The mammary duct epithelium is an example of a highly branched epithelial network and the formation of these branched structures requires elongation and bifurcation of epithelial cells. Transforming growth factor-β (TGF-β) signalling is known to regulate this process, but the driving forces behind subsequent bifurcation are not fully understood. In this study (Neumann et al., 2023), Andrew Ewald and colleagues use 3D mammary organoids to study the cellular dynamics of epithelial bifurcation and investigate the effects of TGF-β signalling. Here, the authors find that cells reduce their migration speed when approaching the forming bifurcation. These slowing cells orient themselves and their protrusions towards the nascent cleft. Meanwhile, cells located laterally from the site of bifurcation migrate more quickly and orient towards the elongating branch tips. These changes are regulated by TGF-β signalling, given that its pharmacological inhibition significantly decreases epithelial migration speed. This results in a hyperbranched morphology, consistent with existing literature showing that TGF-β acts as a negative regulator of mammary branching. Together, these data identify local cellular dynamics during epithelial bifurcation and deepen our knowledge of how TGF-β regulates branching morphogenesis in the mammary epithelium.
