title: Transcriptional responses of zebrafish embryos exposed to potential sonic hedgehog pathway interfering compounds deviate from expression profiles of cyclopamine.
abstract: The molecular responses of two small molecules, SANT-2 and GANT-61, potentially interfering with the sonic hedgehog pathway (Shh) have been studied in zebrafish embryos by microarray analysis. For both compounds and the positive reference cyclopamine previous reporter gene assays for the transcription factor Gli1 have indicated an inhibition of the hedgehog signaling pathway. In zebrafish embryos a typical phenotype (cyclopia) associated with Shh interference was only observed for cyclopamine. Furthermore, only cyclopamine led to the repression of genes specifically associated with hedgehog signaling and confirmed published microarray data. In contrast to these data hspb11 was additionally identified as the most pronounced down-regulated genes for exposure to cyclopamine. No or different effects on gene expression patterns were provoked by SANT-2 or GANT-61, respectively. Reasons for the discrepancies between cellular reporter and the zebrafish embryo assay and potential implications for the identification of compounds interfering with specific developmental pathways are discussed.
authors.affiliation: University of Leipzig, Institute of Organic Chemistry, Johannisallee 29, 04103 Leipzig, Germany. anita.buettner@gmx.de
authors.forename: Anita
authors.initials: A
authors.lastname: Büttner
authors.forename: Wibke
authors.initials: W
authors.lastname: Busch
authors.forename: Nils
authors.initials: N
authors.lastname: Klüver
authors.forename: Athanassios
authors.initials: A
authors.lastname: Giannis
authors.forename: Stefan
authors.initials: S
authors.lastname: Scholz
mesh_terms: D000818:Animals; D001549:Benzamides / Q000633:toxicity*; D001562:Benzimidazoles / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D053823:Hedgehog Proteins / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000235:genetics; D011725:Pyridines / Q000633:toxicity*; D011743:Pyrimidines / Q000633:toxicity*; D014158:Transcription, Genetic; D014704:Veratrum Alkaloids / Q000633:toxicity*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D001549:Benzamides; D001562:Benzimidazoles; C551027:GANT 61; D053823:Hedgehog Proteins; D011725:Pyridines; D011743:Pyrimidines; C468920:SANT-2 compound; D014704:Veratrum Alkaloids; D029961:Zebrafish Proteins; C000541:cyclopamine