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Content archived on 2024-05-27

Control of cell differentiation in the zebrafish gut : role of the notch pathway

Objective

The renewal of gut cells requires the correct control of stem cell proliferation and differentiation. Defects in these key events are responsible for pathologies, such as cancers and developmental abnormalities. The evolutionarily conserved Notch signaling pathway is implicated in the control of cell proliferation and differentiation. The role of this pathway in gut will be primarily studied in zebra fish which is suitable for in vivo experiments. We will first describe the normal pattern of cell types and population dynamics in the zebra fish hindgut. This part will require the use of a reporter gene such as GFP. On the basis of these observations, the analysis will then be performed in Notch pathway zebra fish mutants already available (mind bomb, after eight, deadly seven) or in zebra fishes with artificial gene misexpression. Finally, gut cell differentiation studies will also be performed in mice carrying mutations of the Notch signaling pathway. Because most of the mutations are embryonic lethal, this study will require to graft embryonic mouse gut rudiments sub-multaneous into nude mice and study the development and differentiation of the segments of gut. Results should show if the same conclusions are true for zebra fish and mouse, and should help to gain insight into mechanisms of vertebrate gut development.

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Funding Scheme

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RGI - Research grants (individual fellowships)

Coordinator

CANCER RESEARCH UK
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