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.
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.
Authors: Elizabeth A Godin; Deborah B Dehart; Scott E Parnell; Shonagh K O'Leary-Moore; Kathleen K Sulik Journal: Neurotoxicol Teratol Date: 2010-11-11 Impact factor: 3.763
Authors: Bhavani Kashyap; Laurel Pegorsch; Ruth A Frey; Chi Sun; Eric A Shelden; Deborah L Stenkamp Journal: Reprod Toxicol Date: 2013-12-16 Impact factor: 3.143
Authors: J M Bailey; A N Oliveri; C Zhang; J M Frazier; S Mackinnon; G J Cole; E D Levin Journal: Neurotoxicol Teratol Date: 2015-01-16 Impact factor: 3.763
Authors: Jan M Spitsbergen; Vicki S Blazer; Paul R Bowser; Keith C Cheng; Keith R Cooper; Timothy K Cooper; Salvatore Frasca; David B Groman; Claudia M Harper; Jerry M Mac Law; Gary D Marty; Roxanna M Smolowitz; Judy St Leger; Douglas C Wolf; Jeffrey C Wolf Journal: Comp Biochem Physiol C Toxicol Pharmacol Date: 2008-10-09 Impact factor: 3.228