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Foxp2 helps wiring of neurons in developing brain
Foxp2, a gene involved in speech and language, helps regulate the wiring of neurons in the brain, according to a study led by Sonja C. Vernes and Simon E. Fisher (Wellcome Trust Centre for Human Genetics, Oxford and MPI, Nijmegen). The study was published on July 7th in the open-access journal PLoS Genetics. The researchers identified this functional link by first uncovering the genetic programmes downstream of Foxp2 in developing brain tissue and then analysing its functional effects in neurons.
Foxp2 codes for a regulatory protein that provides a window into intriguing aspects of brain function. In 2001, Simon Fisher and his colleagues discovered that mutations of the human gene cause a rare form of speech and language disorder. The finding triggered a decade of intense research into the human gene and corresponding versions found in other species – for example, it has been shown to affect vocal imitation in songbirds, and learning of rapid movement sequences in mice.
Genetic dimmer switch
In the PLoS Genetics study, the researchers gained insights into the functions of Foxp2 within the developing brain by exploiting its role as a genetic dimmer switch, turning up or down the amount of product made by other genes. In their large-scale screening of embryonic brain tissue, they identified many novel target genes regulated by Foxp2. Remarkably, an excess of these targets were known to be important for connectivity of the central nervous system. The team went on to show that changing Foxp2 levels in neurons impacted on the length and branching of neuronal projections, a key route for modulating the wiring of the developing brain. Interestingly, the genes that control these early processes can also play roles in connectivity at later stages of development and some may even affect plasticity of connections between neurons in the mature brain.
New candidate genes
"Studies like this are crucial for building bridges between genes and complex aspects of brain function" says Simon Fisher, director of MPI's Language and Genetics department. The research was carried out with mouse models, since they can be used to comprehensively analyse genetic networks in a way that remains difficult in the human brain. However, "the current study provides the most thorough characterisation of Foxp2 target pathways to date," he notes. "It offers a number of compelling new candidate genes that could be investigated in people with language problems."
Link to the publication.