The Role Of Ryk/AF6/Eph Complexes In Neuronal Pathfinding/fasciculation
Funder
National Health and Medical Research Council
Funding Amount
$422,036.00
Summary
During embryonic development nerve cells in the central nervous system have to find the right connections to make with other nerve cells. The process by which nerve cells find the right partners to make connections with is called neuronal pathfinding. Once some nerve cells have made the right connections, other nerve cells attach to these cells and form bundles of nerve fibres. This process is called fasciculation or bundling. This whole process is vital to the normal development and function of ....During embryonic development nerve cells in the central nervous system have to find the right connections to make with other nerve cells. The process by which nerve cells find the right partners to make connections with is called neuronal pathfinding. Once some nerve cells have made the right connections, other nerve cells attach to these cells and form bundles of nerve fibres. This process is called fasciculation or bundling. This whole process is vital to the normal development and function of the central nervous system and the brain. Without the right connections between nerves, information could not be received, processed or sent to organs in the body. We are now starting to discover some of the molecules which control the process of nerve cell pathfinding during development. It has been known for some time that proteins called Eph receptors play an important role in neuronal pathfinding and development of the head region in mice. We have now discovered that two other proteins called Ryk and AF-6 are able to bind to Eph receptors. We have very recently created mice which lack the Ryk protein and these mice have defects in their head deveopment strikingly similarto the head defects seen in mice that lack Eph receptors. We now wish to see whether Ryk mice have defects in neuronal pathfinding and fasciculation as do mice lacking Eph receptors. We also think that Ryk, Af-6 and Eph receptors form a protein complex which can modify cell function. We now wish to explore how this protein complex can do this.Read moreRead less
Dissecting The Molecular Mechanisms Driving Cell Migration During Neurulation Triggered By The Netrin Receptor, Neogenin
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
In humans, abnormalities in brain and spinal cord formation during early embryogenesis result in congenital syndromes such as spina bifida and anencephaly. These defects occur at a rate of 1-1000 pregnancies and are therefore a major contributor to pre- and perinatal deaths. In the early embryo, the brain and spinal cord begin as a hollow tube of cells (the neural tube) that subsequently expands into the complex structures seen at birth. It is known that the neural tube is formed by a complex pr ....In humans, abnormalities in brain and spinal cord formation during early embryogenesis result in congenital syndromes such as spina bifida and anencephaly. These defects occur at a rate of 1-1000 pregnancies and are therefore a major contributor to pre- and perinatal deaths. In the early embryo, the brain and spinal cord begin as a hollow tube of cells (the neural tube) that subsequently expands into the complex structures seen at birth. It is known that the neural tube is formed by a complex process in which early neural cells migrate toward the midline of the embryo and subsequently coalesce. This project seeks to determine the function of one molecular signaling pathway (the neogenin pathway) that has been implicated in driving these cell migration events. We will initially use the frog, Xenopus laevis, as our embryonic model since the developmental processes that form the Xenopus neural tube closely parallel those ocurring in the human embryo. This model will allow us to identify the molecules in the neogenin signaling pathway. We will also create mice that carry a mutation in the neogenin gene so that we can study neogenin function in the mammal. We anticipate that these studies will provide important insights into the development of the central nervous system and also into the aberrant molecular processes underlying neural tube defects in man.Read moreRead less