Molecular Diversity of Dscam and Self-Recognition

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Cell recognition requires interactions through molecules located on cell surface. The insect homolog of Down syndrome cell adhesion molecule (Dscam) manifests huge molecular diversity in its extracellular domain. High-affinity Dscam-Dscam interactions only occur between isoforms that carry identical extracellular domains. Homophilic Dscam signaling can, thus, vary in strength depending on the compositions of Dscams present on the opposing cell surfaces. Dscam abundantly exists in the developing nervous system and governs arborization and proper elaboration of neurites. Notably, individual neurons may stochastically and dynamically express a small subset of Dscam isoforms such that any given neurite can be endowed with a unique repertoire of Dscams. This allows individual neurites to recognize their sister branches. Self-recognition leads to self-repulsion, ensuring divergent migration of sister processes. By contrast, weak homophilic Dscam interactions may promote fasciculation of neurites that express analogous, but not identical, Dscams. Differential Dscam binding may provide graded cell recognition that in turn governs complex neuronal morphogenesis.