1. Developmental Biology
  2. Stem Cells and Regenerative Medicine

Imprinted Dlk1 dosage as a size determinant of the mammalian pituitary gland

  1. Valeria Scagliotti
  2. Maria Lillina Vignola
  3. Thea L Willis
  4. Mark Howard
  5. Eugenia Marinelli
  6. Carles Gaston-Massuet
  7. Cynthia Lilian Andoniadou
  8. Marika Charalambous  Is a corresponding author
  1. King's College London, United Kingdom
  2. Queen Mary University of London, United Kingdom
https://doi.org/10.7554/eLife.84092
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  1. Valeria Scagliotti
  2. Maria Lillina Vignola
  3. Thea L Willis
  4. Mark Howard
  5. Eugenia Marinelli
  6. Carles Gaston-Massuet
  7. Cynthia Lilian Andoniadou
  8. Marika Charalambous
(2023)
Imprinted Dlk1 dosage as a size determinant of the mammalian pituitary gland
eLife 12:e84092.
https://doi.org/10.7554/eLife.84092
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Abstract

Co-regulated genes of the Imprinted Gene Network are involved in the control of growth and body size, and imprinted gene dysfunction underlies human paediatric disorders involving the endocrine system. Imprinted genes are highly expressed in the pituitary gland, among them, Dlk1, a paternally expressed gene whose membrane-bound and secreted protein products can regulate proliferation and differentiation of multiple stem cell populations. Dosage of circulating DLK1 has been previously implicated in the control of growth through unknown molecular mechanisms. Here we generate a series of mouse genetic models to modify levels of Dlk1 expression in the pituitary gland and demonstrate that the dosage of DLK1 modulates the process of stem cell commitment with lifelong impact on pituitary gland size. We establish that stem cells are a critical source of DLK1, where embryonic disruption alters proliferation in the anterior pituitary, leading to long-lasting consequences on growth hormone secretion later in life.

Data availability

Sequencing data have previously been deposited in GEO under accession codes GSE120410, GSE142074, GSE178454.Figure 1 - Source Data 1, Figure 4 - Source Data 1, Figure 5&6 - Source Data 1 contain the numerical data used to generate the figures.

The following previously published data sets were used

Article and author information

Author details

  1. Valeria Scagliotti

    Department of Medical and Molecular Genetics, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  2. Maria Lillina Vignola

    Department of Medical and Molecular Genetics, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7121-7715

  3. Thea L Willis

    Department of Medical and Molecular Genetics, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1794-7490

  4. Mark Howard

    Peter Gorer Department of Immunobiology, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  5. Eugenia Marinelli

    Department of Medical and Molecular Genetics, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  6. Carles Gaston-Massuet

    Centre for Endocrinology, Queen Mary University of London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  7. Cynthia Lilian Andoniadou

    Centre for Craniofacial and Regenerative Biology, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4311-5855

  8. Marika Charalambous

    Department of Medical and Molecular Genetics, King's College London, London, United Kingdom
    For correspondence
    marika.charalambous@kcl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1684-5783

Funding

Medical Research Council (MR/L002345/1)

  • Mark Howard
  • Marika Charalambous

Barts Charity (MGU0551)

  • Carles Gaston-Massuet

Medical Research Council (MR/R022836/1)

  • Valeria Scagliotti
  • Eugenia Marinelli
  • Marika Charalambous

Medical Research Council (MR/T012153/1)

  • Cynthia Lilian Andoniadou

Merck Healthcare KGaA (GGI 2020)

  • Valeria Scagliotti
  • Maria Lillina Vignola
  • Marika Charalambous

Society for Endocrinology (ECR Grant)

  • Mark Howard

Guy's and St Thomas' NHS Foundation Trust (BRC-NIHR PhD studentship)

  • Maria Lillina Vignola

King's College London (Cell Therapies and Regenerative Medicine" Four-Year Welcome Trust PhD Training Program")

  • Thea L Willis

Action Medical Research (GN2272)

  • Carles Gaston-Massuet

Barts Charity (GN 417/2238)

  • Carles Gaston-Massuet

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

Copyright

© 2023, Scagliotti 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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  1. Valeria Scagliotti
  2. Maria Lillina Vignola
  3. Thea L Willis
  4. Mark Howard
  5. Eugenia Marinelli
  6. Carles Gaston-Massuet
  7. Cynthia Lilian Andoniadou
  8. Marika Charalambous
(2023)
Imprinted Dlk1 dosage as a size determinant of the mammalian pituitary gland
eLife 12:e84092.
https://doi.org/10.7554/eLife.84092

Share this article

https://doi.org/10.7554/eLife.84092

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