Imprinted Dlk1 dosage as a size determinant of the mammalian pituitary gland
- King's College London, United Kingdom
- Queen Mary University of London, United Kingdom
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.
Article and author information
Author details
Maria Lillina Vignola
Cynthia Lilian Andoniadou
Marika Charalambous
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.
Reviewing Editor
- T Rajendra Kumar, University of Colorado, United States
Version history
- Received: October 10, 2022
- Preprint posted: November 2, 2022 (view preprint)
- Accepted: August 16, 2023
- Accepted Manuscript published: August 17, 2023 (version 1)
- Version of Record published: August 30, 2023 (version 2)
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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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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