A Humanized Version of Foxp2 Affects Cortico-Basal Ganglia Circuits in Mice

Wolfgang Enard; Sabine Gehre; Kurt Hammerschmidt; Sabine M. Hölter; Torsten Blass; Mehmet Somel; Martina K. Brückner; Christiane Schreiweis; Christine Winter; Reinhard Sohr; Lore Becker; Victor Wiebe; Birgit Nickel; Thomas Giger; Uwe Müller; Matthias Groszer; Thure Adler; Antonio Aguilar; Ines Bolle; Julia Calzada-Wack; Claudia Dalke; Nicole Ehrhardt; Jack Favor; Helmut Fuchs; Valérie Gailus-Durner; Wolfgang Hans; Gabriele Hölzlwimmer; Anahita Javaheri; Svetoslav Kalaydjiev; Magdalena Kallnik; Eva Kling; Sandra Kunder; Ilona Moßbrugger; Beatrix Naton; Ildikó Racz; Birgit Rathkolb; Jan Rozman; Anja Schrewe; Dirk H. Busch; Jochen Graw; Boris Ivandic; Martin Klingenspor; Thomas Klopstock; Markus Ollert; Leticia Quintanilla-Martinez; Holger Schulz; Eckhard Wolf; Wolfgang Wurst; Andreas Zimmer; Simon E. Fisher; Rudolf Morgenstern; Thomas Arendt; Martin Hrabé de Angelis; Julia Fischer; Johannes Schwarz; Svante Pääbo

doi:10.1016/j.cell.2009.03.041

A Humanized Version of Foxp2 Affects Cortico-Basal Ganglia Circuits in Mice

Wolfgang Enard, Sabine Gehre, Kurt Hammerschmidt, Sabine M. Hölter, Torsten Blass, Mehmet Somel, Martina K. Brückner, Christiane Schreiweis, Christine Winter, Reinhard Sohr, Lore Becker, Victor Wiebe, Birgit Nickel, Thomas Giger, Uwe Müller, Matthias Groszer, Thure Adler, Antonio Aguilar, Ines Bolle, Julia Calzada-WackClaudia Dalke, Nicole Ehrhardt, Jack Favor, Helmut Fuchs, Valérie Gailus-Durner, Wolfgang Hans, Gabriele Hölzlwimmer, Anahita Javaheri, Svetoslav Kalaydjiev, Magdalena Kallnik, Eva Kling, Sandra Kunder, Ilona Moßbrugger, Beatrix Naton, Ildikó Racz, Birgit Rathkolb, Jan Rozman, Anja Schrewe, Dirk H. Busch, Jochen Graw, Boris Ivandic, Martin Klingenspor, Thomas Klopstock, Markus Ollert, Leticia Quintanilla-Martinez, Holger Schulz, Eckhard Wolf, Wolfgang Wurst, Andreas Zimmer, Simon E. Fisher, Rudolf Morgenstern, Thomas Arendt, Martin Hrabé de Angelis, Julia Fischer, Johannes Schwarz, Svante Pääbo

Research output: Contribution to journal › Article › peer-review

Abstract

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. For a video summary of this article, see the PaperFlick file available with the online Supplemental Data. © 2009 Elsevier Inc. All rights reserved.

Original language	English
Pages (from-to)	961-971
Number of pages	10
Journal	Cell
Volume	137
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2009.03.041
Publication status	Published - 29 May 2009

Keywords

EVO_ECOL
HUMDISEASE
SYSNEURO

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10.1016/j.cell.2009.03.041

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Enard, W., Gehre, S., Hammerschmidt, K., Hölter, S. M., Blass, T., Somel, M., Brückner, M. K., Schreiweis, C., Winter, C., Sohr, R., Becker, L., Wiebe, V., Nickel, B., Giger, T., Müller, U., Groszer, M., Adler, T., Aguilar, A., Bolle, I., ... Pääbo, S. (2009). A Humanized Version of Foxp2 Affects Cortico-Basal Ganglia Circuits in Mice. Cell, 137(5), 961-971. https://doi.org/10.1016/j.cell.2009.03.041

