Distinct regulatory mechanisms act to establish and maintain pax3 expression in the developing neural tube

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• dc.contributor.author Moore, Steven
• dc.contributor.author Ribes, Vanessa
• dc.contributor.author Terriente, Javier
• dc.contributor.author Wilkinson, David
• dc.contributor.author Relaix, Frederic
• dc.contributor.author Briscoe, James
• dc.date.accessioned 2024-03-26T07:09:44Z
• dc.date.available 2024-03-26T07:09:44Z
• dc.date.issued 2013
• dc.description.abstract Pattern formation in developing tissues is driven by the interaction of extrinsic signals with intrinsic transcriptional networks that together establish spatially and temporally restricted profiles of gene expression. How this process is orchestrated at the molecular level by genomic cis-regulatory modules is one of the central questions in developmental biology. Here we have addressed this by analysing the regulation of Pax3 expression in the context of the developing spinal cord. Pax3 is induced early during neural development in progenitors of the dorsal spinal cord and is maintained as pattern is subsequently elaborated, resulting in the segregation of the tissue into dorsal and ventral subdivisions. We used a combination of comparative genomics and transgenic assays to define and dissect several functional cis-regulatory modules associated with the Pax3 locus. We provide evidence that the coordinated activity of two modules establishes and refines Pax3 expression during neural tube development. Mutational analyses of the initiating element revealed that in addition to Wnt signaling, Nkx family homeodomain repressors restrict Pax3 transcription to the presumptive dorsal neural tube. Subsequently, a second module mediates direct positive autoregulation and feedback to maintain Pax3 expression. Together, these data indicate a mechanism by which transient external signals are converted into a sustained expression domain by the activities of distinct regulatory elements. This transcriptional logic differs from the cross-repression that is responsible for the spatiotemporal patterns of gene expression in the ventral neural tube, suggesting that a variety of circuits are deployed within the neural tube regulatory network to establish and elaborate pattern formation.
• dc.format.mimetype application/pdf
• dc.identifier.citation Moore S, Ribes V, Terriente J, Wilkinson D, Relaix F, Briscoe J. Distinct regulatory mechanisms act to establish and maintain pax3 expression in the developing neural tube. PLoS Genet. 2013 Oct 3;9(10):e1003811. DOI: 10.1371/journal.pgen.1003811
• dc.identifier.doi http://dx.doi.org/10.1371/journal.pgen.1003811
• dc.identifier.issn 1553-7390
• dc.identifier.uri http://hdl.handle.net/10230/59561
• dc.language.iso eng
• dc.publisher Public Library of Science (PLoS)
• dc.relation.ispartof PLoS Genetics. 2013 Oct 3;9(10):e1003811
• dc.rights © 2013 Moore et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/deed.en
• dc.subject.other Sistema nerviós central
• dc.subject.other Mamífers -- Genètica
• dc.subject.other ADN
• dc.title Distinct regulatory mechanisms act to establish and maintain pax3 expression in the developing neural tube
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion