On growth and form of the mouse mammary gland
- University of Helsinki, Finland
- INSERM and Sorbonne Universities, UPMC, France
Abstract
The mammary gland is a unique organ that undergoes dynamic alterations throughout a female's reproductive life, making it an ideal model for developmental, stem cell and cancer biology research. Mammary gland development begins in utero and proceeds via a quiescent bud stage before the initial outgrowth and subsequent branching morphogenesis. How mammary epithelial cells transit from quiescence to an actively proliferating and branching tissue during embryogenesis and, importantly, how the branch pattern is determined remain largely unknown. Here we provide evidence indicating that epithelial cell proliferation and onset of branching are independent processes, yet partially coordinated by the Eda signaling pathway. Through heterotypic and heterochronic epithelial-mesenchymal recombination experiments between mouse mammary and salivary gland tissues and ex vivo live imaging, we demonstrate that unlike previously concluded, the mode of branching is an intrinsic property of the mammary epithelium whereas the pace of growth and the density of ductal tree are determined by the mesenchyme. Transcriptomic profiling and ex vivo and in vivo functional studies in mice disclose that mesenchymal Wnt/ß-catenin signaling, and in particular IGF-1 downstream of it critically regulate mammary gland growth. These results underscore the general need to carefully deconstruct the different developmental processes producing branched organs.
Data availability
Sequencing data have been deposited in GEO under accession code GSE225821.
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On growth and form of the mouse mammary glandNCBI Gene Expression Omnibus, GSE225821.
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Fibroblast relays Wnt signals from endothelial niche to mammary epitheliumThe National Omics Data Encyclopedia, China National Center for Bioinformation, OEP001019.
Article and author information
Author details
Mona M Christensen
Martin Holzenberger
Funding
Research Council of Finland (318287)
- Marja L Mikkola
Sigrid Juséliuksen Säätiö
- Marja L Mikkola
Helsinki Institute of Life Science, Helsingin Yliopisto
- Marja L Mikkola
Helsingin Yliopiston Tiedesäätiö
- Ewelina Trela
Helsingin Yliopiston Tiedesäätiö
- Mona M Christensen
Suomen Kulttuurirahasto
- Jyoti Prabha Satta
Ella ja Georg Ehrnroothin Säätiö
- Jyoti Prabha Satta
Oskar Öflunds Stiftelse
- Qiang Lan
Suomen Kulttuurirahasto
- Beata Kaczyńska
Research Council of Finland (272280)
- Marja L Mikkola
Research Council of Finland (307421)
- Marja L Mikkola
Cancer Society of Finland
- Marja L Mikkola
Jane ja Aatos Erkon Säätiö
- Marja L Mikkola
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 mouse experiments were approved by the Laboratory Animal Center at the University of Helsinki and the National Animal Experiment Board of Finland with the licenses number KEK19-019, KEK22-014 and ESAVI/2363/04.10.07/2017. Mice were euthanized with CO2 followed by cervical dislocation.
Copyright
© 2024, Lan 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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On growth and form of the mouse mammary gland
eLife 13:e93326.
https://doi.org/10.7554/eLife.93326
