Format

Send to

Choose Destination
Elife. 2018 Sep 20;7. pii: e36405. doi: 10.7554/eLife.36405.

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

Author information

1
Centre for Genomic Regulation, The Barcelona Institute for Science and Technology, Barcelona, Spain.
2
Universitat Pompeu Fabra, Barcelona, Spain.
3
EMBL Barcelona, European Molecular Biology Laboratory, Barcelona, Spain.
4
Universitat de Barcelona, Barcelona, Spain.
5
Universitat de les Illes Balears (UIB), Palma de Mallorca, Spain.
6
Pennsylvania State University, Pennsylvania, United States.
7
Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.

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.

KEYWORDS:

Apert syndrome; Geometric Morphometrics (GM); Optical Projection Tomography (OPT); developmental biology; developmental defects; limb development; mouse; whole‐mount‐in‐situ hybridization (WMISH)

PMID:
30234486
PMCID:
PMC6199133
DOI:
10.7554/eLife.36405
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center