Decoding Conserved Mechanisms That Control Neuronal Migration
Funder
National Health and Medical Research Council
Funding Amount
$526,950.00
Summary
During brain development, nerve cells interact with each other and their surrounding environment through a forest of molecules that are essential for precise cellular communication. Deficient signaling between these molecules causes defects in development and leads to disease. By employing genetic and biochemical approaches we propose to identify new mechanisms through which the brain develops, to better understand how brain diseases such as epilepsy and schizophrenia occur.
The Role Of The Ras Signalling Molecule, C3G, In The Interaction Of Neural Precursor Cells And Their Environment
Funder
National Health and Medical Research Council
Funding Amount
$319,446.00
Summary
Developmental brain disorders affect 1-3% of the population. The mental retardation disease spectrum includes neuronal migration disorders and neural precursor proliferation disorders. We propose to study a molecular mechanism regulating neuronal migration, survival and proliferation. We have identified a protein, C3G, which is essential for three aspects of nervous system development: (A) C3G limits neural precursor cell proliferation. (B) C3G is essential for neuronal survival. (C) C3G is cruc ....Developmental brain disorders affect 1-3% of the population. The mental retardation disease spectrum includes neuronal migration disorders and neural precursor proliferation disorders. We propose to study a molecular mechanism regulating neuronal migration, survival and proliferation. We have identified a protein, C3G, which is essential for three aspects of nervous system development: (A) C3G limits neural precursor cell proliferation. (B) C3G is essential for neuronal survival. (C) C3G is crucial for neuronal migration. C3G acts in a cascade of proteins, known as the Ras signalling pathway, which transmits signals from the extracellular environment into the cell nucleus to elicit appropriate responses of the cell to cues from the outside. We will identify proteins that, together with C3G, affect the important processes of neural precursor proliferation, and neuron survival and migration. This project will fully characterise a key regulatory mechanism of cellular processes crucial to the development of normal intelligence.Read moreRead less
Sialyltransferase In The Bipolar And Schizophrenic Brain: Examining The Role Of A Novel Generalised Susceptibility Gene
Funder
National Health and Medical Research Council
Funding Amount
$512,627.00
Summary
Bipolar disorder and schizophrenia are two major psychiatric conditions affecting over 800,000 Australians. We have identified a new gene which contributes to increased risk to developing both bipolar disorder and schizophrenia. We will investigate the function of this gene in normal brain development, and how this function is disrupted in individuals with bipolar disorder and schizophrenia. Understanding the biological cause will help us define better treatments for these severe mental illnesse ....Bipolar disorder and schizophrenia are two major psychiatric conditions affecting over 800,000 Australians. We have identified a new gene which contributes to increased risk to developing both bipolar disorder and schizophrenia. We will investigate the function of this gene in normal brain development, and how this function is disrupted in individuals with bipolar disorder and schizophrenia. Understanding the biological cause will help us define better treatments for these severe mental illnesses.Read moreRead less
Neurons in the two hemispheres of the brain make connections with each other via a large fibre tract called the corpus callosum. In over fifty different human congenital syndromes the corpus callosum fails to form properly. Such syndromes, which include Aicardi syndrome, Andermann syndrome, Shapiro syndrome and Acrocallosal syndrome, can result in mental retardation, seizures, lack of motor coordination and ocular abnormalities in children. Our data on both mouse and human brain development show ....Neurons in the two hemispheres of the brain make connections with each other via a large fibre tract called the corpus callosum. In over fifty different human congenital syndromes the corpus callosum fails to form properly. Such syndromes, which include Aicardi syndrome, Andermann syndrome, Shapiro syndrome and Acrocallosal syndrome, can result in mental retardation, seizures, lack of motor coordination and ocular abnormalities in children. Our data on both mouse and human brain development show that the mouse is an excellent model system for understanding how the brain becomes wired up during development and what may go wrong in these disorders. Here we investigate the role of a family of genes called nuclear factor one (Nfi) genes in brain development. When mutated in mice, members of this gene family, principally Nfia and Nfib, cause severe malformations of the brain. The phenotype inlcudes a failure to form some midline glial populations, the expansion of the cingulate cortex and loss of the corpus callosum. The propoer formation of midline glial populations and the cingulate cortex are essential to callosal fomration and correct brain wiring. Defects in brain wiring in the cingulate cortex during development may underlie disorders such as schizophrenia, bipolar disorder and depression. In this project we will address the mechanism of function underlying the control of brain development by the Nfi genes. The expected outcomes of this research are to identify new mechanisms and genetic pathways critical to the formation of connections between the two sides of the brain and proper formation of the cingulate cortex. These results will improve our understanding of how the brain forms and what mechanisms may be disrupted during development that result in neurological and cognitive deficits in children and adults.Read moreRead less