Geometric morphometrics on gene expression patterns within phenotypes: a case example on limb development

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• dc.contributor.author Martínez Abadías, Neusca
• dc.contributor.author Mateu-Estivill, Rogerca
• dc.contributor.author Niksic, Martinaca
• dc.contributor.author Russo, Luciaca
• dc.contributor.author Sharpe, Jamesca
• dc.date.accessioned 2016-06-08T13:25:32Z
• dc.date.available 2016-06-08T13:25:32Z
• dc.date.issued 2016
• dc.description.abstract How the genotype translates into the phenotype through development is critical to fully understand the evolution of phenotypes. We propose a novel approach to directly assess how changes in gene expression patterns are associated with changes in morphology using the limb as a case example. Our method combines molecular biology techniques, such as whole-mount in situ hybridization, with image and shape analysis, extending the use of Geometric Morphometrics to the analysis of nonanatomical shapes, such as gene expression domains. Elliptical Fourier and Procrustes-based semilandmark analyses were used to analyze the variation and covariation patterns of the limb bud shape with the expression patterns of two relevant genes for limb morphogenesis, Hoxa11 and Hoxa13. We devised a multiple thresholding method to semiautomatically segment gene domains at several expression levels in large samples of limb buds from C57Bl6 mouse embryos between 10 and 12 postfertilization days. Besides providing an accurate phenotyping tool to quantify the spatiotemporal dynamics of gene expression patterns within developing structures, our morphometric analyses revealed high, non-random, and gene-specific variation undergoing canalization during limb development. Our results demonstrate that Hoxa11 and Hoxa13, despite being paralogs with analogous functions in limb patterning, show clearly distinct dynamic patterns, both in shape and size, and are associated differently with the limb bud shape. The correspondence between our results and already well-established molecular processes underlying limb development confirms that this morphometric approach is a powerful tool to extract features of development regulating morphogenesis. Such multilevel analyses are promising in systems where not so much molecular information is available and will advance our understanding of the genotype-phenotype map. In systematics, this knowledge will increase our ability to infer how evolution modified a common developmental pattern to generate a wide diversity of morphologies, as in the vertebrate limb.ca
• dc.description.sponsorship The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement Beatriu de Pinós Grant 2010_BP_B_00183-1 and Marie Curie Fellowship FP7-PEOPLE-2012-IIF 327382. We acknowledge support of the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013-2017’, SEV-2012-0208.
• dc.format.mimetype application/pdfca
• dc.identifier.citation Martínez-Abadías N, Mateu R, Niksic M, Russo L, Sharpe J. Geometric morphometrics on gene expression patterns within phenotypes: a case example on limb development. Systematic biology. 2016; 65(2): 194-211. DOI 10.1093/sysbio/syv067ca
• dc.identifier.doi http://dx.doi.org/10.1093/sysbio/syv067
• dc.identifier.issn 1063-5157
• dc.identifier.uri http://hdl.handle.net/10230/26875
• dc.language.iso engca
• dc.publisher Oxford University Pressca
• dc.relation.ispartof Systematic biology. 2016; 65(2): 194-211
• dc.relation.ispartof info:eu-repo/grantAgreement/ES/3PN/SEV-2012-0208
• dc.relation.ispartof info:eu-repo/grantAgreement/EC/FP7/327382
• dc.rights © The Author(s) 2015. Published by Oxford University Press, on behalf of the Society of Systematic Biologists./nThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use,ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/ca
• dc.subject.keyword Elliptical Fourier analysis
• dc.subject.keyword Hoxa genes
• dc.subject.keyword Procrustes-based semilandmark
• dc.subject.keyword Gene domain
• dc.subject.keyword Limb morphogenesis
• dc.subject.keyword Whole-mount in situ hybridization
• dc.subject.other Morfogènesica
• dc.title Geometric morphometrics on gene expression patterns within phenotypes: a case example on limb developmentca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca