Control of Synaptic Specificity by Establishing a Relative Preference for Synaptic Partners

• Published in: Neuron (Cambridge, Mass.) Vol. 103; no. 5; pp. 865 - 877.e7
• Main Authors: Xu, Chundi, Theisen, Emma, Maloney, Ryan, Peng, Jing, Santiago, Ivan, Yapp, Clarence, Werkhoven, Zachary, Rumbaut, Elijah, Shum, Bryan, Tarnogorska, Dorota, Borycz, Jolanta, Tan, Liming, Courgeon, Maximilien, Griffin, Tessa, Levin, Raina, Meinertzhagen, Ian A., de Bivort, Benjamin, Drugowitsch, Jan, Pecot, Matthew Y.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.09.2019; Elsevier Limited
• Subjects: Animals; Animals, Genetically Modified; Axon guidance; cell recognition molecules; Cell surface; Dpr and DIP proteins; Drosophila melanogaster; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Drosophila visual system; Gene expression; Immunoglobulins - genetics; Immunoglobulins - metabolism; Insects; Mate selection; Membrane Proteins - genetics; Membrane Proteins - metabolism; Nervous system; Neural networks; Neurons; Neurons - cytology; Neurons - metabolism; Optic Lobe, Nonmammalian - cytology; Optic Lobe, Nonmammalian - metabolism; Protein Interaction Maps; Proteins; synapse formation; Synapses - metabolism; synaptic specificity; Synaptogenesis; Visual pathways; Visual system; cell recognition molecules; Dpr and DIP proteins; synaptic specificity; Drosophila visual system; synapse formation
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2019.06.006

The ability of neurons to identify correct synaptic partners is fundamental to the proper assembly and function of neural circuits. Relative to other steps in circuit formation such as axon guidance, our knowledge of how synaptic partner selection is regulated is severely limited. Drosophila Dpr and DIP immunoglobulin superfamily (IgSF) cell-surface proteins bind heterophilically and are expressed in a complementary manner between synaptic partners in the visual system. Here, we show that in the lamina, DIP mis-expression is sufficient to promote synapse formation with Dpr-expressing neurons and that disrupting DIP function results in ectopic synapse formation. These findings indicate that DIP proteins promote synapses to form between specific cell types and that in their absence, neurons synapse with alternative partners. We propose that neurons have the capacity to synapse with a broad range of cell types and that synaptic specificity is achieved by establishing a preference for specific partners. •DIP-β is necessary for proper synaptic connectivity in the Drosophila visual system•DIPs-β and γ are sufficient to promote synapse formation in vivo•DIP IgSF proteins are necessary for proper visual function in Drosophila Xu et al. show that in the Drosophila visual system, DIP IgSF proteins are not necessary for synaptogenesis but regulate synaptic specificity by promoting synapses to form between specific cell types.