Editing FOXP2 (section)

== In other animals ==

=== <span id="Chimpanzees compared with humans"></span>Chimpanzees ===
In chimpanzees, FOXP2 differs from the human version by two amino acids.<ref>{{Cite journal | vauthors = Smith K |date=2009-11-11|title=Evolution of a single gene linked to language|journal=Nature|doi=10.1038/news.2009.1079|issn=1744-7933}}</ref> A study in Germany sequenced FOXP2's complementary DNA in chimps and other species to compare it with human complementary DNA in order to find the specific changes in the sequence.<ref name="Enard_2002" /> FOXP2 was found to be functionally different in humans compared to chimps. Since FOXP2 was also found to have an effect on other genes, its effects on other genes is also being studied.<ref>{{Cite news|date=2009-11-11|title=Why can't chimps talk? It's more than just genes|work=Reuters|url=https://www.reuters.com/article/us-humans-speech-idUSTRE5AA3J920091111|access-date=2019-02-21}}</ref> Researchers deduced that there could also be further clinical applications in the direction of these studies in regards to illnesses that show effects on human language ability.<ref name="Konopka_2009" />

=== Mice ===
In a mouse ''FOXP2'' [[gene knockout]]s, loss of both copies of the gene causes severe motor impairment related to cerebellar abnormalities and lack of [[ultrasound|ultrasonic]] [[Animal communication|vocalisations]] normally elicited when pups are removed from their mothers.<ref name="Shu_2005"/> These vocalizations have important communicative roles in mother–offspring interactions. Loss of one copy was associated with impairment of ultrasonic vocalisations and a modest developmental delay. Male mice on encountering female mice produce complex ultrasonic vocalisations that have characteristics of song.<ref name="Holy_2005">{{cite journal | vauthors = Holy TE, Guo Z | title = Ultrasonic songs of male mice | journal = PLOS Biology | volume = 3 | issue = 12 | pages = e386 | date = December 2005 | pmid = 16248680 | pmc = 1275525 | doi = 10.1371/journal.pbio.0030386 | doi-access = free }}</ref> Mice that have the R552H point mutation carried by the KE family show cerebellar reduction and abnormal [[synaptic plasticity]] in striatal and [[cerebellar]] circuits.<ref name="Groszer 2008"/>

Humanized FOXP2 mice display altered [[Cortico-basal ganglia-thalamo-cortical loop|cortico-basal ganglia]] circuits. The human allele of the FOXP2 gene was transferred into the mouse embryos through [[homologous recombination]] to create humanized FOXP2 mice. The human variant of FOXP2 also had an effect on the exploratory behavior of the mice. In comparison to knockout mice with one non-functional copy of ''FOXP2'', the humanized mouse model showed opposite effects when testing its effect on the levels of dopamine, plasticity of synapses, patterns of expression in the striatum and behavior that was exploratory in nature.<ref name="Enard_2009" />

When FOXP2 expression was altered in mice, it affected many different processes including the learning motor skills and the plasticity of synapses. Additionally, FOXP2 is found more in the [[Cerebral cortex#Layer VI|sixth layer]] of the cortex than in the [[Cerebral cortex#Layer V|fifth]], and this is consistent with it having greater roles in sensory integration. FOXP2 was also found in the [[medial geniculate nucleus]] of the mouse brain, which is the processing area that auditory inputs must go through in the thalamus. It was found that its mutations play a role in delaying the development of language learning. It was also found to be highly expressed in the Purkinje cells and cerebellar nuclei of the cortico-cerebellar circuits. High FOXP2 expression has also been shown in the spiny neurons that express [[Dopamine receptor D1|type 1 dopamine receptors]] in the striatum, [[substantia nigra]], [[subthalamic nucleus]] and [[ventral tegmental area]]. The negative effects of the mutations of FOXP2 in these brain regions on motor abilities were shown in mice through tasks in lab studies. When analyzing the brain circuitry in these cases, scientists found greater levels of dopamine and decreased lengths of dendrites, which caused defects in [[long-term depression]], which is implicated in motor function learning and maintenance. Through [[EEG]] studies, it was also found that these mice had increased levels of activity in their striatum, which contributed to these results. There is further evidence for mutations of targets of the FOXP2 gene shown to have roles in [[schizophrenia]], [[epilepsy]], [[autism]], [[bipolar disorder]] and intellectual disabilities.<ref name="French_2014">{{cite journal | vauthors = French CA, Fisher SE | title = What can mice tell us about Foxp2 function? | journal = Current Opinion in Neurobiology | volume = 28 | pages = 72–9 | date = October 2014 | pmid = 25048596 | doi = 10.1016/j.conb.2014.07.003 | hdl-access = free | s2cid = 17848265 | hdl = 11858/00-001M-0000-0019-F62D-4 }}</ref>

=== Bats ===
''FOXP2'' has implications in the development of [[bat]] [[animal echolocation|echolocation]].<ref name="Preuss_2012"/><ref name="Li_2007">{{cite journal | vauthors = Li G, Wang J, Rossiter SJ, Jones G, Zhang S | title = Accelerated FoxP2 evolution in echolocating bats | journal = PLOS ONE | volume = 2 | issue = 9 | pages = e900 | date = September 2007 | pmid = 17878935 | pmc = 1976393 | doi = 10.1371/journal.pone.0000900 | veditors = Ellegren H | doi-access = free | bibcode = 2007PLoSO...2..900L }}</ref><ref name="Wilbrecht_2003">{{cite journal | vauthors = Wilbrecht L, Nottebohm F | title = Vocal learning in birds and humans | journal = Mental Retardation and Developmental Disabilities Research Reviews | volume = 9 | issue = 3 | pages = 135–48 | year = 2003 | pmid = 12953292 | doi = 10.1002/mrdd.10073 }}</ref> Contrary to apes and mice, ''FOXP2'' is extremely diverse in [[Microbat|echolocating bats]].<ref name="Li_2007" /> Twenty-two sequences of non-bat [[eutherian]] mammals revealed a total number of 20 nonsynonymous mutations in contrast to half that number of bat sequences, which showed 44 nonsynonymous mutations.<ref name="Li_2007" /> All [[cetaceans]] share three amino acid substitutions, but no differences were found between echolocating [[toothed whales]] and non-echolocating [[baleen cetaceans]].<ref name="Li_2007" /> Within bats, however, amino acid variation correlated with different echolocating types.<ref name="Li_2007" />

=== Birds ===
In [[songbird]]s, ''FOXP2'' most likely regulates genes involved in [[neuroplasticity]].<ref name="Haesler_2007">{{cite journal | vauthors = Haesler S, Rochefort C, Georgi B, Licznerski P, Osten P, Scharff C | title = Incomplete and inaccurate vocal imitation after knockdown of FoxP2 in songbird basal ganglia nucleus Area X | journal = PLOS Biology | volume = 5 | issue = 12 | pages = e321 | date = December 2007 | pmid = 18052609 | pmc = 2100148 | doi = 10.1371/journal.pbio.0050321 | doi-access = free }}</ref><ref name="Teramitsu_2006">{{cite journal | vauthors = Teramitsu I, White SA | author-link2 = Stephanie A. White | title = FoxP2 regulation during undirected singing in adult songbirds | journal = The Journal of Neuroscience | volume = 26 | issue = 28 | pages = 7390–4 | date = July 2006 | pmid = 16837586 | doi = 10.1523/JNEUROSCI.1662-06.2006 | url = https://doi.org/10.1523/JNEUROSCI.1662-06.2006 | pmc = 2683919 }}</ref> [[Gene knockdown]] of ''FOXP2'' in area X of the [[basal ganglia]] in songbirds results in incomplete and inaccurate song imitation.<ref name="Haesler_2007" /> Overexpression of ''FOXP2'' was accomplished through injection of [[adeno-associated virus]] serotype 1 (AAV1) into area X of the brain. This overexpression produced similar effects to that of knockdown; juvenile zebra finch birds were unable to accurately imitate their tutors.<ref>{{cite journal | vauthors = Heston JB, White SA | author-link2 = Stephanie A. White | title = Behavior-linked FoxP2 regulation enables zebra finch vocal learning | journal = The Journal of Neuroscience | volume = 35 | issue = 7 | pages = 2885–94 | date = February 2015 | pmid = 25698728 | doi = 10.1523/JNEUROSCI.3715-14.2015 | url = https://doi.org/10.1523/JNEUROSCI.3715-14.2015 | pmc = 4331621 }}</ref> Similarly, in adult canaries, higher ''FOXP2'' levels also correlate with song changes.<ref name="Haesler_2004"/>

Levels of ''FOXP2'' in adult zebra finches are significantly higher when males direct their song to females than when they sing song in other contexts.<ref name="Teramitsu_2006"/> "Directed" singing refers to when a male is singing to a female usually for a courtship display. "Undirected" singing occurs when for example, a male sings when other males are present or is alone.<ref>{{cite journal | vauthors = Jarvis ED, Scharff C, Grossman MR, Ramos JA, Nottebohm F | title = For whom the bird sings: context-dependent gene expression | journal = Neuron | volume = 21 | issue = 4 | pages = 775–88 | date = October 1998 | pmid = 9808464 | doi = 10.1016/s0896-6273(00)80594-2 | s2cid = 13893471 | doi-access = free }}</ref> Studies have found that FoxP2 levels vary depending on the social context. When the birds were singing undirected song, there was a decrease of FoxP2 expression in Area X. This downregulation was not observed and FoxP2 levels remained stable in birds singing directed song.<ref name="Teramitsu_2006"/>

Differences between song-learning and non-song-learning birds have been shown to be caused by differences in ''FOXP2'' [[gene expression]], rather than differences in the amino acid sequence of the ''FOXP2'' protein.

=== Zebrafish ===
In [[zebrafish]], FOXP2 is expressed in the ventral and [[dorsal thalamus]], [[telencephalon]], [[diencephalon]] where it likely plays a role in nervous system development. The zebrafish FOXP2 gene has an 85% similarity to the human FOX2P ortholog.<ref name="Bonkowsky_2005">{{cite journal | vauthors = Bonkowsky JL, Chien CB | title = Molecular cloning and developmental expression of foxP2 in zebrafish | journal = Developmental Dynamics | volume = 234 | issue = 3 | pages = 740–6 | date = November 2005 | pmid = 16028276 | doi = 10.1002/dvdy.20504 | s2cid = 24771138 | doi-access = free }}</ref>