Abstract

During development, certain Drosophila sensory neurons undergo dendrite pruning that selectively eliminates their dendrites but leaves the axons intact. How these neurons regulate pruning activity in the dendrites remains unknown. Here, we identify a coiled-coil protein Spindle-F (Spn-F) that is required for dendrite pruning in Drosophila sensory neurons. Spn-F acts downstream of IKK-related kinase Ik2 in the same pathway for dendrite pruning. Spn-F exhibits a punctate pattern in larval neurons, whereas these Spn-F puncta become redistributed in pupal neurons, a step that is essential for dendrite pruning. The redistribution of Spn-F from puncta in pupal neurons requires the phosphorylation of Spn-F by Ik2 kinase to decrease Spn-F self-association, and depends on the function of microtubule motor dynein complex. Spn-F is a key component to link Ik2 kinase to dynein motor complex, and the formation of Ik2/Spn-F/dynein complex is critical for Spn-F redistribution and for dendrite pruning. Our findings reveal a novel regulatory mechanism for dendrite pruning achieved by temporal activation of Ik2 kinase and dynein-mediated redistribution of Ik2/Spn-F complex in neurons.

Highlights

  • The precise assembly of neural circuits is crucial for the nervous system to function properly

  • Author Summary In Drosophila, the nervous systems undergo extensive neuronal remodeling during metamorphosis, as many larval neurons die and adult neurons are generated while some larval neurons survive and prune their branches

  • Results spn-F is required for dendrite pruning of Drosophila sensory neurons

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Summary

Introduction

The precise assembly of neural circuits is crucial for the nervous system to function properly. The developing nervous systems often start with a primitive prototype, characterized by exuberant branches and excessive connections. Further remodeling is required to refine the developing nervous systems to maturity. Neuronal pruning, one such remodeling mechanism, is a highly regulated self-destruct process that eliminates excessive neuronal branches in the absence of cell death. Pruning is widely observed in the nervous systems of both vertebrates and invertebrates [1,2], that ensures precise wiring during development, and allows for adjustment of neuronal connections in response to injury and disease. Various studies have shown that defects in developmental pruning affect the function of the nervous systems in C. elegans [3] and Drosophila [4]. Microtubule disruption is the earliest cellular event observed in all types of pruning [2,7,8], and the ubiquitin-proteasome system is required in all circumstances [7,8,9,10]

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