Sfrp3 modulates stromal–epithelial crosstalk during mammary gland development by regulating Wnt levels

Ilenia Bernascone, Tamara González, Maria D. Barea, Claudia Carabaña, Mariam Hachimi, Minerva Bosch-Fortea, Silvia Santamaria, Raquel Martin, Julia Tarnick, Jose A. Garcia-Sanz and Fernando Martín-Belmonte ()
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Ilenia Bernascone: Centro de Biologia Molecular Severo Ochoa (CSIC-UAM)
Tamara González: Centro de Biologia Molecular Severo Ochoa (CSIC-UAM)
Maria D. Barea: Centro de Biologia Molecular Severo Ochoa (CSIC-UAM)
Claudia Carabaña: Centro de Biologia Molecular Severo Ochoa (CSIC-UAM)
Mariam Hachimi: Centro de Biologia Molecular Severo Ochoa (CSIC-UAM)
Minerva Bosch-Fortea: Centro de Biologia Molecular Severo Ochoa (CSIC-UAM)
Silvia Santamaria: Centro de Investigaciones Biologicas (CSIC)
Raquel Martin: Centro de Biologia Molecular Severo Ochoa (CSIC-UAM)
Julia Tarnick: University of Edinburgh
Jose A. Garcia-Sanz: Centro de Investigaciones Biologicas (CSIC)
Fernando Martín-Belmonte: Centro de Biologia Molecular Severo Ochoa (CSIC-UAM)

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: Abstract Mammary stroma is essential for epithelial morphogenesis and development. Indeed, postnatal mammary gland (MG) development is controlled locally by the repetitive and bi-directional cross-talk between the epithelial and the stromal compartment. However, the signalling pathways involved in stromal–epithelial communication are not entirely understood. Here, we identify Sfrp3 as a mediator of the stromal–epithelial communication that is required for normal mouse MG development. Using Drosophila wing imaginal disc, we demonstrate that Sfrp3 functions as an extracellular transporter of Wnts that facilitates their diffusion, and thus, their levels in the boundaries of different compartments. Indeed, loss of Sfrp3 in mice leads to an increase of ductal invasion and branching mirroring an early pregnancy state. Finally, we observe that loss of Sfrp3 predisposes for invasive breast cancer. Altogether, our study shows that Sfrp3 controls MG morphogenesis by modulating the stromal-epithelial cross-talk during pubertal development.

Date: 2019
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DOI: 10.1038/s41467-019-10509-1

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