What can mice tell us about Foxp2 function?

Abstract

Disruptions of the FOXP2 gene cause a rare speech and language disorder, a discovery that has opened up novel avenues for investigating the relevant neural pathways. FOXP2 shows remarkably high conservation of sequence and neural expression in diverse vertebrates, suggesting that studies in other species are useful in elucidating its functions. Here we describe how investigations of mice that carry disruptions of Foxp2 provide insights at multiple levels: molecules, cells, circuits and behaviour. Work thus far has implicated the gene in key processes including neurite outgrowth, synaptic plasticity, sensorimotor integration and motor-skill learning.

A Molecular Genetic Perspective on Speech and Language

“…A proper discussion of the many findings from this research area is beyond the scope of this chapter. The interested reader is referred to recent reviews (French & Fisher, 2014;Wohlgemuth, Adam, & Scharff, 2014). Here, a sample of the work is provided, focusing on two of the most extensively studied model systems: mice and (briefly) birds (Fisher & Scharff, 2009).…”

Insights into the Genetic Foundations of Human Communication

“…Unfortunately, the rodent species which are the mainstay of molecular genetic research exhibit very limited vocal learning abilities, although they can still be used to study basic processes such as auditory-motor association learning (Kurt et al 2012;French and Fisher 2014). Certain language-relevant behaviors have been investigated in species such as primates, dolphins, elephants, seals and dogs, including the learning of vocalizations and of vocal labels, and the use of turn taking in interaction (Fedurek and Slocombe 2011;Reichmuth and Casey 2014;Griebel and Oller 2012;Takahashi et al 2013;Janik 2014;Stoeger and Manger 2014).…”

“…The role of FOXP2 in the development of neural circuitry has been further investigated using several mutant mouse lines (Fisher and Scharff 2009;French and Fisher 2014). Mice lacking functional Foxp2 (the rodent ortholog of human FOXP2) have developmental delays and severe motor impairments, dying at 3-4 weeks after birth (French and Fisher 2014).…”

“…Mice lacking functional Foxp2 (the rodent ortholog of human FOXP2) have developmental delays and severe motor impairments, dying at 3-4 weeks after birth (French and Fisher 2014). Mice with one functional copy of Foxp2 are normal or show mild developmental delays, depending on the genomic background, but in-depth investigations have uncovered deficits which may help explain the speech impairments observed in patients with FOXP2-related CAS.…”

“…Several studies have reported on effects of Foxp2 disruption on the ultrasonic vocalizations of mouse pups, but these vocal behaviors are not a good model for human speech and such findings should be viewed with caution (see Fisher and Scharff 2009;French and Fisher 2014 for more extensive discussion). More relevant to speech are investigations of zebra finches, which have addressed potential contributions of FoxP2 (the songbird ortholog of human FOXP2) to vocal learning (Wohlgemuth et al 2014).…”