Metabolomic insights into system-wide coordination of vertebrate metamorphosis

dc.contributor.authorIchu, Taka-Aki
dc.contributor.authorHan, Jun
dc.contributor.authorBorchers, Christoph H.
dc.contributor.authorLesperance, Mary
dc.contributor.authorHelbing, Caren C.en
dc.date.accessioned2016-06-22T12:26:45Z
dc.date.available2016-06-22T12:26:45Z
dc.date.copyright2014en_US
dc.date.issued2014-02
dc.description.abstractBackground: 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.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipWe would like to thank Linghong Lu for helpful discussions. This work was funded by a Natural Sciences and Engineering Research Council (NSERC) Discovery grant to CH. TI was recipient of a UVic undergraduate research award. The MS analysis was performed at the University of Victoria - Genome BC Proteomics Centre, which is supported by the Genome Canada-funded “The Metabolomics Innovation Centre (TMIC)” for metabolomics research, and funding from Genome Canada and Genome British Columbia through the “Science and Technology Innovation Centre (S&TIC)”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.identifier.citationIchu, T-A., Han, J., Borchers, C.H., Lesperance, M. & Helbing, C.C. (2014). Metabolomic insights into system-wide coordination of vertebrate metamorphosis. BMC Developmental Biology, 14(5), 1-23.en_US
dc.identifier.urihttp://dx.doi.org/10.1186/1471-213X-14-5
dc.identifier.urihttp://hdl.handle.net/1828/7349
dc.language.isoenen_US
dc.publisherBMC Developmental Biologyen_US
dc.rightsAttribution 2.5 Canada*
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/ca/*
dc.subjectPostembryonic development
dc.subjectThyroid hormone
dc.subjectMetamorphosis
dc.subjectMetabolites
dc.subjectSerum
dc.subjectUltra-performance liquid chromatography
dc.subjectQuadrupole time-of-flight
dc.subjectMass spectrometry
dc.subjectVertebrate
dc.subjectUVic Genome BC Proteomics Centre
dc.subject.departmentDepartment of Biochemistry and Microbiology
dc.subject.departmentDepartment of Mathematics and Statistics
dc.titleMetabolomic insights into system-wide coordination of vertebrate metamorphosisen_US
dc.typeArticleen_US

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