Editing FOXP2 (section)

== Structure and function ==
[[File:Foxp2, ISH, E13.5 mouse, cerebellum-hindbrain.jpg|thumbnail|left|upright=.85|[http://developingmouse.brain-map.org/data/Foxp2/100092348.html?ispopup=true Foxp2] is expressed in the developing cerebellum and the hindbrain of the embryonic day 13.5 mouse. [[Allen Brain Atlas]]es]]

As a [[FOX protein]], FOXP2 contains a forkhead-box domain. In addition, it contains a [[polyglutamine tract]], a [[zinc finger]] and a [[leucine zipper]]. The protein attaches to the DNA of other proteins and controls their activity through the forkhead-box domain. Only a few targeted genes have been identified, however researchers believe that there could be up to hundreds of other genes targeted by the FOXP2 gene. The forkhead box P2 protein is active in the brain and other tissues before and after birth, and many studies show that it is paramount for the growth of nerve cells and transmission between them. The FOXP2 gene is also involved in synaptic plasticity, making it imperative for learning and memory.<ref name = "GHR_FOXP2">{{cite web | title = FOXP2 Gene | work = Genetics Home Reference | publisher = U.S. National Library of Medicine, National Institutes of Health | date = September 2016 | url = https://ghr.nlm.nih.gov/gene/FOXP2 }}</ref>

''FOXP2'' is required for proper brain and lung development. [[Knockout mouse|Knockout mice]] with only one functional copy of the ''FOXP2'' gene have significantly reduced vocalizations as pups.<ref name="Shu_2005">{{cite journal | vauthors = 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 | title = Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 27 | pages = 9643–8 | date = July 2005 | pmid = 15983371 | pmc = 1160518 | doi = 10.1073/pnas.0503739102 | doi-access = free | bibcode = 2005PNAS..102.9643S }}</ref> Knockout mice with no functional copies of ''FOXP2'' are runted, display abnormalities in brain regions such as the [[Purkinje layer]], and die an average of 21 days after birth from inadequate lung development.<ref name="Shu_2007">{{cite journal | vauthors = Shu W, Lu MM, Zhang Y, Tucker PW, Zhou D, Morrisey EE | title = Foxp2 and Foxp1 cooperatively regulate lung and esophagus development | journal = Development | volume = 134 | issue = 10 | pages = 1991–2000 | date = May 2007 | pmid = 17428829 | doi = 10.1242/dev.02846 | s2cid = 22896384 | doi-access =  }}</ref>

''FOXP2'' is expressed in many areas of the brain,<ref name="Enard_2002">{{cite journal | vauthors = Enard W, Przeworski M, Fisher SE, Lai CS, Wiebe V, Kitano T, Monaco AP, Pääbo S | title = Molecular evolution of FOXP2, a gene involved in speech and language | journal = Nature | volume = 418 | issue = 6900 | pages = 869–72 | date = August 2002 | pmid = 12192408 | doi = 10.1038/nature01025 | url = http://ruccs.rutgers.edu/~karin/550.READINGS/EVOLUTION/Enard2002.pdf | url-status = dead | hdl-access = free | hdl = 11858/00-001M-0000-0012-CB89-A | s2cid = 4416233 | bibcode = 2002Natur.418..869E | archive-url = https://web.archive.org/web/20060830073732/http://ruccs.rutgers.edu/~karin/550.READINGS/EVOLUTION/Enard2002.pdf | archive-date = 30 August 2006 }}</ref> including the [[basal ganglia]] and inferior [[frontal cortex]], where it is essential for brain maturation and speech and language development.<ref name="Spiteri_2007">{{cite journal | vauthors = Spiteri E, Konopka G, Coppola G, Bomar J, Oldham M, Ou J, Vernes SC, Fisher SE, Ren B, Geschwind DH | title = Identification of the transcriptional targets of FOXP2, a gene linked to speech and language, in developing human brain | journal = American Journal of Human Genetics | volume = 81 | issue = 6 | pages = 1144–57 | date = December 2007 | pmid = 17999357 | pmc = 2276350 | doi = 10.1086/522237 }}</ref> In mice, the gene was found to be twice as highly expressed in male pups than female pups, which correlated with an almost double increase in the number of vocalisations the male pups made when separated from mothers. Conversely, in human children aged 4–5, the gene was found to be 30% more expressed in the [[Broca's area]]s of female children. The researchers suggested that the gene is more active in "the more communicative sex".<ref>{{Cite journal | vauthors = Balter M | title = 'Language Gene' More Active in Young Girls Than Boy | journal = Science | date = February 2013 | page = 360 |url=https://www.science.org/content/article/language-gene-more-active-young-girls-boys }}</ref><ref>{{cite journal | vauthors = Bowers JM, Perez-Pouchoulen M, Edwards NS, McCarthy MM | title = Foxp2 mediates sex differences in ultrasonic vocalization by rat pups and directs order of maternal retrieval | journal = The Journal of Neuroscience | volume = 33 | issue = 8 | pages = 3276–83 | date = February 2013 | pmid = 23426656 | pmc = 3727442 | doi = 10.1523/JNEUROSCI.0425-12.2013 }}</ref>

