Martinez-Abadias, NeusMateu Estivill, RogerSastre Tomas, JaumePerrine, Susan MotchYoon, MelissaRobert-Moreno, AlexandreSwoger, JimRusso, LuciaKawasaki, KazuhikoRichtsmeier, JoanSharpe, James2024-09-062024-09-062018-09-20Martinez-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:e36405.2050-084Xhttp://hdl.handle.net/20.500.13003/9120https://hdl.handle.net/20.500.12105/22556The 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.enghttp://creativecommons.org/licenses/by/4.0/Disease Models, AnimalBiometryGene Expression Regulation, DevelopmentalGene Expression ProfilingAnimalsReceptor, Fibroblast Growth Factor, Type 2Tomography, X-Ray ComputedAcrocephalosyndactyliaMice, Inbred C57BLMutation, Missenseresearch articleAttribution 4.0 International302344867e3640510.7554/eLife.36405Elifeopen accessAnimalesTomografía Computarizada por Rayos XMutación MissenseAcrocefalosindactiliaRatones Endogámicos C57BLBiometríaRegulación del Desarrollo de la Expresión GénicaPerfilación de la Expresión GénicaModelos Animales de EnfermedadReceptor Tipo 2 de Factor de Crecimiento de Fibroblastos2-s2.0-85055138079447963100001L625390081