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

Abstract

4)These two authors contributed equally. AbstractThe formation of neural circuits requires growing processes to select the correct synaptic partners from a wide array of choices. This recognition depends on interactions between cell surface proteins, but quantitative comparisons of the levels of such proteins have been less considered as a source of synaptic specificity. Here we show that the relative levels of the Drosophila CUB-LDL protein Lost and found (Loaf) in the UV-sensitive R7 photoreceptor and its synaptic partners are important for normal R7 axon targeting. Although targeting occurs normally in loaf mutant animals, removing loaf from photoreceptors or restoring it to the synaptic partner neurons Tm5a/b or Dm9 in a loaf mutant causes R7 axons to terminate prematurely. Loaf localizes primarily to intracellular vesicles including endosomes. We suggest that Loaf regulates the trafficking or function of a transmembrane protein, and mismatched levels of this protein on R7 and its synaptic partners prevent stable synapse formation.

Brain connectivity inversely scales with developmental temperature in Drosophila

“…To quantitatively test how developmental processes and outcomes scale with developmental temperature, we devised a set of assays ranging from subcellular dynamics to behavior (Figure 1A). Subcellular dynamics and synapse formation of R7 photoreceptor neurons inversely scale with developmental temperature R7 photoreceptors in the Drosophila visual system are a wellstudied model for axon targeting and synapse formation in a columnar and layered brain region in vivo (Figure S1A) (Douthit et al, 2021;Hadjieconomou et al, 2011;Kolodkin and Hiesinger, 2017;Trush et al, 2019). To measure the temperature dependency of subcellular dynamics, we first performed live imaging of developing R7 axon terminals during synapse formation, for which we have previously described the underlying quantitative dynamics (O ¨zel et al, 2015, 2019).…”

Conservation and Innovation: Versatile Roles for LRP4 in Nervous System Development

“…Here, LRP4 is required for proper targeting of photoreceptor axons and may undergo regulation by another LDL family member, lost and found . Perturbation of lrp4 results in defects in target selection, but whether LRP4 is also involved in other aspects of visual system development, including synapse formation and function, remains unknown [ 78 ]. As LRP4 is expressed widely throughout the Drosophila brain [ 22 ] and the mammalian literature suggests diverse function, understanding how LRP4 promotes Drosophila synaptic development function may provide further insights into its versatile roles.…”