Heterogeneity In Processing And Signalling By The Notch Family Of Receptors In Vascular Development And Remodelling.
Funder
National Health and Medical Research Council
Funding Amount
$85,716.00
Summary
Formation and remodelling of the blood vessels is a critical feature of development. In addition, numerous disorders including psoriasis, arthritis, blindness, heart and brain ischemia, neurodegeneration, hypertension, pre-eclampsia, respiratory distress and osteoporosis among others are characterised by defective blood vessel patterning. The significance associated with understanding how Notch genes direct blood vessel formation is paramount, as this knowledge will inform future research.
Functional Analysis Of The Notch Signalling Pathway In The Differentiation And Maintenance Of Pituitary Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$421,320.00
Summary
Many of the processes that are essential for normal bodily function such as growth, the ability to cope with stress, sexual organ development, metabolism and milk production, are controlled by the pituitary gland. This organ is located at the base of the brain and regulates these bodily functions through the release of six different hormones. Formation of the pituitary gland occurs during development of the foetus. This process requires a specific set of genes that shape the pituitary and allow ....Many of the processes that are essential for normal bodily function such as growth, the ability to cope with stress, sexual organ development, metabolism and milk production, are controlled by the pituitary gland. This organ is located at the base of the brain and regulates these bodily functions through the release of six different hormones. Formation of the pituitary gland occurs during development of the foetus. This process requires a specific set of genes that shape the pituitary and allow the hormone secreting cells to arise. Changes in these pituitary formation genes results in underdevelopment of the pituitary in newborn babies. In severe cases, where the pituitary has failed to form completely (panhypopituitarism), these babies are extremely ill and in some instances do not survive. We are studying the genes that belong to the Notch signalling pathway. These genes are important regulators of cell differentiation during the development of the brain, skin, bone and many other tissues. However, the role of the Notch signalling genes in pituitary development is not known. We have shown for the first time that these genes are active during pituitary development. To test the function of these genes in the pituitary, we will generate mouse models that either lack or inappropriately activate these genes. Our results will provide insight into the role of Notch Signalling genes in pituitary development in mice and humans. In this project, we also hope to identify cells in the pituitary that are able to give rise to multiple hormone secreting cell types. These stem cells are of significant clinical importance as they provide an avenue for the development of novel therapies for pituitary disorders in humans, based on the replacement of defective pituitary tissue with functional stem cell derived tissue.Read moreRead less
Investigation Of Delta3 Function And Notch Signalling During Cell Fate Specification In Mouse And Human
Funder
National Health and Medical Research Council
Funding Amount
$221,717.00
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 th ....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.Read moreRead less