Cell surface molecule, Klingon, mediates the refinement of synaptic specificity in the Drosophila visual system

Abstract

In the Drosophila brain, neurons form genetically specified synaptic connections with defined neuronal targets. It is proposed that each central nervous system neuron expresses specific cell surface proteins, which act as identification tags. Through an RNAi screen of cell surface molecules in the Drosophila visual system, we found that the cell adhesion molecule Klingon (Klg) plays an important role in repressing the ectopic formation of extended axons, preventing the formation of excessive synapses. Cell‐specific manipulation of klg showed that Klg is required in both photoreceptors and the glia, suggesting that the balanced homophilic interaction between photoreceptor axons and the glia is required for normal synapse formation. Previous studies suggested that Klg binds to cDIP and our genetic analyses indicate that cDIP is required in glia for ectopic synaptic repression. These data suggest that Klg play a critical role together with cDIP in refining synaptic specificity and preventing unnecessary connections in the brain.

R7 photoreceptor axon targeting depends on the relative levels of lost and found expression in R7 and its synaptic partners

“…The most parsimonious explanation for these phenotypes is that a mismatch in Loaf expression between R7 and its partners results in mistargeting. A similar phenomenon was observed for the homophilic cell adhesion molecule Klingon, which affects synapse formation when removed from either R7 or glial cells, but not when removed from both simultaneously ( Shimozono et al, 2019 ). Matching pre- and postsynaptic levels are also important for the Drosophila Teneurin proteins to promote synapse formation ( Hong et al, 2012 ; Mosca et al, 2012 ).…”

“…It is not known which, if any, of these cell types provide Ncad or RPTP ligands that stabilize filopodia from the R7 growth cone ( Yonekura et al, 2007 ; Hofmeyer and Treisman, 2009 ; Hakeda-Suzuki et al, 2017 ; Özel et al, 2019 ). Glia are also involved in establishing the pattern of R7 synaptogenesis, as they prevent excessive synapse formation through the adhesion protein Klingon (Klg) and its partner cDIP ( Shimozono et al, 2019 ).…”

R7 photoreceptor axon targeting depends on the relative levels oflost and foundexpression in R7 and its synaptic partners

“…The most parsimonious explanation for this is that a mismatch in the levels of Loaf between R7 and its partners results in mistargeting. A similar phenomenon was observed for Klingon, which affects synapse formation when removed from either R7 or glial cells, but not when removed from both simultaneously (Shimozono et al, 2019). Matching pre-and postsynaptic levels are also important for the Drosophila Teneurin proteins to promote synapse formation .…”

“…It is not known which, if any, of these cell types provide Ncad or RPTP ligands that stabilize filopodia from the R7 growth cone (Hofmeyer and Treisman, 2009, Yonekura et al, 2007, Hakeda-Suzuki et al, 2017, Ozel et al, 2019. Glia are also involved in establishing the pattern of R7 synaptogenesis, as they prevent excessive synapse formation through the adhesion protein Klingon (Klg) and its partner cDIP (Shimozono 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 ).…”