Quantification of gene expression patterns to reveal the origins of abnormal morphogenesis
- The Barcelona Institute for Science and Technology, Spain
- Universitat de Barcelona, Spain
- Universitat de les Illes Balears, Spain
- Pennsylvania State University, United States
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 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 the Fgfr2 mutation that were 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.
Data availability
Our dataset has been deposited to Dryad (doi:10.5061/dryad.8h646s0)
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Data from: Quantification of gene expression patterns to reveal the origins of abnormal morphogenesisAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
Article and author information
Author details
Neus Martínez-Abadías
Roger Mateu Estivill
Jaume Sastre Tomas
Alex Robert-Moreno
Funding
European Commission (FP7‐PEOPLE‐2012‐ 597 IIF 327382)
- Neus Martínez-Abadías
National Institute for Health Research (NICHD P01HD078233)
- Joan Richtsmeier
National Institute for Health Research (NIDCR R01DE02298)
- Joan Richtsmeier
Burroughs Wellcome Fund (2013 Collaborative Research Travel Grant)
- Joan Richtsmeier
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All the experiments were performed in compliance with the animal welfare guidelines approved by the Pennsylvania State University Animal Care and Use Committees (IACUC46558, IBC46590).
Copyright
© 2018, Martínez-Abadías et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Quantification of gene expression patterns to reveal the origins of abnormal morphogenesis
eLife 7:e36405.
https://doi.org/10.7554/eLife.36405
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