Presentations

Abstract

The ability to use language is a uniquely human trait involving one of the most complex and poorly understood biological processes. This is particularly true when considering the encoding of human language at the molecular level. Disorders of speech and language are highly heritable and widely prevalent in the general population. Approximately 7% of school age children display specific language impairment (SLI) and language deficiencies are known to feature in a range of common neurodevelopmental disorders such as autism spectrum disorders. The first direct insights into the molecular basis of language were given by the identification of the FOXP2 gene. Mutations in this gene were shown to be causative of a rare speech and language disorder in a large pedigree. Since then, a number of FOXP2 disruptions in unrelated patients displaying a similar phenotype have been reported. However FOXP2 remains the only known monogenic cause of language disorder and little progress has been made via traditional genetic approaches to understanding the molecular basis of language and language impairment. Given that FOXP2 acts as a transcription factor to regulate target gene expression, we hypothesized that understanding the downstream regulatory pathways would give insight into the molecular basis of normal language development and language disorder. We have identified gene networks regulated by FOXP2 that have been implicated in language development and demonstrated that new candidates for involvement in common language disorders can be found by identifying genes that act in these pathways. Our recent findings modeling Foxp2 pathways in the brain, suggest that neuronal connectivity and circuit formation is disturbed in particular types of language disorder due to neurite outgrowth defects during development. We are currently studying how effects on this and other FOXP2 related pathways that we have identified (including Wnt signalling and non-coding RNA pathways) are involved in neural circuit formation and language development, and investigating genetic risk factors from these pathways in patients via genome based screening studies. This novel approach will help us to understand the fundamental neurodevelopmental basis of language and pinpoint genetic risk factors for language impairments.

Abstract

The ability to use language is a uniquely human trait involving one of the most complex and poorly understood biological processes. This is particularly true when considering the encoding of human language at the molecular level. Disorders of speech and language are highly heritable and widely prevalent in the general population. Approximately 7% of school age children display specific language impairment (SLI) and language deficiencies are known to feature in a range of common neurodevelopmental disorders such as autism spectrum disorders. The first direct insights into the molecular basis of language were given by the identification of the FOXP2 gene. Mutations in this gene were shown to be causative of a rare speech and language disorder in a large pedigree. Since then, a number of FOXP2 disruptions in unrelated patients displaying a similar phenotype have been reported. However FOXP2 remains the only known monogenic cause of language disorder and little progress has been made via traditional genetic approaches to understanding the molecular basis of language and language impairment. Given that FOXP2 acts as a transcription factor to regulate target gene expression, we hypothesized that understanding the downstream regulatory pathways would give insight into the molecular basis of normal language development and language disorder. We have identified gene networks regulated by FOXP2 that have been implicated in language development and demonstrated that new candidates for involvement in common language disorders can be found by identifying genes that act in these pathways. Our recent findings modeling Foxp2 pathways in the brain, suggest that neuronal connectivity and circuit formation is disturbed in particular types of language disorder due to neurite outgrowth defects during development. We are currently studying how effects on this and other FOXP2 related pathways that we have identified (including Wnt signalling and non-coding RNA pathways) are involved in neural circuit formation and language development, and investigating genetic risk factors from these pathways in patients via genome based screening studies. This novel approach will help us to understand the fundamental neurodevelopmental basis of language and pinpoint genetic risk factors for language impairments.