Transcriptional regulation of genes involved in retinoic acid metabolism in Senegalese sole larvae.
The aim of this study was the characterization of transcriptional regulatory pathways mediated by retinoic acid (RA) in Senegalese sole larvae. For this purpose, pre-metamorphic larvae were treated with a low concentration of DEAB, an inhibitor of RALDH enzyme, until the end of metamorphosis. No differences in growth, eye migration or survival were observed. Nevertheless, gene expression analysis revealed a total of 20 transcripts differentially expressed during larval development and only six related with DEAB treatments directly involved in RA metabolism and actions (rdh10a, aldh1a2, crbp1, igf2r, rarg and cyp26a1) to adapt to a low-RA environment. In a second experiment, post-metamorphic larvae were exposed to the all-trans RA (atRA) observing an opposite regulation for those genes involved in RA synthesis and degradation (rdh10a, aldh1a2, crbp1 and cyp26a1) as well as other related with thyroid- (dio2) and IGF-axes (igfbp1, igf2r and igfbp5) to balance RA levels. In a third experiment, DEAB-pretreated post-metamorphic larvae were exposed to atRA and TTNPB (a specific RAR agonist). Both drugs down-regulated rdh10a and aldh1a2 and up-regulated cyp26a1 expression demonstrating their important role in RA homeostasis. Moreover, five retinoic receptors that mediate RA actions, the thyroid receptor thrb, and five IGF binding proteins changed differentially their expression. Overall, this study demonstrates that exogenous RA modulates the expression of some genes involved in the RA synthesis, degradation and cellular transport through RAR-mediated regulatory pathways establishing a negative feedback regulatory mechanism necessary to balance endogenous RA levels and gradients.
Centro de Investigación en Alimentación y Desarrollo, Unidad Mazatlán (CIAD), PO Box 711, 82010 Mazatlán, Sinaloa, Mexico.
Anaïs
A
Boglino
IFAPA Centro El Toruño, Junta de Andalucía, Camino Tiro de Pichón s/n, 11500 El Puerto de Santa María, Cádiz, Spain.
Marian
M
Ponce
IFREMER, Laboratoire d'Ecotoxicologie, Place Gaby Coll, BP7, 17137 L'Houmeau, France.
Xavier
X
Cousin
IRTA-Sant Carles de la Ràpita, Ctra. De Poble Nou km 5.5, 43540 Sant Carles de la Ràpita, Tarragona, Spain.
Enric
E
Gisbert
IFAPA Centro El Toruño, Junta de Andalucía, Camino Tiro de Pichón s/n, 11500 El Puerto de Santa María, Cádiz, Spain. Electronic address: manuel.manchado@juntadeandalucia.es.
Manuel
M
Manchado
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D005412:Flatfishes / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D007814:Larva / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D008675:Metamorphosis, Biological / Q000187:drug effects / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology; D014212:Tretinoin / Q000378:metabolism*; D010128:p-Aminoazobenzene / Q000031:analogs & derivatives / Q000494:pharmacology
D001565:Benzoates; D018168:Receptors, Retinoic Acid; D012176:Retinoids; C007368:C.I. Solvent Yellow 56; D014212:Tretinoin; D010128:p-Aminoazobenzene; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid
Gene expression; Larvae; Regulation pathways; Retinoic acid; Senegalese sole