The Role Of The Gtf2i Gene Family In Behaviour And Williams Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$629,396.00
Summary
Williams Syndrome (WS) is a complex neurodevelopmental disorder in humans caused by a deletion of 21 genes on chromosome 7. This results in a reduced IQ and marked visuospatial deficiencies. However, unlike other forms of mental retardation, some important cognitive abilities are completely normal. WS patients show normal development of linguistic abilities and anecdotal evidence suggests they possess an above average musical ability. In addition, these individuals also possess a characteristic ....Williams Syndrome (WS) is a complex neurodevelopmental disorder in humans caused by a deletion of 21 genes on chromosome 7. This results in a reduced IQ and marked visuospatial deficiencies. However, unlike other forms of mental retardation, some important cognitive abilities are completely normal. WS patients show normal development of linguistic abilities and anecdotal evidence suggests they possess an above average musical ability. In addition, these individuals also possess a characteristic overfriendly, gregarious personality with little inhibition towards strangers. Such a characteristic cognitive and behavioral profile in a genetic disorder has provided convincing evidence that genes play a role in specifying cognitive abilities and behavior. This interesting syndrome gives us an insight into the perplexing debate of Nature vs Nurture. It also provides a unique and invaluable opportunity to dissect the role of certain genes in complex neurodevelopmental pathways that result in cognition and behavior. Recently, patients with smaller (atypical) deletions of genes in the WS region have been described. These patients do not display the full 'classical' range of WS characteristics. The identification of which genes are deleted in these patients suggests that two genes in particular, GTF2IRD1 and GTF2I, are involved in visuospatial abilities, sociability and specific anxieties and phobias. Our laboratory was the first to identify proteins encoded by GTF2IRD1, known as MusTRDs, that act for the most part to suppress gene expression. Furthermore, our laboratory has been studying a mouse model in which the Gtf2ird1 gene has been deleted, similar to the situation in WS, and have found that the mice are more 'social' and exploratory. In this project, we want to determine if other behavioural features of WS are contributed to by this gene and-or its related gene, Gtf2i, and to characterize the role that these genes play in neuronal cell function.Read moreRead less
Genetic Cues Responsible For Interneuron Migration And Layering In The Neocortex
Funder
National Health and Medical Research Council
Funding Amount
$650,250.00
Summary
Understanding how the brain is assembled, and the genes that drive this process, will provide insights into two exciting areas of current neuroscience. First, it will clarify how we differ from other species, and illuminate the evolutionary concepts underscoring functional specialization. Secondly, there are sound health-related reasons to study brain development. Proper brain function requires the proper assembly of neurons and the establishment of circuitry. Defective generation of neurons in ....Understanding how the brain is assembled, and the genes that drive this process, will provide insights into two exciting areas of current neuroscience. First, it will clarify how we differ from other species, and illuminate the evolutionary concepts underscoring functional specialization. Secondly, there are sound health-related reasons to study brain development. Proper brain function requires the proper assembly of neurons and the establishment of circuitry. Defective generation of neurons in sufficient numbers, or impediments to neuron migration to proper destinations are certain recipes for neurological disorders, including epilepsy and mental retardation. In this application, we will study how neurons are assembled in the cortex. We will focus on a subpopulation known as interneurons that are vital for toning down electrical discharges from excitatory neurons. We will investigate how these neurons are able to migrate long distances to settle into defined layers of the cortex. Mutant mice with deleted genes have a defect in this process and the aim of this project will be to study the precise mode of action for some of these genes.Read moreRead less