Coordinated gene expression during gilthead sea bream skeletogenesis and its disruption by nutritional hypervitaminosis A

Abstract

BackgroundVitamin 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.ResultsDuring 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.ConclusionsPresent 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.

Transient up- and down-regulation of expression of myosin light chain 2 and myostatin mRNA mark the changes from stratified hyperplasia to muscle fiber hypertrophy in larvae of gilthead sea bream (Sparus aurata L.)

“…The rise in col1a1 expression at 35 dph was consistent with earlier results in the gilthead sea bream, in which col1a1 expression was low up to 29 dph and was significantly upregulated between 29-37 dph (Fernández et al 2011). A similar expression pattern was also observed during European sea bass development whereby col1a1 expression was positively correlated with bone development (Darias et al 2008) suggesting that col1a1 is of huge biological importance by providing mechanical support in both the growing skeleton and the increasing muscle fiber organization.…”

Vitamin A effects on vertebral bone tissue homeostasis in gilthead sea bream (Sparus aurata) juveniles

“…(2001), their gene expression results support our findings of OC protein accumulation in the notochord. Moreover, the increased OC and MGP protein accumulation in gilthead sea bream juveniles fed with hypervitaminosis A was in agreement with its higher gene expression in gilthead sea bream larvae fed with high dietary VA doses (Fernández et al., 2011). These results correlated with previous studies showing increased co‐transcription of both chondrogenic and osteogenic markers in the notochord of Atlantic salmon during the pathogenesis of spinal fusions (Ytteborg et al., 2010a,b).…”

Valproic Acid Downregulates RBP4 and Elicits Hypervitaminosis A-Teratogenesis—A Kinetic Analysis on Retinol/Retinoic Acid Homeostatic System

“…Hypervitaminosis A is likely to ultimately cause specific gene expression disruption at critical development stages [48]. A recent report has indicated that a high dietary intake of retinol can lead to bone marrow hypoxia and diaphyseal endosteal mineralization in rats [49].…”