Investigation of Delta3 function and Notch signalling during cell fate specification in mouse and human

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/142006

Funding Status
Closed

Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the .

Funded Activity Summary

This project seeks to understand how cells within the developing embryo are produced and how they are given a specific identity. These processes often require the cell to make a decision about what type of cell it will become. We are using the Delta3 gene, which is present in humans and in the mouse, as a tool for our investigations. Delta3 is expressed at the surface of the cell and Notch (its receptor) is present on the surface of neighbouring cells. Delta3 on one cell will bind to Notch on the neighbouring cell and activates Notch. When Notch is activated in a cell it pushes the cell to make its decision. This project aims to determine what exactly is the function of Delta3 in mammals and how at the level of the individual cell this protein exerts its effects. We have generated a mouse in which the Delta3 gene is no longer active and have observed that embryos do not develop normally. We will explore these defects (which affect the skeleton and the brain) in detail in order to define their origins. We will also use these abnormal mice to identify genes, which require the function of Delta3 for their normal activity. It is not only important to define the function of Delta3 in mammals but also to determine this protein functions. We wish to know how exactly Delta3 interacts with Notch. That is, which part of the Delta3 protein binds to which part of the Notch protein. We can address this by modifying the Delta3 protein in small (but revealing ways) and see if it can still bind the Notch receptor in a cell culture assay. Our studies have relevance to humans because recently it has been shown that Delta and Notch are associated with a human syndrome (spondylocostal dysostosis) in which individuals suffer from abnormal skeletons.

Funded Activity Details

Start Date: 01-01-2001

End Date: 01-01-2003

Funding Scheme: NHMRC Project Grants

Funding Amount: $221,717.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Genetic Development (Incl. Sex Determination)

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

Brain and Skeletal Development | Clinical Genetics | Congenital Brain Defects | Congenital Skeletal Defects | Gastrulation | Mutant Analysis | Notch Signalling Pathway | Stem Cells

Related Links