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Humanized Foxp2 Accelerates Making Transitions From Declarative to Procedural Learning


ABSTRACT: Purpose: Foxp2 is the first and for now the only gene connected to speech and language in humans. Two aminoacid substitutions took place in this protein during recent human evolution, after our split from the last common ancestor with chimpanzees, and are most likely to have undergone positive selection in human lineage (Enard et al., 2002). Methods: Transgenic mice in which the wild-type (murine) version of Foxp2 was replaced with the one bearing two human-specific amino acid substitutions (i.e. "humanized" Foxp2) - Foxp2hum/hum, have been compared to their wild-type (WT) counterparts in terms of behavior, electrophysiology and striatal gene expression. The latter was analyzed through RNA-sequencing performed on pooled indexed libraries on three flow cells on Illumina GAIIx. The reads were mapped to mouse genome (mm9) by TopHat 1.4.1 and were counted using Bedtools. mRNA profiles were obtained with more than 20 million reads for every sample. Differential gene expression was analyzed with DESeq using multifactor model (Anders and Huber, 2010). Results: Wild-type and Foxp2hum/hum mice did not show any significant differences in expression at individual gene level, neither in dorsomedial nor in dorsolateral striatum. However, when genes were grouped into functional categories and analyzed accordingly, this revealed a significant downregulation of functional categories related to synaptic signalling and plasticity in dorsomedial striatum of Foxp2hum/hum mice. RNA-sequencing was performed on dorsomedial and dorsolateral striatum of wild-type and Foxp2hum/hum mice, on three flow cells Illumina GAIIx. The libraries from each sample were indexed and pooled together.

ORGANISM(S): Mus musculus

SUBMITTER: Cemil Kerimoglu 

PROVIDER: E-GEOD-60659 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance.

Schreiweis Christiane C   Bornschein Ulrich U   Burguière Eric E   Kerimoglu Cemil C   Schreiter Sven S   Dannemann Michael M   Goyal Shubhi S   Rea Ellis E   French Catherine A CA   Puliyadi Rathi R   Groszer Matthias M   Fisher Simon E SE   Mundry Roger R   Winter Christine C   Hevers Wulf W   Pääbo Svante S   Enard Wolfgang W   Graybiel Ann M AM  

Proceedings of the National Academy of Sciences of the United States of America 20140915 39


The acquisition of language and speech is uniquely human, but how genetic changes might have adapted the nervous system to this capacity is not well understood. Two human-specific amino acid substitutions in the transcription factor forkhead box P2 (FOXP2) are outstanding mechanistic candidates, as they could have been positively selected during human evolution and as FOXP2 is the sole gene to date firmly linked to speech and language development. When these two substitutions are introduced into  ...[more]

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