For muscle stem cells (MuSCs), adhesion to the niche provides stable anchorage and proximity to signalling cues essential for quiescence. Previous studies have shown that combined loss of the two major cadherins, N and M, does not hinder normal niche localisation of MuSCs; however, N-cadherin is indispensable for maintaining MuSC quiescence. This raises an important question as to how MuSCs stably adhere to their niche. Here, Robert Krauss and colleagues show that, in mice, catenins are crucial for niche anchorage and preservation of quiescent MuSCs. First, the authors conditionally depleted two pairs of redundant catenins from MuSCs: αE- and αT-catenins (α-cdKO), and β- and γ-catenins (βγ-cdKO). They find that α-cdKO and βγ-cdKO mice show a steady decline in MuSCs over a 4-week period. In the absence of α-catenins, MuSCs exit the niche, undergo asynchronous activation and are eventually depleted through precocious differentiation. These phenotypes are more severe than those observed in MuSCs lacking the two abundant cadherins, suggesting that additional weakly expressed cadherins are likely involved in niche anchorage. Overall, this work reveals that separable functions of cadherin/catenin-based adhesions are crucial for niche localisation and maintenance of quiescence.
