Conservation and diversity of Foxp2 expression in muroid rodents: Functional implications

Abstract

FOXP2, the first gene causally linked to a human language disorder, is implicated in song acquisition, production and perception in oscine songbirds, the evolution of speech and language in hominids and the evolution of echolocation in bats. Despite the evident relevance of Foxp2 to vertebrate acoustic communication, a comprehensive description of neural expression patterns is currently lacking in mammals. Here we use immunocytochemistry to systematically describe the neural distribution of Foxp2 protein in four species of muroid rodents: Scotinomys teguina and S. xerampelinus (‘singing mice’), the deer mouse, Peromyscus maniculatus, and the lab mouse, Mus musculus. While expression patterns were generally highly conserved across brain regions, we identified subtle but consistent interspecific differences in Foxp2 distribution, most notably in the medial amygdala and nucleus accumbens, and in layer V cortex throughout the brain. Throughout the brain, Foxp2 was highly enriched in areas involved in modulation of fine motor output (striatum, mesolimbic dopamine circuit, olivocerebellar system), and in multimodal sensory processing and sensorimotor integration (thalamus, cortex). We propose a generalized model for Foxp2-modulated pathways in the adult brain including, but not limited to, fine motor production and auditory perception.

Neuromolecular responses to social challenge: Common mechanisms across mouse, stickleback fish, and honey bee

“…Brains were dissected and RNA was extracted and quantified following standard procedures. Poly-A RNA was enriched from total RNA, using Dynabeads Oligo(dT) 25 analyses identified one mouse control sample and two bee control samples as outliers, and these samples were excluded from further analyses (final sample sizes were 3/2, 3/3, 6/4 experimental/ control for mouse, stickleback, and honey bee, respectively). For each species, we filtered out genes with extremely low expression levels.…”

“…Transcription factors (TFs) regulate large networks of genes and thus are predicted to play an important role in modulating complex phenotypes like social behavior (7,23,25,26). The term sequence-specific DNA binding transcription factor activity was enriched in mouse (Dataset S1 and Fig.…”

What can mice tell us about Foxp2 function?

“…Given that expression persists into adulthood [19 ], it seems likely that the protein also has regulatory functions in postnatal animals, perhaps throughout adult life. In songbirds, FoxP2 knockdown in striatal Area X of juvenile zebra finches results in inaccurate imitation of the song of a tutor [51].…”

Convergent repression of Foxp2 3′UTR by miR-9 and miR-132 in embryonic mouse neocortex: implications for radial migration of neurons

“…Two functional copies of this transcription factor are required for the proper development of speech and language in humans (Fisher and Scharff, 2009;Lai et al, 2001), and two amino acid changes during human evolution might have tuned specific speechrelevant properties of corticobasal ganglia circuits (Enard, 2011;Enard et al, 2009;Enard et al, 2002). In the embryonic mouse, neocortex Foxp2 starts its expression in postmigratory neurons, and in the postnatal cortex it is restricted to projections neurons of layers V-VI (Ferland et al, 2003;Takahashi et al, 2003;Campbell et al, 2009;Hisaoka et al, 2010;Reimers-Kipping et al, 2011). Remarkably, detectable levels of Foxp2 mRNA have been reported in embryonic germinal zones of the mouse telencephalon -but not Foxp2 protein (Ferland et al, 2003;Takahashi et al, 2003).…”