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

Abstract

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 misexpression 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.

Neurogenetic and genomic approaches reveal roles for Dpr/DIP cell adhesion molecules inDrosophilareproductive behavior

“…CC-BY 4.0 International license available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made The copyright holder for this preprint this version posted October 4, 2020. ; https://doi.org/10.1101/2020.10.02.323477 doi: bioRxiv preprint interactome partner pairs mediating these critical functions (CARRILLO et al 2015;TAN et al 2015;BARISH et al 2018;XU et al 2018;ASHLEY et al 2019;COURGEON AND DESPLAN 2019;MENON et al 2019;VENKATASUBRAMANIAN et al 2019;XU et al 2019). Our screen to identify morphological or synaptic changes in fru P1 ∩ DIP-α and DIP-δ neurons, using dpr/DIP RNAi or overexpression transgenes identified only one perturbation with an impact; reduction of DIP-ε by RNAi on the fru P1 ∩ DIP-α pattern, with both cell autonomous and non-autonomous roles.…”

“…Additionally, some Dprs interact dimerically with Dprs through either heterophilic or homophilic interactions, and some of the DIPs interact dimerically through homophilic interactions (OZKAN et al 2013;CARRILLO et al 2015;COSMANESCU et al 2018)(summarized in Supplemental Table 1). Functional analyses of the Dprs and DIPs have revealed roles in synaptic connectivity and specificity of neuronal targeting in the Drosophila neuromuscular junction, visual system and olfactory system (CARRILLO et al 2015;TAN et al 2015;BARISH et al 2018;XU et al 2018;ASHLEY et al 2019;COURGEON AND DESPLAN 2019;MENON et al 2019;VENKATASUBRAMANIAN et al 2019;XU et al 2019). Cell adhesion molecules have already been shown to be important for sculpting dimorphism in fru P1 neurons, with studies of the IgSF member encoded by roundabout (robo) shown to be a direct target of Fru M and responsible for dimorphic projections and morphology (MELLERT et al 2010;ITO et al 2016).…”

Interactions between Dpr11 and DIP-γ control selection of amacrine neurons in Drosophila color vision circuits

“…Dprs and DIPs regulate fasciculation and sorting of olfactory receptor neuron axons in the antennal lobe (Barish et al, 2018). In the lamina of the OL, DIPs prevent ectopic synapse formation (Xu et al, 2019).…”

The Drosophila Split Gal4 System for Neural Circuit Mapping

“…Although the availability of these techniques has somewhat mitigated the need for Split Gal4, the latter method has also found productive application in the study of numerous developmental processes. These include neuronal differentiation (Seroka and Doe, 2019 ), target matching and synaptogenesis (Couton et al, 2015 ; Courgeon and Desplan, 2019 ; Menon et al, 2019 ; Xu et al, 2019 ), and neuron-glia interactions (Coutinho-Budd et al, 2017 ; McLaughlin et al, 2019 ; Shimozono et al, 2019 ). Also, the characterization of postembryonic neuroblast lineages has profited from the application Split Gal4 methods (Lacin and Truman, 2016 ; Lacin et al, 2020 ; Figures 8A–C ).…”