Transitions in cell potency during early mouse development are driven by Notch
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Spain
- Sloan Kettering Institute, United States
Abstract
The Notch signalling pathway plays fundamental roles in diverse developmental processes in metazoans, where it is important in driving cell fate and directing differentiation of various cell types. However, we still have limited knowledge about the role of Notch in early preimplantation stages of mammalian development, or how it interacts with other signalling pathways active at these stages such as Hippo. By using genetic and pharmacological tools in vivo, together with image analysis of single embryos and pluripotent cell culture, we have found that Notch is active from the 4-cell stage. Transcriptomic analysis in single morula identified novel Notch targets, such as early naïve pluripotency markers or transcriptional repressors such as TLE4. Our results reveal a previously undescribed role for Notch in driving transitions during the gradual loss of potency that takes place in the early mouse embryo prior to the first lineage decisions.
Data availability
Sequencing data have been deposited in GEO under accession code GSE121979.
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Transitions in cell potency during early mouse development are driven by NotchNCBI Gene Expression Omnibus, GSE121979.
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The landscape of accessible chromatin in mammalian pre-implantation embryosNCBI Gene Expression Omnibus, GSE66390.
Article and author information
Author details
Anna-Katerina Hadjantonakis
Funding
Ministerio de Economía y Competitividad (BFU2017-84914-P)
- Sergio Menchero
- Isabel Rollan
- Antonio Lopez-Izquierdo
- Maria Jose Andreu
- Julio Sainz de Aja
- Javier Adan
- Teresa Rayon
- Miguel Manzanares
ProCNIC Foundation
- Sergio Menchero
- Isabel Rollan
- Antonio Lopez-Izquierdo
- Maria Jose Andreu
- Julio Sainz de Aja
- Javier Adan
- Rui Benedito
- Teresa Rayon
- Miguel Manzanares
National Institutes of Health (NIH-R01DK084391)
- Minjung Kang
- Anna-Katerina Hadjantonakis
Ministerio de Economía y Competitividad (BFU2015-72319-EXP)
- Sergio Menchero
- Isabel Rollan
- Maria Jose Andreu
- Miguel Manzanares
Ministerio de Economía y Competitividad (SEV-2015-0505)
- Sergio Menchero
- Isabel Rollan
- Antonio Lopez-Izquierdo
- Maria Jose Andreu
- Julio Sainz de Aja
- Javier Adan
- Rui Benedito
- Teresa Rayon
- Miguel Manzanares
Ministerio de Economía y Competitividad (SVP-2013-067930)
- Sergio Menchero
National Institutes of Health (NIH-R01HD094868)
- Minjung Kang
- Anna-Katerina Hadjantonakis
National Institutes of Health (NIH-P30CA008748)
- Minjung Kang
- Anna-Katerina Hadjantonakis
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with national and European Legislation. Procedures were approved by the CNIC Animal Welfare Ethics Committee and by the Area of Animal Protection of the Regional Government of Madrid (ref. PROEX 196/14).
Copyright
© 2019, Menchero et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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