Zic transcription factors regulate retinoic acid metabolism during zebrafish neural development

  • Author / Creator
    Drummond, Danna L
  • 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.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Department of Biological Sciences
  • Specialization
    • Molecular Biology and Genetics
  • Supervisor / co-supervisor and their department(s)
    • Waskiewicz, Andrew (Biological Sciences)
  • Examining committee members and their departments
    • Allison, William (Biological Sciences)
    • Godbout, Roseline (Medical Oncology)