Epithelial tissue homeostasis relies on the elimination of superfluous cells while simultaneously maintaining an effective barrier. The ErbB receptor family (ErbB1, ErbB2, ErbB3 and ErbB4) initiates multiple key signal transduction pathways involved in epithelial homeostasis. Although the ligands and downstream pathways activated by each of the four receptors are well characterised, their individual contributions to complex epithelial cell behaviours, such as contact inhibition of proliferation, extrusion and collective cell migration, have not been clearly differentiated. In this Short Report (Matsuda et al., 2023), Kenta Terai and colleagues generate a series of Madin–Darby canine kidney (MDCK) cell lines carrying single or multiple knockouts of the four ErbB genes to map out functions of each receptor. They show that ErbB1 is primarily responsible for propagation of extracellular signal-regulated kinase (ERK) waves that drive collective migration of MDCK cells. Next, ErbB1, ErbB2 and ErbB3 cooperatively help regulate MDCK cell turnover, but through differing mechanisms: ErbB1 and ErbB2–ErbB3 heterodimers promote cell proliferation, whereas ErbB2 alone can specifically promote cell survival by antagonising compaction-induced apoptotic signalling and extrusion, which might aid epithelial tissues in maintaining sufficient cell density. This catalogue of ErbB-knockout MDCK cells represents a valuable resource to further dissect the cellular mechanisms that keep epithelial tissues in shape.
