Molecular changes associated with teratogen-induced cyclopia

Authors

  • Evyn J. Loucks,

    1. Children's Memorial Research Center Program in Developmental Biology, Chicago, Illinois
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  • Tyler Schwend,

    1. Children's Memorial Research Center Program in Developmental Biology, Chicago, Illinois
    2. Northwestern University Feinberg School of Medicine Integrated Graduate Program, Chicago, Illinois
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  • Sara C. Ahlgren

    Corresponding author
    1. Children's Memorial Research Center Program in Developmental Biology, Chicago, Illinois
    2. Northwestern University Feinberg School of Medicine Integrated Graduate Program, Chicago, Illinois
    3. Northwestern University Feinberg School of Medicine, Department of Pediatrics, Chicago, Illinois
    • Program in Developmental Biology, Children's Memorial Research Center, 2300 Children's Plaza, Box 204, Chicago, IL 60640
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  • This article is a US Government work and, as such, is in the public domain in the United States of America.

Abstract

BACKGROUND: Exposure of zebrafish embryos to a number of teratogens results in cyclopia, but little is known about the underlying molecular changes. METHODS: Using zebrafish embryos, we compare the effects cyclopamine, forskolin, and ethanol delivered starting just before gastrulation, on gene expression in early axial tissues and forebrain development. RESULTS: Although all three teratogens suppress gli1 expression, they do so with variable kinetics, suggesting that while suppression of Shh signaling is a common outcome of these three teratogens, it is not a common cause of the cyclopia. Instead, all teratogens studied produce a series of changes in the expression of gsc and six3b present in early axial development, as well as a later suppression of neural crest cell marker dlx3b. Ethanol and forskolin, but not cyclopamine, exposure reduced anterior markers, which most likely contributes to the cyclopic phenotype. CONCLUSIONS: These data suggest that each teratogen exposure leads to a unique set of molecular changes that underlie the single phenotype of cyclopia. Birth Defects Research (Part A), 2007. © 2007 Wiley-Liss, Inc.

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