RT Journal Article
SR Electronic
T1 Quantification of gene expression patterns to reveal the origins of abnormal morphogenesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 246256
DO 10.1101/246256
A1 N. Martínez-Abadías
A1 R. Mateu
A1 J. Sastre
A1 S Motch Perrine
A1 M Yoon
A1 A. Robert-Moreno
A1 J. Swoger
A1 L. Russo
A1 K Kawasaki
A1 J. Richtsmeier
A1 J. Sharpe
YR 2018
UL http://biorxiv.org/content/early/2018/01/11/246256.abstract
AB 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 can be obscured later in development due to secondary phenotypic effects. We here 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, our approach is sensitive enough to find regulatory abnormalities never previously detected. We identified subtle but significant differences in gene expression of a downstream target of the Fgfr2 mutation associated with Apert syndrome. Challenging previous reports, we demonstrate that Apert syndrome mouse models can further our understanding of limb defects in the human condition. Our method can be applied to other organ systems and models to investigate the etiology of malformations.