“…Cadm4 mediates internodal axoglial adhesion by binding to axonal Cadm2 and Cadm3 in both the peripheral (Maurel et al, 2007;Spiegel et al, 2007) and the central (Pellissier et al, 2007;Sharma et al, 2015; Figure S4A) nervous systems. However, in line with the presence of multiple members of this family in both neurons and myelinating glia and their combinatorial heterophilic binding properties, as well as their redundant function in other systems (Fowler et al, 2017), genetic deletion of individual Cadm genes in mice resulted in only marginal myelination phenotypes (Golan et al, 2013;Park et al, 2008;Zhu et al, 2013). By using a different experimental approach that relies on the expression of the extracellular domain of Cadm4 in OLs, we reveal a critical role for cell adhesion in myelin targeting, membrane wrapping, and lateral extension of the myelin sheath.…”