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Related Experiment Videos

Cis-acting regulatory sequences governing Wnt-1 expression in the developing mouse CNS

Y Echelard1, G Vassileva, A P McMahon

  • 1Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110.

Development (Cambridge, England)
|August 1, 1994
PubMed
Summary

The Wnt-1 gene is crucial for midbrain development in mice. Researchers identified a regulatory element controlling Wnt-1 expression, offering insights into neural development and neural crest cell analysis.

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Area of Science:

  • Developmental Biology
  • Neuroscience
  • Genetics

Background:

  • The protooncogene Wnt-1 encodes a signaling molecule essential for early brain development, particularly the midbrain.
  • Wnt-1 expression defines the presumptive midbrain region, and its absence results in the loss of this brain area.
  • Wnt-1 expression is restricted to the central nervous system (CNS) during later stages of neural tube closure.

Purpose of the Study:

  • To investigate the regulatory mechanisms governing Wnt-1 gene expression during mouse embryonic development.
  • To identify cis-acting elements responsible for controlling the spatial and temporal expression of Wnt-1.
  • To explore the potential of Wnt-1 regulatory elements for analyzing neural crest cell development.

Main Methods:

  • Analysis of Wnt-1-lacZ reporter constructs spanning approximately 30 kb of the Wnt-1 locus.

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  • Characterization of a 5.5 kb cis-acting enhancer element located 3' to the Wnt-1 gene.
  • Examination of transgene expression patterns in developing mouse embryos, including migrating neural crest cells.

    • Main Results:

    • A 5.5 kb enhancer element located 3' to the Wnt-1 locus was identified, which directs correct temporal and spatial expression of a lacZ reporter gene.
    • Wnt-1-lacZ transgenes were ectopically expressed in migrating neural crest cells derived from the dorsal CNS.
    • Ectopic expression in neural crest cells may be due to beta-galactosidase activity perdurance or transient de novo transgene activation.

    Conclusions:

    • The identified 3' enhancer is a key regulatory element controlling Wnt-1 expression in the developing CNS.
    • Wnt-1 regulation is complex and involves elements that can influence expression in neural crest cells.
    • Wnt-1 transgene expression provides a valuable tool for studying neural crest development and cell signaling in the mammalian CNS.