| First Author | Neumann NM | Year | 2023 |
| Journal | J Cell Sci | Volume | 136 |
| Issue | 1 | PubMed ID | 36602106 |
| Mgi Jnum | J:367508 | Mgi Id | MGI:8209746 |
| Doi | 10.1242/jcs.259275 | Citation | Neumann NM, et al. (2023) Collective cell migration is spatiotemporally regulated during mammary epithelial bifurcation. J Cell Sci 136(1) |
| abstractText | Branched epithelial networks are generated through an iterative process of elongation and bifurcation. We sought to understand bifurcation of the mammary epithelium. To visualize this process, we utilized three-dimensional (3D) organotypic culture and time-lapse confocal microscopy. We tracked cell migration during bifurcation and observed local reductions in cell speed at the nascent bifurcation cleft. This effect was proximity dependent, as individual cells approaching the cleft reduced speed, whereas cells exiting the cleft increased speed. As the cells slow down, they orient both migration and protrusions towards the nascent cleft, while cells in the adjacent branches orient towards the elongating tips. We next tested the hypothesis that TGF-beta signaling controls mammary branching by regulating cell migration. We first validated that addition of TGF-beta1 (TGFB1) protein increased cleft number, whereas inhibition of TGF-beta signaling reduced cleft number. Then, consistent with our hypothesis, we observed that pharmacological inhibition of TGF-beta1 signaling acutely decreased epithelial migration speed. Our data suggest a model for mammary epithelial bifurcation in which TGF-beta signaling regulates cell migration to determine the local sites of bifurcation and the global pattern of the tubular network. |
