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Coordinated gene expression during gilthead sea bream skeletogenesis and its disruption by nutritional hypervitaminosis A Fernández, Ignacio Darias, Maria Andree, Karl Mazurais, David Zambonino-Infante, Jose Luís Gisbert, Enric Producció Animal Aqüicultura 63 Background: Vitamin A (VA) has a key role in vertebrate morphogenesis, determining body patterning and growth through the control of cell proliferation and differentiation processes. VA regulates primary molecular pathways of those processes by the binding of its active metabolite (retinoic acid) to two types of specific nuclear receptors: retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which promote transcription of downstream target genes. This process is well known in most of higher vertebrates; however, scarce information is available regarding fishes. Therefore, in order to gain further knowledge of fish larval development and its disruption by nutritional VA imbalance, the relative expression of some RARs and RXRs, as well as several genes involved in morpho- and skeletogenesis such as peroxisome proliferator-activated receptors (PPARA, PPARB and PPARG); retinol-binding protein (RBP); insulin-like growth factors I and II (IGF1 and IGF2, respectively); bone morphogenetic protein 2 (Bmp2); transforming growth factor b-1 (TGFB1); and genes encoding different extracellular matrix (ECM) proteins such as matrix Gla protein (mgp), osteocalcin (bglap), osteopontin (SPP1), secreted protein acidic and rich in cysteine (SPARC) and type I collagen a1 chain (COL1A1) have been studied in gilthead sea bream. Results: During gilthead sea bream larval development, specific expression profiles for each gene were tightly regulated during fish morphogenesis and correlated with specific morphogenetic events and tissue development. Dietary hypervitaminosis A during early larval development disrupted the normal gene expression profile for genes involved in RA signalling (RARA), VA homeostasis (RBP) and several genes encoding ECM proteins that are linked to skeletogenesis, such as bglap and mgp. Conclusions: Present data reflects the specific gene expression patterns of several genes involved in larval fish RA signalling and skeletogenesis; and how specific gene disruption induced by a nutritional VA imbalance underlie the skeletal deformities. Our results are of basic interest for fish VA signalling and point out some of the potential molecular players involved in fish skeletogenesis. Increased incidences of skeletal deformities in gilthead sea bream fed with hypervitaminosis A were the likely ultimate consequence of specific gene expression disruption at critical development stages. Authors are greatly indebted to the technical staff of IRTA-Sant Carles research centre for their excellent technical assistance during larvae trials with gilthead seabream, especially to M. Monllaó, and J. Canoura; as well as B. Desbruyères from IFREMER-Brest research centre for its technical assistance in bone mineralization analysis. Funding was provided to EG by the Ministry of Science and Innovation of the Spanish Government (MINCINN, projects AGL2005-02478, HF2008-0079 and AGL2008-03897-C04- 01). I.F was supported by a predoctoral fellowship (reference BES-2006- 12650). info:eu-repo/semantics/publishedVersion 2011-02-09 info:eu-repo/semantics/article Fernández, Ignacio, María J. Darias, Karl B. Andrée, David Mazurais, José‐Luis Zambonino-Infante, and Enric Gisbert. 2011. “Coordinated Gene Expression During Gilthead Sea Bream Skeletogenesis and Its Disruption by Nutritional Hypervitaminosis A.” BMC Developmental Biology 11 (1): 7. doi: 10.1186/1471-213x-11-7 1471-213X http://hdl.handle.net/20.500.12327/2980 https://doi.org/10.1186/1471-213X-11-7 eng BMC Developmental Biology MEC/Programa Nacional de Potenciación de Recursos Humanos/AGL2005-02478/ES/ / MICINN/Programa Nacional de Internacionalización de la I+D/HF2008-0079/ES/The role of dietary lipids on fish larvae quality: effects on skeletogenesis and pigmentation/ MICINN/Programa Nacional de Proyectos de Investigación Fundamental/AGL2008-03897-C04-01/ES/EL PAPEL DE LOS LIPIDOS SOBRE LA CALIDAD DE LARVAS DE PECES: EFECTOS SOBRE DEFORMACIONES ESQUELETICAS Y PROBLEMAS PIGMENARIOS/ Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess 20 BMC