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

Jessica Douthit,Carolyn A Morrison,Ariel Hairston,Jessica E Treisman,Isabel Holguera,Gina Lee

doi:10.7554/elife.65895

Abstract

As neural circuits form, growing processes select the correct synaptic partners through interactions between cell surface proteins. The presence of such proteins on two neuronal processes may lead to either adhesion or repulsion; however, the consequences of mismatched expression have rarely been explored. Here, we show that the Drosophila CUB-LDL protein Lost and found (Loaf) is required in the UV-sensitive R7 photoreceptor for normal axon targeting only when Loaf is also present in its synaptic partners. Although targeting occurs normally in loaf mutant animals, removing loaf from photoreceptors or expressing it in their postsynaptic neurons Tm5a/b or Dm9 in a loaf mutant causes mistargeting of R7 axons. Loaf localizes primarily to intracellular vesicles including endosomes. We propose that Loaf regulates the trafficking or function of one or more cell surface proteins, and an excess of these proteins on the synaptic partners of R7 prevents the formation of stable connections.

Highlights

During nervous system development, growing axons must navigate through a complex environment and select the correct synaptic partners from numerous potential choices.Recognition of cell surface molecules plays an important role in axon guidance and targeting and the establishment of specific synaptic connections (Yogev and Shen 2014)
(Figure 7- figure supplement 1C, D), indicating that Lar can compensate for the lack of loaf and is unlikely to be its primary effector. Consistent with this conclusion, we found that loaf was not required for HA-tagged Lar to be transported into photoreceptor axons
Expressing loaf RNAi in photoreceptors resulted in R7 mistargeting even in an Lrp4 null mutant background (Figure 7 - figure supplement 2J, K). These results show that Lost and found (Loaf) can affect the function of cell surface proteins, and suggest that it could act by regulating Lrp4 and/or other cell surface molecules that act as a readout of its levels to control the interactions between R7 and its postsynaptic partners

Summary

Introduction

During nervous system development, growing axons must navigate through a complex environment and select the correct synaptic partners from numerous potential choices. Recognition of cell surface molecules plays an important role in axon guidance and targeting and the establishment of specific synaptic connections (Yogev and Shen 2014). Interactions between cell surface molecules can lead to either adhesion or repulsion, and their relative levels on different cells are important for appropriate connections to form. As defects in synaptic adhesion molecules can lead to autism and other neurodevelopmental disorders (Van Battum et al 2015; Gilbert and Man 2017), identifying mechanisms that regulate synaptic partner choice is likely to enhance our understanding of such human diseases

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