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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): e1002145. doi:10.1371/journal.pgen.1002145.

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Datensatz-Permalink: http://hdl.handle.net/11858/00-001M-0000-0011-588C-7 Versions-Permalink: http://hdl.handle.net/11858/00-001M-0000-0011-589B-5
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Vernes_etal_journal.pgen.1002145.pdf (Verlagsversion), 2MB
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Vernes, Sonja C.1, Autor              
Oliver, P. L. , Autor
Spiteri, E., Autor
Lockstone, H. E., Autor
Puliyadi, R., Autor
Taylor, J. M. , Autor
Ho, J., Autor
Mombereau, C., Autor
Brewer, A., Autor
Lowy, E., Autor
Nicod, J., Autor
Groszer, M., Autor
Baban, D., Autor
Sahgal, N., Autor
Cazier, J-B, Autor
Ragoussis, J., Autor
Davies, K. E., Autor
Geschwind, D. H., Autor
Fisher, Simon E.2, Autor              
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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 Zusammenfassung: 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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Sprache(n): eng - Englisch
 Datum: 2011-05-072011-07-07
 Publikationsstatus: Online publiziert
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 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1371/journal.pgen.1002145
 Art des Abschluß: -

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Titel: PLoS Genetics
  Andere : PLoS Genet.
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: San Francisco, CA : Public Library of Science
Seiten: - Band / Heft: 7 (7) Artikelnummer: e1002145 Start- / Endseite: - Identifikator: ISSN: 1553-7390
CoNE: http://pubman.mpdl.mpg.de/cone/journals/resource/1000000000017180