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

ELife
Neus Martínez-AbadíasJames Sharpe

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.

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Citations

Dec 19, 2018·Journal of Developmental Biology·Kevin Flaherty, Joan T Richtsmeier
May 24, 2019·Integrative and Comparative Biology·Ryan N FeliceAnjali Goswami
Apr 29, 2020·Biomedical Optics Express·Shang WangKirill V Larin

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Methods Mentioned

BETA
PCA
X-ray
PCR
genotyping

Software Mentioned

Amira
Excel
GM
R package geomorph
MorphoJ
Generalized Procrustes Analysis ( GPA )
R R Development Core Team
SPSS Statistics
Matlab
OPT

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