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Related Experiment Videos

Hsp90 selectively modulates phenotype in vertebrate development.

Patricia L Yeyati1, Ruth M Bancewicz, John Maule

  • 1Medical Research Council Human Genetics Unit, Western General Hospital, Edinburgh, United Kingdom. patricia.yeyati@hgu.mrc.ac.uk

Plos Genetics
|April 3, 2007
PubMed
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Heat shock protein 90 (Hsp90) inhibition in zebrafish reveals cryptic genetic variation, impacting developmental anomalies. Mild Hsp90 perturbation influences the severity and penetrance of heritable eye malformations, highlighting genotype-environment interactions.

Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Chaperones

Background:

  • Heat shock protein 90 (Hsp90) is a molecular chaperone known to buffer genetic variation in model organisms.
  • Its role in vertebrate developmental malformations and variable expressivity is less understood.
  • Previous studies in flies and plants suggested Hsp90 masks underlying genetic diversity.

Purpose of the Study:

  • To investigate the role of Hsp90 in buffering genetic variation in zebrafish.
  • To determine if Hsp90 inhibition affects the penetrance and expressivity of developmental eye malformations.
  • To explore the molecular mechanisms underlying Hsp90's influence on development.

Main Methods:

  • Zebrafish were treated with Hsp90 inhibitors at sub-threshold levels, avoiding heat shock response.

Related Experiment Videos

  • Analysis of established mutant strains (sunrise, dreumes) and a novel strain exhibiting eye malformations.
  • Inbreeding of carrier parents to assess oligogenic inheritance and developmental stability.

    • Main Results:

    • Hsp90 inhibition exacerbated the 'sunrise' pax6b mutation phenotype and ameliorated the 'dreumes' sufu mutation phenotype.
    • A novel spectrum of anophthalmia, microphthalmia, and nanophthalmia complex malformations was uncovered.
    • Developmental stability decreased, evidenced by increased asymmetry in affected phenotypes.
    • Oligogenic inheritance was suggested for the novel malformation complex.

    Conclusions:

    • Hsp90 inhibition in zebrafish can decrease developmental stability, unlike in Drosophila.
    • Mild Hsp90 perturbation influences the variable expressivity and penetrance of developmental anomalies.
    • This suggests Hsp90 plays a critical role in modulating genotype-environment interactions during development.