@article{01eb3860e8f14664a91c2109e10b7887,

title = "A Humanized Version of Foxp2 Affects Cortico-Basal Ganglia Circuits in Mice",

abstract = "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. For a video summary of this article, see the PaperFlick file available with the online Supplemental Data. {\textcopyright} 2009 Elsevier Inc. All rights reserved.",

keywords = "EVO_ECOL, HUMDISEASE, SYSNEURO",

author = "Wolfgang Enard and Sabine Gehre and Kurt Hammerschmidt and H{\"o}lter, {Sabine M.} and Torsten Blass and Mehmet Somel and Br{\"u}ckner, {Martina K.} and Christiane Schreiweis and Christine Winter and Reinhard Sohr and Lore Becker and Victor Wiebe and Birgit Nickel and Thomas Giger and Uwe M{\"u}ller and Matthias Groszer and Thure Adler and Antonio Aguilar and Ines Bolle and Julia Calzada-Wack and Claudia Dalke and Nicole Ehrhardt and Jack Favor and Helmut Fuchs and Val{\'e}rie Gailus-Durner and Wolfgang Hans and Gabriele H{\"o}lzlwimmer and Anahita Javaheri and Svetoslav Kalaydjiev and Magdalena Kallnik and Eva Kling and Sandra Kunder and Ilona Mo{\ss}brugger and Beatrix Naton and Ildik{\'o} Racz and Birgit Rathkolb and Jan Rozman and Anja Schrewe and Busch, {Dirk H.} and Jochen Graw and Boris Ivandic and Martin Klingenspor and Thomas Klopstock and Markus Ollert and Leticia Quintanilla-Martinez and Holger Schulz and Eckhard Wolf and Wolfgang Wurst and Andreas Zimmer and Fisher, {Simon E.} and Rudolf Morgenstern and Thomas Arendt and {Hrab{\'e} de Angelis}, Martin and Julia Fischer and Johannes Schwarz and Svante P{\"a}{\"a}bo",

year = "2009",

month = may,

day = "29",

doi = "10.1016/j.cell.2009.03.041",

language = "English",

volume = "137",

pages = "961--971",

journal = "Cell",

issn = "1097-4172",

publisher = "Cell Press",

number = "5",

}

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, Hrabé de Angelis, M, Fischer, J, Schwarz, J & Pääbo, S 2009, 'A Humanized Version of Foxp2 Affects Cortico-Basal Ganglia Circuits in Mice', Cell, vol. 137, no. 5, pp. 961-971. https://doi.org/10.1016/j.cell.2009.03.041

TY - JOUR

T1 - A Humanized Version of Foxp2 Affects Cortico-Basal Ganglia Circuits in Mice

AU - Enard, Wolfgang

AU - Gehre, Sabine

AU - Hammerschmidt, Kurt

AU - Hölter, Sabine M.

AU - Blass, Torsten

AU - Somel, Mehmet

AU - Brückner, Martina K.

AU - Schreiweis, Christiane

AU - Winter, Christine

AU - Sohr, Reinhard

AU - Becker, Lore

AU - Wiebe, Victor

AU - Nickel, Birgit

AU - Giger, Thomas

AU - Müller, Uwe

AU - Groszer, Matthias

AU - Adler, Thure

AU - Aguilar, Antonio

AU - Bolle, Ines

AU - Calzada-Wack, Julia

AU - Dalke, Claudia

AU - Ehrhardt, Nicole

AU - Favor, Jack

AU - Fuchs, Helmut

AU - Gailus-Durner, Valérie

AU - Hans, Wolfgang

AU - Hölzlwimmer, Gabriele

AU - Javaheri, Anahita

AU - Kalaydjiev, Svetoslav

AU - Kallnik, Magdalena

AU - Kling, Eva

AU - Kunder, Sandra

AU - Moßbrugger, Ilona

AU - Naton, Beatrix

AU - Racz, Ildikó

AU - Rathkolb, Birgit

AU - Rozman, Jan

AU - Schrewe, Anja

AU - Busch, Dirk H.

AU - Graw, Jochen

AU - Ivandic, Boris

AU - Klingenspor, Martin

AU - Klopstock, Thomas

AU - Ollert, Markus

AU - Quintanilla-Martinez, Leticia

AU - Schulz, Holger

AU - Wolf, Eckhard

AU - Wurst, Wolfgang

AU - Zimmer, Andreas

AU - Fisher, Simon E.

AU - Morgenstern, Rudolf

AU - Arendt, Thomas

AU - Hrabé de Angelis, Martin

AU - Fischer, Julia

AU - Schwarz, Johannes

AU - Pääbo, Svante

PY - 2009/5/29

Y1 - 2009/5/29

N2 - 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. For a video summary of this article, see the PaperFlick file available with the online Supplemental Data. © 2009 Elsevier Inc. All rights reserved.

AB - 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. For a video summary of this article, see the PaperFlick file available with the online Supplemental Data. © 2009 Elsevier Inc. All rights reserved.

KW - EVO_ECOL

KW - HUMDISEASE

KW - SYSNEURO

U2 - 10.1016/j.cell.2009.03.041

DO - 10.1016/j.cell.2009.03.041

M3 - Article

C2 - 19490899

SN - 1097-4172

VL - 137

SP - 961

EP - 971

JO - Cell

JF - Cell

IS - 5

ER -

A Humanized Version of Foxp2 Affects Cortico-Basal Ganglia Circuits in Mice

Abstract

Keywords

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