Morphogen gradients have long been proposed as a mechanism of developmental patterning. This mechanism requires an individual cell to be able to measure at least two concentration thresholds of a single signalling molecule and to make at least three different cell fate decisions. The mechanism by which cells are able to make these quantitative decisions is not at all well understood. One example of a morphogen response is that of the induction of mesoderm in <I>Xenopus</I> animal cap cells by activin. The grade of mesoderm induced is dependent on the concentration of activin. In this dissertation the induction of mesoderm in animal cap cells by activin is used as a model system for the investigation of how cells determine their response to a morphogen gradient. First, the <I>in vivo</I> role of activin is demonstrated with the use of a novel dominant negative receptor. Second, overexpression of cloned activin receptors is used to show that cells can use a single affinity receptor to generate the different responses to a morphogen, rather than by using different affinity receptors. Third, a new assay has been developed in order to make quantitative measurements for how cells respond to a morphogen. Using this assay it has been shown that cells first respond to activin when only 2% of their receptors are occupied and can switch response when 6% of their receptors are filled. It has also been shown that cells measure the absolute number of their occupied receptors and not the ratio of occupied to unoccupied. Fourth, potential signal transduction components, downstream of the activin receptor, are tested for their involvement in activin signal transduction from receptors to the nucleus. Fifth, the involvement of another signalling pathway, the Wnt pathway, is investigated in the response to activin. It is shown that there is cooperativity between activin signalling and Wnt signalling for the induction of some, but not all, responses to activin and that this cooperativity is reciprocal.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:598719 |
| Date | January 1998 |
| Creators | Dyson, S. |
| Publisher | University of Cambridge |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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