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Transitions in cell potency during early mouse development are driven by Notch.

Sergio Menchero1, Isabel Rollan1, Antonio Lopez-Izquierdo1

  • 1Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.

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|April 9, 2019
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Summary

Notch signalling is active early in mouse development, influencing cell potency transitions before lineage decisions. This pathway regulates pluripotency markers and transcriptional repressors during preimplantation stages.

Keywords:
Cdx2chromosomesdevelopmental biologygene expressionmorulamousenotchpreimplantation developmenttrophectoderm

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Area of Science:

  • Developmental Biology
  • Cell Signalling
  • Mammalian Embryogenesis

Background:

  • The Notch signalling pathway is crucial for cell fate determination and differentiation in metazoans.
  • Its role in early mammalian preimplantation development and interaction with pathways like Hippo remains largely unknown.

Purpose of the Study:

  • To investigate the activity and function of Notch signalling during early mouse preimplantation development.
  • To identify Notch targets and understand its interplay with pluripotency and lineage decisions.

Main Methods:

  • In vivo genetic and pharmacological manipulation of Notch signalling in mouse embryos.
  • Single embryo image analysis and pluripotent cell culture.
  • Single-cell transcriptomic analysis of morula stage embryos.

Main Results:

  • Notch signalling is active from the 4-cell stage in mouse embryos.
  • Novel Notch targets include early naïve pluripotency markers and transcriptional repressors like TLE4.
  • Notch signalling drives gradual loss of potency prior to first lineage decisions.

Conclusions:

  • Notch signalling plays a significant, previously unrecognized role in early mammalian preimplantation development.
  • It modulates pluripotency and influences the transition towards lineage commitment.
  • Understanding Notch's role provides insights into fundamental developmental processes.