title: Gene expression in Xenopus laevis embryos after Triadimefon exposure.
abstract: The triazole derivative Triadimefon (FON) is a systemic fungicide used to control powdery mildews, rusts, and other fungal pests. Some data have already been published about the teratogenic activity of this compound: craniofacial malformations were found in mouse, rat, and Xenopus laevis embryos exposed to FON. These alterations were correlated to defective branchial arch development possibly caused by abnormal neural crest cell (NCC) migration into the branchial mesenchyme. As the migration of NCCs is controlled by the HOX code and by an anteroposterior retinoic acid (RA) gradient, we analyzed the expression of CYP26, a key enzyme in RA metabolism, following FON exposure. The increased expression of this gene and the ability of citral (a RA inhibitor) to reduce the teratogenic effects of the fungicide support the notion that endogenous RA is involved in the mechanism of action of FON. Moreover, by in situ hybridization, we studied the effects of FON exposure at gastrula stage on the expression of some genes involved in craniofacial development, hindbrain patterning, and NCC migration. We observed abnormal localization of xCRABP, Hoxa2 and Xbap signal expression at the level of migrating NCC domains, whereas in the hindbrain, we did not find any alteration in Krox20 and Hoxa2 expression.
authors.affiliation: Department of Biotechnology and Molecular Science, University of Insubria, via Dunant 3, 21100 Varese, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Papis
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bernardini
authors.forename: Rosalba
authors.initials: R
authors.lastname: Gornati
authors.forename: Elena
authors.initials: E
authors.lastname: Menegola
authors.forename: Mariangela
authors.initials: M
authors.lastname: Prati
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005659:Fungicides, Industrial / Q000633:toxicity*; D005775:Gastrula / Q000187:drug effects / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D018398:Homeodomain Proteins / Q000235:genetics; D017403:In Situ Hybridization; D009432:Neural Crest / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics; D000072516:Retinoic Acid 4-Hydroxylase; D013723:Teratogens / Q000633:toxicity; D014157:Transcription Factors / Q000235:genetics; D014212:Tretinoin / Q000378:metabolism; D014230:Triazoles / Q000633:toxicity*; D029867:Xenopus Proteins / Q000235:genetics; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism
chemical_list: D005659:Fungicides, Industrial; D018398:Homeodomain Proteins; C489830:Hoxa2 protein, Xenopus; C104164:NKX3-2 protein, Xenopus; D018168:Receptors, Retinoic Acid; D013723:Teratogens; D014157:Transcription Factors; D014230:Triazoles; D029867:Xenopus Proteins; C032910:triadimefon; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase