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oai:repisalud.isciii.es:20.500.12105/225562024-11-28T20:26:20Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Martinez-Abadias, Neus author Mateu Estivill, Roger author Sastre Tomas, Jaume author Perrine, Susan Motch author Yoon, Melissa author Robert-Moreno, Alexandre author Swoger, Jim author Russo, Lucia author Kawasaki, Kazuhiko author Richtsmeier, Joan author Sharpe, James author 2018-09-20 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. Martinez-Abadias 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 Sep 20;7:e36405. 10.7554/eLife.36405 2050-084X Elife http://hdl.handle.net/20.500.13003/9120 30234486 L625390081 2-s2.0-85055138079 https://hdl.handle.net/20.500.12105/22556 447963100001 Quantification of gene expression patterns to reveal the origins of abnormal morphogenesis