Characterization of Foxp2 and Foxp1 mRNA and protein in the developing and mature brain

Abstract

Foxp2 and Foxp1 are recently identified members of the Fox family of winged-helix/forkhead transcription factor genes. A recent study has found that mutations in human FOXP2 produce a severe language disorder. Since Foxp2 appears to be important in language, we wanted to explore the expression of this gene and a homologous gene, Foxp1, in the developing brain. In the present study, we investigated the time course and localization of Foxp2 and Foxp1 mRNA and protein expression in the developing and adult mouse using in situ hybridization and immunohistochemistry. Foxp2 and Foxp1 are expressed as early as E12.5 and persist into adulthood. Foxp2 and Foxp1 were most highly expressed in the developing and mature basal ganglia. Expression of Foxp2 was also observed in the cerebral cortex (layer 6), cerebellum (Purkinje neurons), and thalamus. Foxp1 expression was observed in the cerebral cortex (layers 3-5), hippocampus (CA1), and thalamus. Very little ventricular zone expression was observed for Foxp2 and Foxp1 and the expression of both of these genes occurred following neuronal migration, suggesting a role for these genes in postmigratory neuronal differentiation. Furthermore, we demonstrated the expression of FOXP2 in human fetal brain by RT-PCR, in the perisylvian area of the left and right cerebral hemispheres, as well as in the frontal and occipital cortices. Overall, the widespread expression of Foxp2 in the developing brain makes it difficult to draw specific conclusions about which areas of Foxp2 expression are critical to human language function.

The hyh mutation uncovers roles for αSnap in apical protein localization and control of neural cell fate

“…Similarly, immunoreactivity to Foxp2, which marks early-born neurons in layer VI (ref. 6), was greater, both in density of Foxp2-positive cells in layer VI and in the proportion of the cortical thickness containing Foxp2-immunoreactive neurons . SNARE complex containing syntaxin1A-CFP and synaptobrevin-YFP was incubated with αSnap, followed by addition of NSF to initiate SNARE complex disassembly.…”

Shining a light on CNTNAP2: complex functions to complex disorders

“…16 FOXP1 and FOXP2 show highly overlapping expression patterns and can interact to co-regulate gene expression. [57][58][59][60] A single autistic proband was recently identified carrying mutations in both FOXP1 and CNTNAP2, suggesting a potential link between FOXP1-CNTNAP2 and ASD. 16 This discovery is intriguing given that both FOXP1 and CNTNAP2 mutations have been identified in patients with mild-to-moderate ID, in the presence or absence of autistic features.…”

Insights into the Genetic Foundations of Human Communication

“…Two recentlydiscovered syndromes are caused by haploinsufficiency of transcription factors that are known to directly interact with FOXP2 (Li et al 2004;Sakai et al 2011;Deriziotis et al 2014). One syndrome results from mutations of FOXP1, a paralog of FOXP2 which shows partially overlapping expression in brain regions including the striatum (Ferland et al 2003). The other syndrome results from mutations in TBR1, which is involved in cortical development and is co-expressed with FOXP2 in layer 6 of the cortex (Hevner et al 2001;Willsey et al 2013).…”

“…Additional studies with mutant mice have highlighted deficits in the processing and integration of auditory information (Kurt et al 2009;Kurt et al 2012). In both humans and mice, FOXP2 is expressed in brain regions including the striatum, cerebellum, thalamus and cortex (Ferland et al 2003;Lai et al 2003;Fisher and Scharff 2009). The profile of language impairments observed in individuals with FOXP2 disruptions may represent a compound disorder resulting from reduction in levels of this transcription factor in multiple brain areas involved in speech and language.…”

“…The expression pattern of this gene is broadly conserved in vertebrates, although it remains possible that there may have been subtle alterations in our lineage (Lai et al 2003;Ferland et al 2003;Teramitsu et al 2004). It is highly likely that there are differences in sets of downstream targets in different species, and that such changes may have been influential in driving evolutionary differences in hominin neurodevelopment, but the crucial changes with regard to language have not yet been clearly identified (Nelson et al 2013;Konopka et al 2009).…”