Format

Send to

Choose Destination
Nature. 2018 Mar 22;555(7697):463-468. doi: 10.1038/nature26002. Epub 2018 Mar 14.

Placentation defects are highly prevalent in embryonic lethal mouse mutants.

Author information

1
The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
2
Centre for Trophoblast Research, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
3
The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
4
Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
5
Division of Anatomy, Center for Anatomy & Cell Biology, Medical University of Vienna, Waehringerstrasse 13, A-1090 Vienna, Austria.
6
Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
7
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.

Abstract

Large-scale phenotyping efforts have demonstrated that approximately 25-30% of mouse gene knockouts cause intrauterine lethality. Analysis of these mutants has largely focused on the embryo and not the placenta, despite the crucial role of this extraembryonic organ for developmental progression. Here we screened 103 embryonic lethal and sub-viable mouse knockout lines from the Deciphering the Mechanisms of Developmental Disorders program for placental phenotypes. We found that 68% of knockout lines that are lethal at or after mid-gestation exhibited placental dysmorphologies. Early lethality (embryonic days 9.5-14.5) is almost always associated with severe placental malformations. Placental defects correlate strongly with abnormal brain, heart and vascular development. Analysis of mutant trophoblast stem cells and conditional knockouts suggests that a considerable number of factors that cause embryonic lethality when ablated have primary gene function in trophoblast cells. Our data highlight the hugely under-appreciated importance of placental defects in contributing to abnormal embryo development and suggest key molecular nodes that govern placenta formation.

Comment in

PMID:
29539633
PMCID:
PMC5866719
DOI:
10.1038/nature26002
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center