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

Fernández I, Darias M, Andree KB, Mazurais D, Zambonino-Infante JL, Gisbert E - BMC Dev. Biol. (2011)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

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

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.

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Related in: MedlinePlus

Hierarchical clustering of the 16 target genes analysed based on mRNA expression, showing the cluster of the different studied genes with similar expression profile during larval development. Columns represent the mean data values for each of the 10 sampling times (days post hatching; dph) and rows represent single genes. Expression level of each gene is represented relative to its median abundance across the different stages and is depicted by a colour scale: green, black, and red indicating low, medium, and high relative expression levels, respectively. Coloured bars to the right indicate the location of two gene clusters: red corresponds to genes with a progressive increase in mean gene expression level from 2 to 60 dph; and green with those whose mean gene expression level decreased progressively from an initial relative high level of expression.
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Figure 7: Hierarchical clustering of the 16 target genes analysed based on mRNA expression, showing the cluster of the different studied genes with similar expression profile during larval development. Columns represent the mean data values for each of the 10 sampling times (days post hatching; dph) and rows represent single genes. Expression level of each gene is represented relative to its median abundance across the different stages and is depicted by a colour scale: green, black, and red indicating low, medium, and high relative expression levels, respectively. Coloured bars to the right indicate the location of two gene clusters: red corresponds to genes with a progressive increase in mean gene expression level from 2 to 60 dph; and green with those whose mean gene expression level decreased progressively from an initial relative high level of expression.

Mentions: Global hierarchical clustering was applied on the gene expression ratios during larval development for the 16 studied genes (Figure 7). This clustering was used to classify genes on the basis of similarity of their expression profile during larval development sampling times. Two gene clusters were found: (i) genes whose mean gene expression level increased from 37 dph, such as IGF1, TGFB1, RXRB, IGF2 and genes encoding extracellular matrix proteins (mgp, bglap, SPP1, SPARC and COL1A1); and (ii) genes whose mean gene expression ratio decreased progressively from an initial relatively high level of expression (PPARB, RARA and RBP).


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

Fernández I, Darias M, Andree KB, Mazurais D, Zambonino-Infante JL, Gisbert E - BMC Dev. Biol. (2011)

Hierarchical clustering of the 16 target genes analysed based on mRNA expression, showing the cluster of the different studied genes with similar expression profile during larval development. Columns represent the mean data values for each of the 10 sampling times (days post hatching; dph) and rows represent single genes. Expression level of each gene is represented relative to its median abundance across the different stages and is depicted by a colour scale: green, black, and red indicating low, medium, and high relative expression levels, respectively. Coloured bars to the right indicate the location of two gene clusters: red corresponds to genes with a progressive increase in mean gene expression level from 2 to 60 dph; and green with those whose mean gene expression level decreased progressively from an initial relative high level of expression.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3045981&req=5

Figure 7: Hierarchical clustering of the 16 target genes analysed based on mRNA expression, showing the cluster of the different studied genes with similar expression profile during larval development. Columns represent the mean data values for each of the 10 sampling times (days post hatching; dph) and rows represent single genes. Expression level of each gene is represented relative to its median abundance across the different stages and is depicted by a colour scale: green, black, and red indicating low, medium, and high relative expression levels, respectively. Coloured bars to the right indicate the location of two gene clusters: red corresponds to genes with a progressive increase in mean gene expression level from 2 to 60 dph; and green with those whose mean gene expression level decreased progressively from an initial relative high level of expression.
Mentions: Global hierarchical clustering was applied on the gene expression ratios during larval development for the 16 studied genes (Figure 7). This clustering was used to classify genes on the basis of similarity of their expression profile during larval development sampling times. Two gene clusters were found: (i) genes whose mean gene expression level increased from 37 dph, such as IGF1, TGFB1, RXRB, IGF2 and genes encoding extracellular matrix proteins (mgp, bglap, SPP1, SPARC and COL1A1); and (ii) genes whose mean gene expression ratio decreased progressively from an initial relatively high level of expression (PPARB, RARA and RBP).

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

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

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.

Show MeSH
Related in: MedlinePlus