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Neuronal growth cones are highly motile structures that tip developing neurites and explore their surroundings before axo-dendritic contact and synaptogenesis. However, the membrane proteins organizing these processes remain insufficiently understood. Here we identify that the synaptic cell adhesion molecule 1 (SynCAM 1), an immunoglobulin superfamily member, is already expressed in developing neurons and localizes to their growth cones. Upon interaction of growth cones with target neurites, SynCAM 1 rapidly assembles at these contacts to form stable adhesive clusters. Synaptic markers can also be detected at these sites. Addressing the functions of SynCAM 1 in growth cones preceding contact, we determine that it is required and sufficient to restrict the number of active filopodia. Further, SynCAM 1 negatively regulates the morphological complexity of migrating growth cones. Focal adhesion kinase, a binding partner of SynCAM 1, is implicated in its morphogenetic activities. These results reveal that SynCAM 1 acts in developing neurons to shape migrating growth cones and contributes to the adhesive differentiation of their axo-dendritic contacts.

SynCAM 1 participates in axo-dendritic contact assembly and shapes neuronal growth cones