relies on an ectodermally derived signal, but the identity of the molecule performing this role in amniotes is not known. Here we show for the first time that Wnt6, a protein expressed in the ectoderm, induces neural . crest production. (3) The intracellular response to Wnt signalling depends on the choice of signalling cascade activated in the responding cell. Cells can activate either the canonical pathway that modulates gene expression to control cellular' differentiation and proliferation, or the noncanonical pathway that controls cell polarity and movement. Recent work has identified the protein Naked Cuticle to ac\ as an intracellular switch to promote the non-canonical pathway at the expense of the canonical pathway. We have cloned chick Naked Cuticle-l (cNkd-l) and show that it is expressed in a·'dynamic manner during early embryogenesis. We show that it is expressed in the somites and in particular r~gions where cells are undergoing movement. Lastly we show that the expression of cNkd-l is regulated by- Writ expression originating from the neural tube. This study provides evidence that non-canonical Wnt signalling plays a part in somite development.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:487307 |
| Date | January 2007 |
| Creators | Schmidt, Corina Ursula |
| Publisher | Royal Veterinary College (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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