title: Coordinated gene expression during gilthead sea bream skeletogenesis and its disruption by nutritional hypervitaminosis A.
abstract: 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 β-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 α1 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.affiliation: Unitat de Cultius Experimentals, IRTA Centre de Sant Carles de la Ràpita (IRTA-SCR), Crta, del Poble Nou s/n, 43540 - Sant Carles de la Ràpita (Spain) ignacio.fernandez@irta.es
authors.forename: Ignacio
authors.initials: I
authors.lastname: Fernández
authors.forename: Maria
authors.initials: M
authors.lastname: Darias
authors.forename: Karl B
authors.initials: KB
authors.lastname: Andree
authors.forename: David
authors.initials: D
authors.lastname: Mazurais
authors.forename: Jose Luís
authors.initials: JL
authors.lastname: Zambonino-Infante
authors.forename: Enric
authors.initials: E
authors.lastname: Gisbert
mesh_terms: D000818:Animals; D001846:Bone Development; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D016326:Extracellular Matrix Proteins / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006986:Hypervitaminosis A / Q000235:genetics; D009024:Morphogenesis; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics; D047488:Retinoid X Receptors / Q000235:genetics; D012177:Retinol-Binding Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021541:Sea Bream / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D013002:Somatomedins / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D014212:Tretinoin / Q000378:metabolism*; D014801:Vitamin A / Q000008:administration & dosage*
chemical_list: D055396:Bone Morphogenetic Protein 2; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D016326:Extracellular Matrix Proteins; D047492:Peroxisome Proliferator-Activated Receptors; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012177:Retinol-Binding Proteins; D013002:Somatomedins; D016212:Transforming Growth Factor beta; D014801:Vitamin A; D014212:Tretinoin