Expression of Foxp2, a gene involved in speech and language, in the developing and adult striatum

Abstract

Many members of the forkhead/winged helix transcriptional factors are known to be regulators of embryogenesis. Mutations of the Fox gene family have been implicated in a range of human developmental disorders. Foxp2, a member of the Fox gene family, has recently been identified as the first gene that is linked to an inherited form of language and speech disorder. To elucidate the anatomical basis of language processing in the brain, we have examined the expression pattern of Foxp2 gene and its homologous gene, Foxp1, in the rat brain through development. Expression of Foxp2 mRNA was detected in the ventral telencephalon as early as embryonic day 13. Foxp2 mRNA was expressed primarily in differentiated cells of the lateral ganglionic eminence (striatal primordium). Of particular interest was that the developmental expression of Foxp2 followed a compartmental order in the striatum. Patches containing high levels of Foxp2 were aligned with patches enriched in mu-opoid receptor, a marker for striosomal cells, in the striatum through postnatal development. Conversely, Foxp2-positive patches were devoid of calbindin-D28k, a maker for striatal matrix cells. Therefore, Foxp2 was preferentially expressed in striosomal compartment in the striatum during development. In the mature striatum, Foxp2 expression was maintained in striosomes, although its expression level was reduced. In contrast to Foxp2, Foxp1 was expressed in both the striosomal and matrix compartments in the striatum through development. The striatum is known to be involved in the process of procedural memory, and mutation of Foxp2 results in neurological disorders of language and speech. Given the preferential expression of Foxp2 in the striosomal compartment, the striatum, particularly the striosomal system, may participate in neural information processing for language and speech. Our suggestion is consistent with the declarative/procedural model proposed by Ullman and colleagues (Ullman et al. [1997] J. Cogn. Neurosci. 9:266-276; Ullman [2001] Nat. Rev. Neurosci. 2:717-726), in which the procedural memory-dependent mental grammar is rooted in the basal ganglia and the frontal cortex and the declarative memory-dependent mental lexicon is rooted in the temporal lobe.

Altered proliferative ability of neuronal progenitors in PlexinA1 mutant mice

“…To assess whether projection neuron numbers were also affected within the striatum, we immunostained coronal sections from PlexinA1 −/− mice and PlexinA1 +/ + littermates at E14.5 and E18.5 (n = 3 per age for each genotype) for the transcription factor Forkhead box protein P2 (FOXP2), a marker of developing striatal projection neurons (Takahashi et al, 2003). Counts of labeled cells throughout the rostrocaudal extent of the striatum showed a significant reduction in mutants compared with control littermates at E14.5 (medial levels PlexinA1 +/ + 711.21 ± 4.53 cells/10 5 µm 2 , PlexinA1 −/− 548.96 ± 4.57 cells/10 5 µm 2 ; P  < 0.00049) and at E18.5 ( PlexinA1 +/ + 840.45 ± 5.44 cells/10 5 µm 2 , PlexinA1 −/− 658.75 ± 5.48 cells/10 5 µm 2 ; P  < 0.00054; Fig.…”

“…ab16046, RRID: AB_210710) raised against a synthetic peptide in the C‐terminus of human FOXP2 was previously shown to immunolabel striatal projection neurons in the developing mouse forebrain (Takahashi et al, 2003; Hernandez‐Miranda et al, 2011). …”

Identification of a developmentally regulated striatum-enriched zinc-finger gene, Nolz-1 , in the mammalian brain

“…The isotope and nonisotope methods of in situ hybridization were performed as described (11,18 (19,20).…”

Ultrasonic vocalization impairment of Foxp2 (R552H) knockin mice related to speech-language disorder and abnormality of Purkinje cells

“…The structure of FoxP2 is highly conserved during evolution as well (12), because the human FOXP2 protein differs at only 2 aa compared with its mouse homologue, along with one glutamine from the human protein that is absent in the polyQ tract in mouse Foxp2 (12). Human FOXP2 and mouse Foxp2 show quite similar expression patterns in the developing brain, with expression detected in the cortical plate, basal ganglia, thalamus, and inferior olive (13,14).…”

“…The structure of FoxP2 is highly conserved during evolution as well (12), because the human FOXP2 protein differs at only 2 aa compared with its mouse homologue, along with one glutamine from the human protein that is absent in the polyQ tract in mouse Foxp2 (12). Human FOXP2 and mouse Foxp2 show quite similar expression patterns in the developing brain, with expression detected in the cortical plate, basal ganglia, thalamus, and inferior olive (13,14).Infant rodents emit ultrasonic vocalizations (USVs), whistle-like sounds with frequencies between 40 kHz and 100 kHz, when isolated from the mother and littermates (15). These signals play an important communicative role in mother-offspring interactions because they elicit prompt responses from the dam concerning caregiving behaviors (15).…”