Wnt-Ryk Signaling In The Establishment Of Major Axon Tracts In The Embryonic Mouse Brain
Funder
National Health and Medical Research Council
Funding Amount
$513,946.00
Summary
The corpus callosum is the major interhemispheric commissure in the human brain, comprising approximately 3 million myelinated fibers which connect homologous regions in the neocortex. To date more than 50 different human congenital syndromes have been described in which the corpus callosum does not form leading to epilepsy and mental retardation. We have identified a new guidance molecule (Ryk) which is crucial for corpus callosum formation. This project aims to dissect that molecular mechanism ....The corpus callosum is the major interhemispheric commissure in the human brain, comprising approximately 3 million myelinated fibers which connect homologous regions in the neocortex. To date more than 50 different human congenital syndromes have been described in which the corpus callosum does not form leading to epilepsy and mental retardation. We have identified a new guidance molecule (Ryk) which is crucial for corpus callosum formation. This project aims to dissect that molecular mechanisms controlling Ryk signaling during corpus callosum development. Our analysis of Ryk function will advance our understanding of the molecular mechanisms underlying the formation of this important commissure.Read moreRead less
Molecular And Cellular Mechanisms Of Axon Guidance In The Vertebrate Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$330,735.00
Summary
There are, at least, two major obstacles that have to be overcome in the design of therapies to assist the repair of injured brain tissue. First, the nerve cells that are damaged have to be encouraged to regrow - typically this regrowth is inhibited in the brain; and second, this regrowth has to be directed so that the correct connections are re-established. This project will begin to unravel some of the mechanisms that nerve cells use to wire up together during development. This information can ....There are, at least, two major obstacles that have to be overcome in the design of therapies to assist the repair of injured brain tissue. First, the nerve cells that are damaged have to be encouraged to regrow - typically this regrowth is inhibited in the brain; and second, this regrowth has to be directed so that the correct connections are re-established. This project will begin to unravel some of the mechanisms that nerve cells use to wire up together during development. This information can be used to assist in trying to modulate and facilitate directed regrowth following injury.Read moreRead less
Membrane Fusion In Axonal Regeneration: Molecules And Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$461,597.00
Summary
Limited nerve regeneration is the main obstacle for recovery from spinal cord and brain injuries. Understanding the cellular and molecular mechanisms underlying axonal regeneration is an essential step toward the development of novel effective therapies to enhance this process. In this proposal, we use the powerful molecular and genetic tools available for the small nematode worm C. elegans to identify and study axonal regeneration and discover the key molecules involved.
Dissecting The Role Of RYK In Cortical Neuron Specification And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$1,039,028.00
Summary
Correct production of neuronal subtypes within the neocortex is essential for coordinated brain activity and higher-order functions. Understanding how newborn neurons decide which subtype to adopt is critical as incorrect neuron identity has profound consequences for neocortical function and is associated with schizophrenia and mental disability. We have recently linked one molecule, RYK, to schizophrenia. In this project we will explore how Ryk influences cortical neuron fate.
Deciphering The Mechanisms Underlying LRP-mediated Axon Guidance
Funder
National Health and Medical Research Council
Funding Amount
$370,659.00
Summary
Nerve damage can develop post injury or disease and are often very debilitating, slow to heal and cause increased pain. Our work aims to examine a new class of molecules that we show can activate selected fat-receptors on nerve cells to guide the growth of regenerating nerves. We will determine how these receptors function with the aim of developing a novel class of therapeutics directed at healing nerve damage.
The Role Of Store-operated Calcium Entry In Neuronal Development
Funder
National Health and Medical Research Council
Funding Amount
$353,140.00
Summary
Defects in brain development can manifest in a range of disorders including autism and mental retardation. The highly complex, precise network that is our nervous system forms during development. Our work will determine the role of key proteins in guiding developing neurons. Understanding the function of such proteins will improve our ability to predict the outcome caused by mutations in these proteins, in the developing foetus.
The Role Of Membrane Phospholipids In Regenerative Axonal Fusion
Funder
National Health and Medical Research Council
Funding Amount
$571,950.00
Summary
Injuries to the nervous system can cause lifelong disabilities due to ineffective repair of the damaged nerve fibres. Our previous research has identified a highly efficient mechanism that occurs in nematode worms that allows severed nerves to fuse back together. We will now focus on understanding precisely how this mechanism works, and investigate its utility in repairing nerves that don’t normally utilise this repair mechanism.
Astroglial Remodelling Of The Interhemispheric Midline Is Regulated By Deleted In Colorectal Cancer (DCC) Signalling And Is Required For Corpus Callosum Formation
Funder
National Health and Medical Research Council
Funding Amount
$669,400.00
Summary
The integration of information between the brain hemispheres occurs via a large bundle of connecting nerve fibres called the corpus callosum. People with a genetic mutation in DCC display mirror movement disorder and some have a severe brain defect where the corpus callosum fails to form, but at present we don’t understand the function of this gene. In this study we will investigate how DCC functions in early brain development to regulate corpus callosum formation and mirror movement disorder.
Cyclic-nucleotide-dependent Regulation Of Axon Guidance Sensitivity
Funder
National Health and Medical Research Council
Funding Amount
$527,338.00
Summary
Problems in wiring up the brain underlie several nervous system disorders. The goal of this project is to understand better how this wiring normally forms. This will ultimately lead to a better understanding of what can go wrong with brain wiring, and how to fix such problems. It will also lead to a better understanding of how to make axons regenerate after injury.
DCC-Robo Interactions Cooperate To Regulate Callosal Axon Guidance
Funder
National Health and Medical Research Council
Funding Amount
$383,422.00
Summary
In order for the brain to function, the correct connections between neurons must be formed during development. These connections, formed by the axonal processes of neurons, are able to find their synaptic targets by sensing molecular cues within the brain that guide them, by attraction or repulsion, to their target. This proposal investigates how attractive and repulsive signals are received and integrated in neurons to enable axons to find their targets in the brain.