Common and distinct transcriptional signatures of mammalian embryonic lethality

John E. Collins, Richard J. White, Nicole Staudt, Ian M. Sealy, Ian Packham, Neha Wali, Catherine Tudor, Cecilia Mazzeo, Angela Green, Emma Siragher, Edward Ryder, Jacqueline K. White, Irene Papatheodoru, Amy Tang, Anja Füllgrabe, Konstantinos Billis, Stefan H. Geyer, Wolfgang J. Weninger, Antonella Galli, Myriam Hemberger, Derek L. Stemple, Elizabeth Robertson, James C. Smith, Timothy Mohun, David J. Adams and Elisabeth M. Busch-Nentwich ()
Additional contact information
John E. Collins: Wellcome Sanger Institute, Wellcome Genome Campus
Richard J. White: Wellcome Sanger Institute, Wellcome Genome Campus
Nicole Staudt: Wellcome Sanger Institute, Wellcome Genome Campus
Ian M. Sealy: Wellcome Sanger Institute, Wellcome Genome Campus
Ian Packham: Wellcome Sanger Institute, Wellcome Genome Campus
Neha Wali: Wellcome Sanger Institute, Wellcome Genome Campus
Catherine Tudor: Wellcome Sanger Institute, Wellcome Genome Campus
Cecilia Mazzeo: Wellcome Sanger Institute, Wellcome Genome Campus
Angela Green: Wellcome Sanger Institute, Wellcome Genome Campus
Emma Siragher: Wellcome Sanger Institute, Wellcome Genome Campus
Edward Ryder: Wellcome Sanger Institute, Wellcome Genome Campus
Jacqueline K. White: Wellcome Sanger Institute, Wellcome Genome Campus
Irene Papatheodoru: European Bioinformatics Institute, Wellcome Genome Campus
Amy Tang: European Bioinformatics Institute, Wellcome Genome Campus
Anja Füllgrabe: European Bioinformatics Institute, Wellcome Genome Campus
Konstantinos Billis: European Bioinformatics Institute, Wellcome Genome Campus
Stefan H. Geyer: Medical University of Vienna
Wolfgang J. Weninger: Medical University of Vienna
Antonella Galli: Wellcome Sanger Institute, Wellcome Genome Campus
Myriam Hemberger: The Babraham Institute, Babraham Research Campus
Derek L. Stemple: Wellcome Sanger Institute, Wellcome Genome Campus
Elizabeth Robertson: University of Oxford
James C. Smith: The Francis Crick Institute
Timothy Mohun: The Francis Crick Institute
David J. Adams: Wellcome Sanger Institute, Wellcome Genome Campus
Elisabeth M. Busch-Nentwich: Wellcome Sanger Institute, Wellcome Genome Campus

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract The Deciphering the Mechanisms of Developmental Disorders programme has analysed the morphological and molecular phenotypes of embryonic and perinatal lethal mouse mutant lines in order to investigate the causes of embryonic lethality. Here we show that individual whole-embryo RNA-seq of 73 mouse mutant lines (>1000 transcriptomes) identifies transcriptional events underlying embryonic lethality and associates previously uncharacterised genes with specific pathways and tissues. For example, our data suggest that Hmgxb3 is involved in DNA-damage repair and cell-cycle regulation. Further, we separate embryonic delay signatures from mutant line-specific transcriptional changes by developing a baseline mRNA expression catalogue of wild-type mice during early embryogenesis (4–36 somites). Analysis of transcription outside coding sequence identifies deregulation of repetitive elements in Morc2a mutants and a gene involved in gene-specific splicing. Collectively, this work provides a large scale resource to further our understanding of early embryonic developmental disorders.

Date: 2019
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DOI: 10.1038/s41467-019-10642-x

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