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  Foxp2 regulates gene networks implicated in neurite outgrowth in the developing brain

Vernes, S. C., Oliver, P. L., Spiteri, E., Lockstone, H. E., Puliyadi, R., Taylor, J. M., et al. (2011). Foxp2 regulates gene networks implicated in neurite outgrowth in the developing brain. PLoS Genetics, 7(7):. doi:10.1371/journal.pgen.1002145.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0011-588C-7 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0011-589B-5
Genre: Journal Article

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Vernes, Sonja C.1, Author              
Oliver, P. L. , Author
Spiteri, E., Author
Lockstone, H. E., Author
Puliyadi, R., Author
Taylor, J. M. , Author
Ho, J., Author
Mombereau, C., Author
Brewer, A., Author
Lowy, E., Author
Nicod, J., Author
Groszer, M., Author
Baban, D., Author
Sahgal, N., Author
Cazier, J-B, Author
Ragoussis, J., Author
Davies, K. E., Author
Geschwind, D. H., Author
Fisher, Simon E.2, Author              
Affiliations:
1Wellcome Trust Centre for Human Genetics, University of Oxford, escidoc:persistent22              
2Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society, escidoc:792549              

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 Abstract: Forkhead-box protein P2 is a transcription factor that has been associated with intriguing aspects of cognitive function in humans, non-human mammals, and song-learning birds. Heterozygous mutations of the human FOXP2 gene cause a monogenic speech and language disorder. Reduced functional dosage of the mouse version (Foxp2) causes deficient cortico-striatal synaptic plasticity and impairs motor-skill learning. Moreover, the songbird orthologue appears critically important for vocal learning. Across diverse vertebrate species, this well-conserved transcription factor is highly expressed in the developing and adult central nervous system. Very little is known about the mechanisms regulated by Foxp2 during brain development. We used an integrated functional genomics strategy to robustly define Foxp2-dependent pathways, both direct and indirect targets, in the embryonic brain. Specifically, we performed genome-wide in vivo ChIP–chip screens for Foxp2-binding and thereby identified a set of 264 high-confidence neural targets under strict, empirically derived significance thresholds. The findings, coupled to expression profiling and in situ hybridization of brain tissue from wild-type and mutant mouse embryos, strongly highlighted gene networks linked to neurite development. We followed up our genomics data with functional experiments, showing that Foxp2 impacts on neurite outgrowth in primary neurons and in neuronal cell models. Our data indicate that Foxp2 modulates neuronal network formation, by directly and indirectly regulating mRNAs involved in the development and plasticity of neuronal connections

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Language(s): eng - English
 Dates: 2011-05-072011-07-07
 Publication Status: Published online
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 Rev. Method: Peer
 Identifiers: DOI: 10.1371/journal.pgen.1002145
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Title: PLoS Genetics
  Other : PLoS Genet.
Source Genre: Journal
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Publ. Info: San Francisco, CA : Public Library of Science
Pages: - Volume / Issue: 7 (7) Sequence Number: e1002145 Start / End Page: - Identifier: ISSN: 1553-7390
CoNE: http://pubman.mpdl.mpg.de/cone/journals/resource/1000000000017180