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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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Ontogenetic gene expression patterns of mgp (a), bglap (b), SPP1 (c), SPARC (d), and COL1A1 (e). Gene expression measured as the mean expression ratio of the target gene respect to the house-keeping gene (EF1α) at each sample time compared with initial sample time (2 dph). Different letters denote significant differences of the global gene expression (ANOVA, P < 0.05; n = 3).
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Figure 6: Ontogenetic gene expression patterns of mgp (a), bglap (b), SPP1 (c), SPARC (d), and COL1A1 (e). Gene expression measured as the mean expression ratio of the target gene respect to the house-keeping gene (EF1α) at each sample time compared with initial sample time (2 dph). Different letters denote significant differences of the global gene expression (ANOVA, P < 0.05; n = 3).

Mentions: With respect to the expression patterns of genes encoding ECM proteins during larval development, all of them increased at the end of the study. However, the mean gene expression ratios reached at the end of the experiment by each gene were different. The genes mgp and bglap showed the highest mean expression ratios at 60 dph (199.38 and 7956.15, respectively; ANOVA, P < 0.05; Figure 6a,b). In both Gla protein genes, a significant increase in the mean gene expression ratio was observed near the end of the trial (around 45 dph). In contrast, SPP1 and SPARC showed lower mean values (23.38 and 3.25, respectively) at the end of the experiment (Figure 6c and 6d, respectively) compared with mgp and bglap ratios, although presenting significant increases as well in comparison to results from early larval stages (ANOVA, P < 0.05). Furthermore, both SPP1 and SPARC showed a significant increase at 37 dph in their mean gene expression ratios, earlier than mgp and bglap. Finally, COL1A1 presented a similar gene expression profile to those of other ECM protein genes, with a significant increase in the mean gene expression ratio at 60 dph (ANOVA, P < 0.05; Figure 6e).


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)

Ontogenetic gene expression patterns of mgp (a), bglap (b), SPP1 (c), SPARC (d), and COL1A1 (e). Gene expression measured as the mean expression ratio of the target gene respect to the house-keeping gene (EF1α) at each sample time compared with initial sample time (2 dph). Different letters denote significant differences of the global gene expression (ANOVA, P < 0.05; n = 3).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Ontogenetic gene expression patterns of mgp (a), bglap (b), SPP1 (c), SPARC (d), and COL1A1 (e). Gene expression measured as the mean expression ratio of the target gene respect to the house-keeping gene (EF1α) at each sample time compared with initial sample time (2 dph). Different letters denote significant differences of the global gene expression (ANOVA, P < 0.05; n = 3).
Mentions: With respect to the expression patterns of genes encoding ECM proteins during larval development, all of them increased at the end of the study. However, the mean gene expression ratios reached at the end of the experiment by each gene were different. The genes mgp and bglap showed the highest mean expression ratios at 60 dph (199.38 and 7956.15, respectively; ANOVA, P < 0.05; Figure 6a,b). In both Gla protein genes, a significant increase in the mean gene expression ratio was observed near the end of the trial (around 45 dph). In contrast, SPP1 and SPARC showed lower mean values (23.38 and 3.25, respectively) at the end of the experiment (Figure 6c and 6d, respectively) compared with mgp and bglap ratios, although presenting significant increases as well in comparison to results from early larval stages (ANOVA, P < 0.05). Furthermore, both SPP1 and SPARC showed a significant increase at 37 dph in their mean gene expression ratios, earlier than mgp and bglap. Finally, COL1A1 presented a similar gene expression profile to those of other ECM protein genes, with a significant increase in the mean gene expression ratio at 60 dph (ANOVA, P < 0.05; Figure 6e).

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