PUBLICATION

Distinct regulatory mechanisms act to establish and maintain Pax3 expression in the developing neural tube

Authors
Moore, S., Ribes, V., Terriente, J., Wilkinson, D., Relaix, F., Briscoe, J.
ID
ZDB-PUB-181001-3
Date
2013
Source
PLoS Genetics   9: e1003811 (Journal)
Registered Authors
Wilkinson, David
Keywords
none
MeSH Terms
  • Body Patterning/genetics
  • DNA-Binding Proteins/genetics
  • Mice/genetics*
  • Mice/metabolism
  • Animals, Genetically Modified
  • Embryonic Development/genetics*
  • Gene Expression Regulation, Developmental
  • Paired Box Transcription Factors/genetics*
  • Paired Box Transcription Factors/metabolism
  • Zebrafish/growth & development
  • Spinal Cord/growth & development
  • Chick Embryo
  • DNA Mutational Analysis
  • Animals
  • PAX3 Transcription Factor
  • Gene Regulatory Networks/genetics*
  • Neural Tube/growth & development*
  • Wnt Signaling Pathway
(all 18)
PubMed
24098141 Full text @ PLoS Genet.
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.
Genes / Markers
Figures
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Expression
Phenotype
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
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    Fish
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    Antibodies
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    Engineered Foreign Genes
    Marker Marker Type Name
    GFPEFGGFP
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    Mapping
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    Citation
    Moore, S., Ribes, V., Terriente, J., Wilkinson, D., Relaix, F., Briscoe, J. (2013) Distinct regulatory mechanisms act to establish and maintain Pax3 expression in the developing neural tube. PLoS Genetics. 9:e1003811.