A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice.
It has been proposed that two amino acid substitutions in the transcription factor FOXP2 have been positively selected during human evolution due to effects on aspects of speech and language. Here, we introduce these substitutions into the endogenous Foxp2 gene of mice. Although these mice are generally healthy, they have qualitatively different ultrasonic vocalizations, decreased exploratory behavior and decreased dopamine concentrations in the brain suggesting that the humanized Foxp2 allele affects basal ganglia. In the striatum, a part of the basal ganglia affected in humans with a speech deficit due to a nonfunctional FOXP2 allele, we find that medium spiny neurons have increased dendrite lengths and increased synaptic plasticity. Since mice carrying one nonfunctional Foxp2 allele show opposite effects, this suggests that alterations in cortico-basal ganglia circuits might have been important for the evolution of speech and language in humans.
Enard
Wolfgang
W
Max-Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103 Leipzig, Germany. enard@eva.mpg.de
Gehre
Sabine
S
Hammerschmidt
Kurt
K
Hölter
Sabine M
SM
Blass
Torsten
T
Somel
Mehmet
M
Brückner
Martina K
MK
Schreiweis
Christiane
C
Winter
Christine
C
Sohr
Reinhard
R
Becker
Lore
L
Wiebe
Victor
V
Nickel
Birgit
B
Giger
Thomas
T
Müller
Uwe
U
Groszer
Matthias
M
Adler
Thure
T
Aguilar
Antonio
A
Bolle
Ines
I
Calzada-Wack
Julia
J
Dalke
Claudia
C
Ehrhardt
Nicole
N
Favor
Jack
J
Fuchs
Helmut
H
Gailus-Durner
Valérie
V
Hans
Wolfgang
W
Hölzlwimmer
Gabriele
G
Javaheri
Anahita
A
Kalaydjiev
Svetoslav
S
Kallnik
Magdalena
M
Kling
Eva
E
Kunder
Sandra
S
Mossbrugger
Ilona
I
Naton
Beatrix
B
Racz
Ildikó
I
Rathkolb
Birgit
B
Rozman
Jan
J
Schrewe
Anja
A
Busch
Dirk H
DH
Graw
Jochen
J
Ivandic
Boris
B
Klingenspor
Martin
M
Klopstock
Thomas
T
Ollert
Markus
M
Quintanilla-Martinez
Leticia
L
Schulz
Holger
H
Wolf
Eckhard
E
Wurst
Wolfgang
W
Zimmer
Andreas
A
Fisher
Simon E
SE
Morgenstern
Rudolf
R
Arendt
Thomas
T
de Angelis
Martin Hrabé
MH
Fischer
Julia
J
Schwarz
Johannes
J
Pääbo
Svante
S
D019943:Amino Acid Substitution; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism*; D005075:Biological Evolution; D003712:Dendrites / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D015870:Gene Expression; D006579:Heterozygote; D006801:Humans; D007802:Language; D036881:Long-Term Synaptic Depression; D051379:Mice; D009434:Neural Pathways; D009473:Neuronal Plasticity; D013060:Speech; D014828:Vocalization, Animal
C465448:FOXP2 protein, human; D051858:Forkhead Transcription Factors; D004298:Dopamine