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'FOXP2' ("forkhead box P2") is a gene that is implicated in the development of language skills,^[1] including grammatical competence.

Contents

Introduction

FOXP2 and human disease

Function

Evolution

History

See also

References

External links

Introduction

FOXP2 is a member of the large FOX family of transcription factors. Information from known human mutations and mouse studies suggest that FOXP2 regulates genes involved in the development of tissues such as brain, lung, and gut. The exact identity of the genes FOXP2 regulates is still not known, however.

FOXP2 and human disease

Several cases of developmental verbal dyspraxia in humans have been linked to mutations in the FOXP2 gene^[2]. Individuals have little or no cognitive handicaps but are unable to perform the coordinated movements required for speech. fMRI analysis of these individuals performing silent verb generation and spoken word repetition tasks showed underactivation of Broca's area and the putamen, brain centers thought to be involved in language tasks. Because of this, FOXP2 has been dubbed the "speech and language gene". Scientists have also looked for associations between FOXP2 and autism but so far no clear links have been found^[3].
There is some evidence that the linguistic impairments associated with a mutation of the FOXP2 gene are not simply the result of a fundamental deficit in motor control. For example:

★ the impairments include difficulties in comprehension;

★ brain imaging of affected individuals indicates functional abnormalities in language-related cortical regions, demonstrating that the problems extend beyond the motor system.

Function

FOXP2 is required for proper brain and lung development. Knockout mice with only one functional copy of the FOXP2 gene have significantly reduced vocalizations as pups^[4]. Knockout mice with no functional copies of FOXP2 are runted, display abnormalities in brain regions such as the Purkinje layer, and die 21 days after birth from inadequate lung development^[5].
Initial studies of FOXP2 in zebra finch suggest that FOXP2 may regulate genes involved in neuroplasticity: levels of FOXP2 in the brain significantly change when males are learning or practicing their song but not when they are performing their song for females^[6].

Evolution

The FOXP2 protein sequence is highly conserved. Similar FOXP2 proteins can be found in songbirds, fish, and reptiles such as alligators.^[7] Aside from a polyglutamine tract, human FOXP2 differs from chimp FOXP2 by only two amino acids, mouse FOXP2 by only 3 amino acids, and zebra finch FOXP2 by only 7 amino acids.^[8][9] Some researchers have speculated that the two amino acid differences between chimps and humans led to the evolution of language in humans.^[8] Others, however, have been unable to find a clear association between species with learned vocalizations and similar mutations in FOXP2.^[7] Both human mutations occur in an exon with no known function.

History

The search for the gene was initially started as a result of the investigations into the KE (or K) family. Certain members of this family suffered from an inherited speech and language disorder and living members stretched back three generations. Closer inspection of the family revealed the disorder to be autosomal dominant.
A scan was performed of the genome of the affected and some of the unaffected family members. This initial scan limited the affected region to a spot on chromosome 7, which the team called "SPCH1". Sequencing of this region was done with the aid of bacterial artificial chromosome clones. At this point, another individual was located who had a similar disorder but was unrelated to the family. The genome of this individual was mapped and it was discovered that there was a break in chromosome 7.
Further investigation discovered a point mutation in this chromosome. Sequenced and analysed, this is now referred to as the FOXP2 gene.

See also

★ FOX proteins

★ FOXP1

★ dyspraxia

★ Broca's area

★ Evolution of Homo sapiens

★ Human evolutionary genetics

★ Human Genome Project

★ Chimpanzee genome project

References

1. The SPCH1 region on human 7q31: genomic characterization of the critical interval and localization of translocations associated with speech and language disorder, Lai C, Fisher S, Hurst J, Levy E, Hodgson S, Fox M, Jeremiah S, Povey S, Jamison D, Green E, Vargha-Khadem F, Monaco A, , , Am J Hum Genet, 2000
2. FOXP2 and the neuroanatomy of speech and language, Vargha-Khadem F, Gadian DG, Copp A, Mishkin M, , , Nature Reviews Neuroscience, 2005
3. FOXP2 is not a major susceptibility gene for autism or specific language impairment, Newbury DF, Bonora E, Lamb JA, Fisher SE, Lai CS, Baird G, Jannoun L, Slonims V, Stott CM, Merricks MJ, Bolton PF, Bailey AJ, Monaco AP, , , Am J Hum Genet, 2002
4. Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene, Shu W, Cho JY, Jiang Y, Zhang M, Weisz D, Elder GA, Schmeidler J, De Gasperi R, Sosa MA, Rabidou D, Santucci AC, Perl D, Morrisey E, Buxbaum JD, , , Proc Natl Acad Sci U S A, 2005
5. Foxp2 and Foxp1 cooperatively regulate lung and esophagus development, Shu W, Lu MM, Zhang Y, Tucker PW, Zhou D, Morrisey EE, , , Development, 2007
6. FoxP2 regulation during undirected singing in adult songbirds, Teramitsu I, White SA, , , J Neurosci, 2006
7. FoxP2 in song-learning birds and vocal-learning mammals, Webb DM, Zhang J, , , J Hered., 2005
8. Molecular evolution of FOXP2, a gene involved in speech and language, Enard W, Przeworski M, Fisher S, Lai C, Wiebe V, Kitano T, Monaco A, Pääbo S, , , Nature, 2002
9. Parallel FoxP1 and FoxP2 expression in songbird and human brain predicts functional interaction, Teramitsu I, Kudo LC, London SE, Geschwind DH, White SA, , , J Neurosci., 2004
10. Molecular evolution of FOXP2, a gene involved in speech and language, Enard W, Przeworski M, Fisher S, Lai C, Wiebe V, Kitano T, Monaco A, Pääbo S, , , Nature, 2002
11. FoxP2 in song-learning birds and vocal-learning mammals, Webb DM, Zhang J, , , J Hered., 2005

External links

★ The FOXP2 gene in neurological development at University of Oxford