A tight co-ordination between cell proliferation and differentiation is essential to the correct development of all multi-cellular organisms. The intercellular signalling pathway triggered by the receptor Notch is central in maintaining the co-ordination between cell cycle control and neuronal cell fate acquisition during vertebrate development. However, the mechanistic details of its action are still ill understood. This is largely due to the great anatomical and genetic complexity of the available vertebrate model systems. The ascidian, Ciona intestinalis is a basal chordate.
It is phylogenetically close to vertebrates, but morphologically and genetically very simple and well characterized. We propose to exploit the simple peripheral nervous system of Ciona intestinalis to study the interactions between Notch signalling and the cell cycle control mechanisms in chordates. Our project aims first at understanding the respective contributions of the Notch pathway and the cell cycle control machinery in defining the number of peripheral nervous system neurons in Ciona larvae.
In a second time, we will explore the connections between the two mechanisms. To this end, we will take advantage of the amenability of Ciona embryos to a large spectrum of developmental and molecular biology manipulations. The project will result in a better comprehension of the mechanisms, which regulate cell proliferation and differentiation in chordates. This may in turn lead to the identification of new genes involved in human proliferative disorders.
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