Emilia Stasiak

A great deal of scientific research is driven by a very fundamental question: What makes us human? And what are the properties of the human brain that make these talents possible? One challenge facing scientists is that answering these questions often requires the use of nonhuman animals as subjects. In fact, animal models have even proved essential when it comes to studying uniquely human talents, such as language.

In 2001 Cecilia S. L. Lai and colleagues at the University of Oxford identified FOXP2 as the first gene specifically involved in speech and language development in humans. The gene was discovered when researchers began studying members of a family that exhibited severe language deficits: they struggled to speak in grammatically correct sentences and often failed to comprehend the language of others, although they demonstrated no other cognitive handicaps. A genetic analysis of the family linked these severe linguistic deficits to a mutation in the FOXP2 gene. Interestingly, the FOXP2 gene is highly conserved among vertebrates, including humans, songbirds, bats and rodents, perhaps indicating a shared function. Experimental evidence from a variety of animals suggests a general role in communication for FOXP2. For instance, mice that lack the gene produce abnormal ultrasonic vocalizations, while the expression of the gene changes in the brains of songbirds during vocal learning.

Mice have been especially useful models in elucidating the role of FOXP2 in communication and fine motor development. While this might seem paradoxical (rodents don’t talk, so how can they teach us about speech?) mice have several important advantages. As mammals, they share many aspects of anatomy with humans and their entire genome has been sequenced. Multiple experimental techniques are easily employed with mice, including various genetic manipulations and behavioral assays. The recent discovery that male mice produce ultrasonic songs only adds to their attractiveness as a behaviorally relevant model for vocal communication.

Polly Campbell and her colleagues at the University of Florida sought to extend the FOXP2 research by systematically describing the neural distribution of FOXP2 protein in laboratory mice, deer mice, and two species of Central American singing mice. The researchers chose to examine singing mice because their complex vocalizations require precise coordination of facial muscles, presenting the possibility of unique expression patterns of FOXP2 in regions involved in fine motor control. Campbell and colleagues also hoped to use their data to develop a more general model for the FOXP2 pathways that are common in all mammals, and not just in species, such as people and songbirds, that produce complex vocalizations.

Although the authors expected to find differences in FOXP2 expression in singing mice relative to the two other mouse species, they were surprised to see that the pattern of expression in the brain was generally very similar in all four species. Brain areas abundant with FOXP2 protein included the cerebellum and inferior olivary complex (implicated in motor preparation and timing of motor output), the limbic cortex (involved in motivational regulation and assessment of sensory input), and parts of the olfactory system, which is integral to social interactions and emotional responses in most rodents. Interestingly, the distribution of FOXP2 protein in the olfactory system also suggests involvement in assessing the emotional content of sensory input. Strong localization of expression to these deep brain structures, together with the comparative lack of expression in areas responsible for the control of facial muscles and the larynx, indicate that FOXP2 is more involved in motivational and integrative pathways than in direct control of fine motor output.