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Abstract:
Our unparalleled capacity for complex spoken language is one of the most intriguing aspects of being human. Scientists are pinpointing genes that contribute, mainly by studying disorders involving disturbed language development. My lecture begins with an overview of the state-of-the-art in these gene-mapping efforts. Identification of language-related genes opens up novel research avenues, providing unique molecular windows into key neural pathways. I will illustrate the approach by focusing on the gene FOXP2. Over a decade ago, my colleagues and I discovered that FOXP2 mutations cause problems mastering sequences of co-ordinated mouth movements needed for fluent speech, accompanied by expressive and receptive language impairments. The FOXP2 gene encodes a regulatory protein which modulates expression of other genes. It is evolutionarily ancient, found in similar form in diverse vertebrates, where it helps regulate development and function of corresponding neuronal subpopulations. The FOXP2 protein underwent accelerated change on the human lineage after splitting from the chimpanzee, suggesting that its role(s) may have been modified in our ancestors. Nevertheless, FOXP2 should not be viewed as the mythical "gene for speech", but instead as one piece of a complex puzzle. To investigate FOXP2 function, researchers exploit a range of systems, from neuronal models, mutant mice and songbirds, to humans themselves. For example, using functional genomics in human neuronal-like cells, we identified the CNTNAP2 gene (a member of the neurexin superfamily) as a target directly regulated by FOXP2. Intriguingly, CNTNAP2 is itself associated with common language impairments, has been implicated in language delays of autistic children and may even affect linguistic skills in the general population. High-throughput screens uncovered many other FOXP2 targets, highlighting gene networks involved in neurite outgrowth, axon guidance and synaptic plasticity. Moving to animal models of FOXP2 dysfunction, we have shown that point mutations implicated in human speech deficits yield impaired motor-skill learning in mutant mice. Electrophysiological recordings suggest this is mediated by altered plasticity of Foxp2-expressing networks, particularly in corticostriatal circuits. The final part of my talk considers the future of the field, in light of major developments such as whole genome sequencing and neuroimaging genetics. Overall, this exciting area of research is building the first bridges between genes, neurons, brains, and spoken language.
