1. Developmental Biology

NOTCH activity differentially affects pituitary endocrine cell fate acquisition and maintenance

  1. Leonard Cheung
  2. Paul Le Tissier
  3. Sam GJ Goldsmith
  4. Mathias Treier
  5. Robin Lovell-Badge
  6. Karine Rizzoti  Is a corresponding author
  1. University of Michigan, United States
  2. University of Edinburgh, United Kingdom
  3. The Francis Crick Institute, United Kingdom
  4. Max Delbruck Center for Molecular Medicine, Germany
https://doi.org/10.7554/eLife.33318
Share this article
Cite this article
  1. Leonard Cheung
  2. Paul Le Tissier
  3. Sam GJ Goldsmith
  4. Mathias Treier
  5. Robin Lovell-Badge
  6. Karine Rizzoti
(2018)
NOTCH activity differentially affects pituitary endocrine cell fate acquisition and maintenance
eLife 7:e33318.
https://doi.org/10.7554/eLife.33318
  2. Download BibTeX
  3. Download .RIS

Abstract

The pituitary is an essential endocrine gland regulating multiple processes. Regeneration of endocrine cells is of therapeutic interest and recent studies are promising, but mechanisms of endocrine cell fate acquisition need to be better characterised. The NOTCH pathway is important during pituitary development. Here, we further characterise its role in the murine pituitary, revealing differential sensitivity within and between lineages. In progenitors, NOTCH activation blocks cell fate acquisition, with time-dependant modulation. In differentiating cells, response to activation is blunted in the POU1F1 lineage, with apparently normal cell fate specification, while POMC cells remain sensitive. Absence of apparent defects in Pou1f1-Cre; Rbpjfl/fl mice further suggests no direct role for NOTCH signalling in POU1F1 cell fate acquisition. In contrast, in the POMC lineage, NICD expression induces a regression towards a progenitor-like state, suggesting that the NOTCH pathway specifically blocks POMC cell differentiation. These results have implications for pituitary development, plasticity and regeneration.

Article and author information

Author details

  1. Leonard Cheung

    Department of Human Genetics, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0912-9594

  2. Paul Le Tissier

    Centre for Discovery Brain Science, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  3. Sam GJ Goldsmith

    Stem Cell Biology and Developmental Genetics, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  4. Mathias Treier

    Genetics of Metabolic and Reproductive Disorders, Max Delbruck Center for Molecular Medicine, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.

  5. Robin Lovell-Badge

    Stem Cell Biology and Developmental Genetics, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  6. Karine Rizzoti

    Stem Cell Biology and Developmental Genetics, The Francis Crick Institute, London, United Kingdom
    For correspondence
    Karine.Rizzoti@crick.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0711-5452

Funding

Medical Research Council (U117562207)

  • Paul Le Tissier

Cancer Research UK (FC001107)

  • Robin Lovell-Badge

Medical Research Council (U117512772)

  • Robin Lovell-Badge

Medical Research Council (FC001107)

  • Robin Lovell-Badge

Wellcome (FC001107)

  • Robin Lovell-Badge

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experiments carried out on mice were approved under the UK Animal (scientific procedures) Act (Project licence 80/2405 and 70/8560).

Copyright

© 2018, Cheung 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.

Metrics

  • 1,674
    views
  • 295
    downloads
  • 17
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Leonard Cheung
  2. Paul Le Tissier
  3. Sam GJ Goldsmith
  4. Mathias Treier
  5. Robin Lovell-Badge
  6. Karine Rizzoti
(2018)
NOTCH activity differentially affects pituitary endocrine cell fate acquisition and maintenance
eLife 7:e33318.
https://doi.org/10.7554/eLife.33318

Share this article

https://doi.org/10.7554/eLife.33318

Categories and tags

Research organism

Further reading

    1. Developmental Biology

    Emerging cooperativity between Oct4 and Sox2 governs the pluripotency network in early mouse embryos

    Yanlin Hou, Zhengwen Nie ... Hans R Scholer
    Research Article

    During the first lineage segregation, mammalian embryos generate the inner cell mass (ICM) and trophectoderm (TE). ICM gives rise to the epiblast (EPI) that forms all cell types of the body, an ability referred to as pluripotency. The molecular mechanisms that induce pluripotency in embryos remain incompletely elucidated. Using knockout (KO) mouse models in conjunction with low-input ATAC-seq and RNA-seq, we found that Oct4 and Sox2 gradually come into play in the early ICM, coinciding with the initiation of Sox2 expression. Oct4 and Sox2 activate the pluripotency-related genes through the putative OCT-SOX enhancers in the early ICM. Furthermore, we observed a substantial reorganization of chromatin landscape and transcriptome from the morula to the early ICM stages, which was partially driven by Oct4 and Sox2, highlighting their pivotal role in promoting the developmental trajectory toward the ICM. Our study provides new insights into the establishment of the pluripotency network in mouse preimplantation embryos.

    1. Developmental Biology

    Morphogenesis: Fluid transport comes to the fore

    Yufei Wu, Sean X Sun
    Insight

    Proteins that allow water to move in and out of cells help shape the development of new blood vessels.

    1. Developmental Biology
    2. Neuroscience

    Axon Guidance: Watching axons on the move

    Maria I Lazaro-Pena, Carlos A Diaz-Balzac
    Insight

    The ligand Netrin mediates axon guidance through a combination of haptotaxis over short distances and chemotaxis over longer distances.