Sfrp3 modulates stromal-epithelial crosstalk during mammary gland development by regulating Wnt levels
Sfrp3 modulates stromal-epithelial crosstalk during mammary gland development by regulating Wnt levels
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DOI：
10.1038/s41467-019-10509-1
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发表时间：
2019-06-06
影响因子：
16.6
通讯作者：
Martin-Belmonte, Fernando
中科院分区：
文献类型：
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作者：
Bernascone, Ilenia;Gonzalez, Tamara;Martin-Belmonte, Fernando
乳腺间质是上皮细胞形态发生和发育所必需的。事实上，出生后乳腺（MG）的发展是局部控制的上皮和间质室之间的重复和双向的串扰。然而，基质-上皮细胞通讯中涉及的信号通路还不完全清楚。在这里，我们确定Sfrp 3作为介导的基质上皮通信是正常小鼠MG发展所需的。使用果蝇翼成虫盘，我们证明了Sfrp 3作为Wnt的细胞外转运蛋白，促进它们的扩散，因此，它们在不同隔室的边界水平。事实上，小鼠中Sfrp 3的缺失导致导管侵入和分支的增加，反映了早期妊娠状态。最后，我们观察到Sfrp 3的缺失易患浸润性乳腺癌。总之，我们的研究表明，Sfrp 3控制MG形态发生，通过调节基质上皮细胞的串扰在青春期发育。
Mammary stroma is essential for epithelial morphogenesis and development. Indeed, postnatal mammary gland (MG) development is controlled locally by the repetitive and bidirectional 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.