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Zic transcription factors regulate retinoic acid metabolism during zebrafish neural development Open Access


Other title
retinoic acid
neural tube
Type of item
Degree grantor
University of Alberta
Author or creator
Drummond, Danna L
Supervisor and department
Waskiewicz, Andrew (Biological Sciences)
Examining committee member and department
Godbout, Roseline (Medical Oncology)
Allison, William (Biological Sciences)
Department of Biological Sciences
Molecular Biology and Genetics
Date accepted
Graduation date
Master of Science
Degree level
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.
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