Calcium transients regulate epithelial integration of multiciliated cells during Xenopus skin development

Abstract Integration basally located progenitors into an existing epithelium is crucial for tissue morphogenesis during embryogenesis and tissue homeostasis of epithelial organs. In this study, using Xenopus as a model system, we explore the role of intracellular calcium in multiciliated cell (MCC) progenitors’ epithelial integration during mucociliary skin epithelium development. Our findings reveal that calcium transients precede MCC apical emergence and are essential for their successful insertion into the overlying skin epithelium. Furthermore, we demonstrate that phospholipase C (PLC) activity is required for the generation of calcium transients, which in turn regulate MCC epithelial integration via the calcium-binding protein calmodulin. Last, we demonstrate that the PLC/Ca²⁺/calmodulin axis is necessary for proper formation of the apical actin network, by influencing its stability. This study advances our understanding of the molecular mechanisms governing epithelial integration of basal progenitors and highlights the importance of calcium signalling in coordinating cytoskeletal dynamics during epithelial morphogenesis.