Quantification of gene expression patterns to reveal the origins of abnormal morphogenesis

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• dc.contributor.author Martínez Abadías, Neus
• dc.contributor.author Mateu-Estivill, Roger
• dc.contributor.author Sastre-Tomas, Jaume
• dc.contributor.author Motch Perrine, Susan
• dc.contributor.author Yoon, Melissa
• dc.contributor.author Robert Moreno, Alexandre
• dc.contributor.author Swoger, Jim
• dc.contributor.author Russo, Lucia
• dc.contributor.author Kawasaki, Kazuhiko
• dc.date.accessioned 2019-11-13T11:18:51Z
• dc.date.available 2019-11-13T11:18:51Z
• dc.date.issued 2018
• dc.description.abstract The earliest developmental origins of dysmorphologies are poorly understood in many congenital diseases. They often remain elusive because the first signs of genetic misregulation may initiate as subtle changes in gene expression, which are hard to detect and can be obscured later in development by secondary effects. Here, we develop a method to trace back the origins of phenotypic abnormalities by accurately quantifying the 3D spatial distribution of gene expression domains in developing organs. By applying Geometric Morphometrics to 3D gene expression data obtained by Optical Projection Tomography, we determined that our approach is sensitive enough to find regulatory abnormalities that have never been detected previously. We identified subtle but significant differences in the gene expression of a downstream target of a Fgfr2 mutation associated with Apert syndrome, demonstrating that these mouse models can further our understanding of limb defects in the human condition. Our method can be applied to different organ systems and models to investigate the etiology of malformations.
• dc.description.sponsorship The research leading to these results received funding from the following grants: a European Union Seventh Framework Program (FP7/2007-2013) under grant agreement Marie Curie Fellowship FP7-PEOPLE-2012-IIF 327382, National Institutes of Health grants NICHD P01HD078233 and NIDCR R01DE02298, and a Burroughs-Welcome Fund 2013 Collaborative Research Travel Grant.
• dc.format.mimetype application/pdf
• dc.identifier.citation Martínez-Abadías N, Mateu Estivill R, Sastre Tomas J, Motch Perrine S, Yoon M, Robert-Moreno A et al. Quantification of gene expression patterns to reveal the origins of abnormal morphogenesis. eLife. 2018;7:e36405. DOI: 10.7554/eLife.36405
• dc.identifier.doi http://dx.doi.org/10.7554/eLife.36405
• dc.identifier.issn 2050-084X
• dc.identifier.uri http://hdl.handle.net/10230/42839
• dc.language.iso eng
• dc.publisher eLife
• dc.relation.ispartof eLife. 2018;7:e36405
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/327382
• dc.rights © 2018, Martínez-Abadías et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Apert syndrome
• dc.subject.keyword Geometric Morphometrics (GM)
• dc.subject.keyword Optical Projection Tomography (OPT)
• dc.subject.keyword Developmental biology
• dc.subject.keyword Developmental defects
• dc.subject.keyword Limb development
• dc.subject.keyword Mouse
• dc.subject.keyword Whole‐mount‐in‐situ hybridization (WMISH)
• dc.title Quantification of gene expression patterns to reveal the origins of abnormal morphogenesis
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion