Aristaless Related Homeobox

Mutations in the Aristaless Related Homeobox (ARX) gene are associated with a spectrum of structural (lissencephaly) and functional (epilepsy and intellectual disabilities) neurodevelopmental disorders. How mutations in this single transcription factor can result in such a broad range of phenotypes...

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Veröffentlicht in:PloS one 2017-01, Vol.12 (1), p.e0170282
Hauptverfasser: Cho, Il-Taeg, Lim, Youngshin, Golden, Jeffrey A, Cho, Ginam
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Sprache:eng
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Zusammenfassung:Mutations in the Aristaless Related Homeobox (ARX) gene are associated with a spectrum of structural (lissencephaly) and functional (epilepsy and intellectual disabilities) neurodevelopmental disorders. How mutations in this single transcription factor can result in such a broad range of phenotypes remains poorly understood. We hypothesized that ARX functions through distinct interactions with specific transcription factors/cofactors to regulate unique target genes in different cell types. To identify ARX interacting proteins, we performed an unbiased proteomics screen and identified several components of the Wnt/[beta]-catenin signaling pathway, including [beta]-catenin (CTNNB1), B-cell CLL/lymphoma 9 (BCL9) and leucine rich repeat flightless interacting protein 2 (LRRFIP2), in cortical progenitor cells. Our data show that ARX positively regulates Wnt/ [beta]-catenin signaling and that the C-terminal domain of ARX interacts with the armadillo repeats in [beta]-catenin to promote Wnt/[beta]-catenin signaling. In addition, we found BCL9 and P300 also interact with ARX to modulate Wnt/[beta]-catenin signaling. These data provide new insights into how ARX can uniquely regulate cortical neurogenesis, and connect the function of ARX with Wnt/[beta]-catenin signaling.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0170282