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Metabolomic insights into system-wide coordination of vertebrate metamorphosis.

Ichu TA, Han J, Borchers CH, Lesperance M, Helbing CC - BMC Dev. Biol. (2014)

Bottom Line: The majority of the detected metabolites (74%) showed statistically significant abundance changes (padj < 0.001) between metamorphic stages.We observed extensive remodelling of five core metabolic pathways: arginine and purine/pyrimidine, cysteine/methionine, sphingolipid, and eicosanoid metabolism and the urea cycle, and found evidence for a major role for lipids during this postembryonic process.Metabolites traditionally linked to human disease states were found to have biological linkages to the system-wide changes occuring during the events leading up to overt morphological change.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8W 2Y2, Canada. chelbing@uvic.ca.

ABSTRACT

Background: After completion of embryogenesis, many organisms experience an additional obligatory developmental transition to attain a substantially different juvenile or adult form. During anuran metamorphosis, the aquatic tadpole undergoes drastic morphological changes and remodelling of tissues and organs to become a froglet. Thyroid hormones are required to initiate the process, but the mechanism whereby the many requisite changes are coordinated between organs and tissues is poorly understood. Metabolites are often highly conserved biomolecules between species and are the closest reflection of phenotype. Due to the extensive distribution of blood throughout the organism, examination of the metabolites contained therein provides a system-wide overview of the coordinated changes experienced during metamorphosis. We performed an untargeted metabolomic analysis on serum samples from naturally-metamorphosing Rana catesbeiana from tadpoles to froglets using ultraperformance liquid chromatography coupled to a mass spectrometer. Total and aqueous metabolite extracts were obtained from each serum sample to select for nonpolar and polar metabolites, respectively, and selected metabolites were validated by running authentic compounds.

Results: The majority of the detected metabolites (74%) showed statistically significant abundance changes (padj < 0.001) between metamorphic stages. We observed extensive remodelling of five core metabolic pathways: arginine and purine/pyrimidine, cysteine/methionine, sphingolipid, and eicosanoid metabolism and the urea cycle, and found evidence for a major role for lipids during this postembryonic process. Metabolites traditionally linked to human disease states were found to have biological linkages to the system-wide changes occuring during the events leading up to overt morphological change.

Conclusions: To our knowledge, this is the first wide-scale metabolomic study of vertebrate metamorphosis identifying fundamental pathways involved in the coordination of this important developmental process and paves the way for metabolomic studies on other metamorphic systems including fish and insects.

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Boxplots of metabolites in urea cycle, arginine and purine/pyrimidine metabolism pathway.
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Figure 5: Boxplots of metabolites in urea cycle, arginine and purine/pyrimidine metabolism pathway.

Mentions: During metamorphosis, tadpoles undergo a fasting period during which energy is provided by muscle breakdown of the tail [19,20]. Creatine acts as an energy shuttle of ATP between the mitochondrial sites of ATP production and the cytosolic sites of ATP utilization [21]. 3-methylhistidine has been shown to be a marker of muscle breakdown [22]. Both creatine and 3-methylhistidine showed a significant decrease at the froglet stage (Figures 3, 5 and 6), which correlates with the energy requirement of tadpoles during metamorphosis.


Metabolomic insights into system-wide coordination of vertebrate metamorphosis.

Ichu TA, Han J, Borchers CH, Lesperance M, Helbing CC - BMC Dev. Biol. (2014)

Boxplots of metabolites in urea cycle, arginine and purine/pyrimidine metabolism pathway.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3928663&req=5

Figure 5: Boxplots of metabolites in urea cycle, arginine and purine/pyrimidine metabolism pathway.
Mentions: During metamorphosis, tadpoles undergo a fasting period during which energy is provided by muscle breakdown of the tail [19,20]. Creatine acts as an energy shuttle of ATP between the mitochondrial sites of ATP production and the cytosolic sites of ATP utilization [21]. 3-methylhistidine has been shown to be a marker of muscle breakdown [22]. Both creatine and 3-methylhistidine showed a significant decrease at the froglet stage (Figures 3, 5 and 6), which correlates with the energy requirement of tadpoles during metamorphosis.

Bottom Line: The majority of the detected metabolites (74%) showed statistically significant abundance changes (padj < 0.001) between metamorphic stages.We observed extensive remodelling of five core metabolic pathways: arginine and purine/pyrimidine, cysteine/methionine, sphingolipid, and eicosanoid metabolism and the urea cycle, and found evidence for a major role for lipids during this postembryonic process.Metabolites traditionally linked to human disease states were found to have biological linkages to the system-wide changes occuring during the events leading up to overt morphological change.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8W 2Y2, Canada. chelbing@uvic.ca.

ABSTRACT

Background: After completion of embryogenesis, many organisms experience an additional obligatory developmental transition to attain a substantially different juvenile or adult form. During anuran metamorphosis, the aquatic tadpole undergoes drastic morphological changes and remodelling of tissues and organs to become a froglet. Thyroid hormones are required to initiate the process, but the mechanism whereby the many requisite changes are coordinated between organs and tissues is poorly understood. Metabolites are often highly conserved biomolecules between species and are the closest reflection of phenotype. Due to the extensive distribution of blood throughout the organism, examination of the metabolites contained therein provides a system-wide overview of the coordinated changes experienced during metamorphosis. We performed an untargeted metabolomic analysis on serum samples from naturally-metamorphosing Rana catesbeiana from tadpoles to froglets using ultraperformance liquid chromatography coupled to a mass spectrometer. Total and aqueous metabolite extracts were obtained from each serum sample to select for nonpolar and polar metabolites, respectively, and selected metabolites were validated by running authentic compounds.

Results: The majority of the detected metabolites (74%) showed statistically significant abundance changes (padj < 0.001) between metamorphic stages. We observed extensive remodelling of five core metabolic pathways: arginine and purine/pyrimidine, cysteine/methionine, sphingolipid, and eicosanoid metabolism and the urea cycle, and found evidence for a major role for lipids during this postembryonic process. Metabolites traditionally linked to human disease states were found to have biological linkages to the system-wide changes occuring during the events leading up to overt morphological change.

Conclusions: To our knowledge, this is the first wide-scale metabolomic study of vertebrate metamorphosis identifying fundamental pathways involved in the coordination of this important developmental process and paves the way for metabolomic studies on other metamorphic systems including fish and insects.

Show MeSH
Related in: MedlinePlus