The expression of ''FOXP2'' is subject to [[post-transcriptional regulation]], particularly [[microRNA]] (miRNA), causing the repression of the FOXP2 [[3' untranslated region]].<ref name="Clovis_2012">{{cite journal | vauthors = Clovis YM, Enard W, Marinaro F, Huttner WB, De Pietri Tonelli D | title = Convergent repression of Foxp2 3'UTR by miR-9 and miR-132 in embryonic mouse neocortex: implications for radial migration of neurons | journal = Development | volume = 139 | issue = 18 | pages = 3332–42 | date = September 2012 | pmid = 22874921 | doi = 10.1242/dev.078063 | doi-access = free }}</ref>

Three amino acid substitutions distinguish the human ''FOXP2'' protein from that found in mice, while two amino acid substitutions distinguish the human ''FOXP2'' protein from that found in chimpanzees,<ref name="Enard_2002" /> but only one of these changes is unique to humans.<ref name="Shu_2007" /> Evidence from genetically manipulated mice<ref name="Enard_2009">{{cite journal | vauthors = Enard W, Gehre S, Hammerschmidt K, Hölter SM, Blass T, Somel M, Brückner MK, Schreiweis C, Winter C, Sohr R, Becker L, Wiebe V, Nickel B, Giger T, Müller U, Groszer M, Adler T, Aguilar A, Bolle I, Calzada-Wack J, Dalke C, Ehrhardt N, Favor J, Fuchs H, Gailus-Durner V, Hans W, Hölzlwimmer G, Javaheri A, Kalaydjiev S, Kallnik M, Kling E, Kunder S, Mossbrugger I, Naton B, Racz I, Rathkolb B, Rozman J, Schrewe A, Busch DH, Graw J, Ivandic B, Klingenspor M, Klopstock T, Ollert M, Quintanilla-Martinez L, Schulz H, Wolf E, Wurst W, Zimmer A, Fisher SE, Morgenstern R, Arendt T, de Angelis MH, Fischer J, Schwarz J, Pääbo S | title = A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice | journal = Cell | volume = 137 | issue = 5 | pages = 961–71 | date = May 2009 | pmid = 19490899 | doi = 10.1016/j.cell.2009.03.041 | hdl-access = free | s2cid = 667723 | hdl = 11858/00-001M-0000-000F-F8C5-2 }}</ref> and human neuronal cell models<ref name="Konopka_2009">{{cite journal | vauthors = Konopka G, Bomar JM, Winden K, Coppola G, Jonsson ZO, Gao F, Peng S, Preuss TM, Wohlschlegel JA, Geschwind DH | title = Human-specific transcriptional regulation of CNS development genes by FOXP2 | journal = Nature | volume = 462 | issue = 7270 | pages = 213–7 | date = November 2009 | pmid = 19907493 | pmc = 2778075 | doi = 10.1038/nature08549 | bibcode = 2009Natur.462..213K}}
*{{cite press release |date=November 12, 2009 |title=Why Can't Chimps Speak? Key Differences In How Human And Chimp Versions Of FOXP2 Gene Work |website=ScienceDaily |url=https://www.sciencedaily.com/releases/2009/11/091111130942.htm}}</ref> suggests that these changes affect the neural functions of ''FOXP2''.