Brain Advance Access originally published online on July 22, 2003
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Brain, Vol. 126, No. 11, 2455-2462,
November 2003
© 2003 Guarantors of Brain
doi: 10.1093/brain/awg247
FOXP2 expression during brain development coincides with adult sites of pathology in a severe speech and language disorder
1 Neural Development Unit, Institute of Child Health, University College London, London and 2 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
Correspondence to: Dr Simon E. Fisher, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN or Professor Andrew J. Copp, Neural Development Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK E-mail: simon.fisher{at}well.ox.ac.uk or a.copp{at}ich.ucl.ac.uk
Disruption of FOXP2, a gene encoding a forkhead-domain transcription factor, causes a severe developmental disorder of verbal communication, involving profound articulation deficits, accompanied by linguistic and grammatical impairments. Investigation of the neural basis of this disorder has been limited previously to neuroimaging of affected children and adults. The discovery of the gene responsible, FOXP2, offers a unique opportunity to explore the relevant neural mechanisms from a molecular perspective. In the present study, we have determined the detailed spatial and temporal expression pattern of FOXP2 mRNA in the developing brain of mouse and human. We find expression in several structures including the cortical plate, basal ganglia, thalamus, inferior olives and cerebellum. These data support a role for FOXP2 in the development of corticostriatal and olivocerebellar circuits involved in motor control. We find intriguing concordance between regions of early expression and later sites of pathology suggested by neuroimaging. Moreover, the homologous pattern of FOXP2/Foxp2 expression in human and mouse argues for a role for this gene in development of motor-related circuits throughout mammalian species. Overall, this study provides support for the hypothesis that impairments in sequencing of movement and procedural learning might be central to the FOXP2-related speech and language disorder.
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