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  • http://hdl.handle.net/10402/era.24879
  • Zic transcription factors regulate retinoic acid metabolism during zebrafish neural development
  • Drummond, Danna L
  • English
  • neural tube
    hindbrain
    retinoic acid
    zebrafish
  • Dec 21, 2011 11:13 AM
  • Thesis
  • English
  • Adobe PDF
  • 212065897 bytes
  • Retinoic acid (RA) has a crucial role in embryonic nervous system development - controlling anterior-posterior patterning, neural differentiation, and cell proliferation. During zebrafish embryogenesis, levels of RA are tightly regulated by the combinatorial action of synthesis and degradation enzymes, such as aldh1a2 and cyp26a1. We have identified a novel regulatory interaction between Zinc finger of the cerebellum 2a/2b, Zic2a2b, transcription factors and RA metabolism genes. Using morpholino-mediated knockdown in conjunction with exogenous alterations to RA levels, we found that Zic2a2b regulates both cyp26a1 and aldh1a2 gene expression. Phenotypes resulting from Zic2a2b-depletion are reminiscent of reduced embryonic RA levels – reduction in size of posterior rhombomeres and the spinal cord. Additionally, defects in the posterior-most class of branchiomotor neurons, the vagal neurons, are visible - a defect that is completely rescued with exogenous RA supplementation. We suggest a model whereby Zic2a2b acts upstream of aldh1a2 in modulating RA levels during embryogenesis.
  • Master's
  • Master of Science
  • Department of Biological Sciences
  • Molecular Biology and Genetics
  • Spring 2012
  • Waskiewicz, Andrew (Biological Sciences)
  • Allison, William (Biological Sciences)
    Godbout, Roseline (Medical Oncology)