The molecular basis of self-avoidance

• Published in: Annual review of neuroscience 2013-07, Vol.36 (1), p.547-568
• Main Authors: Zipursky, S Lawrence, Grueber, Wesley B
• Format: Article
• Language: English
• Subjects: Alternative splicing; Animals; Biological Evolution; Cadherins - genetics; Cadherins - metabolism; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Communication - physiology; Dendrites - physiology; Drosophila; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Gene expression; Immunoglobulins; Immunoglobulins - genetics; Immunoglobulins - physiology; Insects; Molecular biology; Neurons; Neurons - cytology; Neurons - physiology; Neurosciences
• ISSN: 0147-006X; 1545-4126
• DOI: 10.1146/annurev-neuro-062111-150414

Self-avoidance, the tendency of neurites of the same cell to selectively avoid each other, is a property of both vertebrate and invertebrate neurons. In Drosophila, self-avoidance is mediated by a large family of cell recognition molecules of the immunoglobulin superfamily encoded, via alternative splicing, by the Dscam1 locus. Dscam1 promotes self-avoidance in dendrites, axons, and prospective postsynaptic elements. Expression analysis suggests that each neuron expresses a unique combination of isoforms. Identical isoforms on sister neurites exhibit isoform-specific homophilic recognition and elicit repulsion between processes, thereby promoting self-avoidance. Although any isoform can promote self-avoidance, thousands are necessary to ensure that neurites readily discriminate between self and nonself. Recent studies indicate that a large family of cadherins in the mouse, i.e., the clustered protocadherins, functions in an analogous fashion to promote self-avoidance. These studies argue for the evolution of a common molecular strategy for self-avoidance.