Molecular changes associated with teratogen-induced cyclopia.
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.
Loucks
Evyn J
EJ
Children's Memorial Research Center Program in Developmental Biology, Chicago, Illinois, USA.
Schwend
Tyler
T
Ahlgren
Sara C
SC
D000818:Animals; D001483:Base Sequence; D005576:Colforsin / Q000633:toxicity; D017931:DNA Primers / Q000235:genetics; D000431:Ethanol / Q000633:toxicity; D005124:Eye Abnormalities / Q000139:chemically induced* / Q000196:embryology / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005801:Genes, Homeobox / Q000187:drug effects; D051956:Goosecoid Protein / Q000235:genetics; D053823:Hedgehog Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D013723:Teratogens / Q000633:toxicity*; D014704:Veratrum Alkaloids / Q000633:toxicity; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics; D000097607:Homeobox Protein SIX3
D005576:Colforsin; D017931:DNA Primers; D000431:Ethanol; D005136:Eye Proteins; D051956:Goosecoid Protein; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D013723:Teratogens; D014704:Veratrum Alkaloids; D029961:Zebrafish Proteins; D000097607:Homeobox Protein SIX3; C497995:gsc protein, zebrafish; C509240:shhb protein, zebrafish; C000541:cyclopamine