New insights into lumen formation in the mammary gland

During organogenesis, lumen formation is essential for building a network of epithelial tubes. In the mammary gland, lumen formation occurs upon stimulation with lactogenic hormones, whereby epithelial cells undergo dramatic cellular rearrangements to form lobular structures comprised of single-layered cysts. These cysts are surrounded by a layer of myoepithelial cells, which produce basement membrane (BM). In a new study, Yuina Hirose and Yohei Hirai (Hirose and Hirai, 2021) use 3D aggregates of murine mammary epithelial EpH4 cells to study lumen formation upon treatment with the lactogenic hormone prolactin. They find that prolactin induces membrane translocation of the t-SNARE protein syntaxin4, which in turn induces rapid turnover of E-cadherin, thereby instructing dynamic cellular rearrangements and the formation of cystic structures. Importantly, the change in cellular behaviour is dependent on whether syntaxin4-expressing cells are cultured on BM signal-containing Matrigel, and this suggests that cells facing the BM-producing myoepithelial cells undergo cyst formation whereas cells situated away from the myoepithelial cells migrate outwards. Collectively, these findings support a model where epithelial morphogenesis in the mammary gland is regulated by the cooperation of syntaxin4 and BM.