Mechanisms of Dendrite‐Specific Pruning in Drosophila Sensory Neurons


During animal development, pruning of unwanted or exuberant neurites is essential for the precise wiring of the nervous system. Holometabolous insects, such as the fruit fly Drosophila, undergo complete metamorphosis to replace their larval nervous systems with distinct adult ones. Many neurons in the central and peripheral nervous systems selectively prune away their larval dendrites and/or axons and regenerate their adult‐specific processes. Dendritic arborisation sensory neurons, ddaCs, specifically remove their larval dendrites in response to the steroid moulting hormone ecdysone and however keep their axons intact. Owing to their peripheral location, effectiveness of RNAi knockdown and convenience of single‐cell clonal analysis, ddaC neurons have emerged as an attractive system to dissect the pruning process for a decade. Some important genes and pathways, acting downstream of ecdysone signalling, have been discovered to enrich our understanding of neuronal pruning.

Key Concepts

  • Pruning is a mechanism for the refinement and maturation of the nervous system in various organisms including nematode, fruit fly and mammals.
  • ddaC sensory neurons undergo large‐scale dendrite‐specific pruning during early metamorphosis.
  • Ecdysone signalling is the master regulator of dendrite pruning in ddaC neurons.
  • A genetic pathway composed of Sox14 and Mical governs dendrite pruning in ddaC neurons.
  • Epigenetic factors regulate Sox14 expression and dendrite pruning in ddaC neurons.
  • Ubiquitin‐proteasome system (UPS) regulates different types of neurite pruning.
  • Endolysosomal degradation pathway downregulates the cell‐surface molecule Neuroglian (Nrg) to promote dendrite pruning.
  • Phagocytosis regulates fragmentation and clearance of severed dendrites.
  • Caspase is locally activated in the dendrites of ddaC neurons during pruning.
  • Calcium signalling is activated in the dendritic compartments to regulate dendrite pruning.

Keywords: neuron; dendrite; pruning; Drosophila; ecdysone signalling

Figure 1. Dendrite pruning of ddaC neurons involves at least three steps: severing, fragmentation and debris clearance. (A and A′) A ddaC neuron elaborates a complex dendrite arbour at the white pre‐pupal (WP) stage. The soma, proximal dendrites and axon are wrapped by peripheral glial cells (shown in red). (B and B′) The proximal dendritic regions form blebs, become thinner and are detached from the soma, a process known as severing. (C and C′) Severed dendrites undergo rapid fragmentation by approximately 12 h APF. The dendritic debris is engulfed and degraded by epidermal cells (shown in blue) and phagocytic hemocytes (shown in brown). (D and D′) By 16 h APF, the entire dendritic arbour is cleared up, leaving the soma and the intact axon. Scale bar, 50 µm.
Figure 2. The endolysosomal degradation pathway downregulates the cell adhesion molecule Neuroglian to facilitate dendrite severing in ddaC neurons. (A) the endolysosomal pathway governs dendrite pruning via downregulation of the cell adhesion molecule Nrg. (B) In wild type, Nrg is actively endocytosed from the plasma membrane and downregulated via lysosome‐mediated degradation before the onset of dendrite pruning. In Rab5 or ESCRT mutants, Nrg is dramatically accumulated on enlarged endosomes, probably leading to clog up of Nrg on the membrane and inhibition of dendrite pruning. Consistently, overexpression of Nrg resembles Rab5 or ESCRT mutants. Conversely, loss of nrg function causes destabilisation of dendrites and leads to precocious pruning.
Figure 3. Targets and co‐activators of EcR/Usp are critical for dendrite pruning in ddaC neurons. A genetic pathway composed of the transcription factor Sox14 and the cytoskeletal regulator Mical acts downstream of EcR/Usp nuclear receptors and plays an important role in governing dendrite pruning in ddaC neurons. Epigenetic regulators CBP and Brm facilitate the expression of Sox14. Caspase activation is likely regulated by Sox14. Hdc is a downstream target of EcR/Usp and play essential role in pruning. Sox14 enhances the expression of Cullin1 and other UPS components that downregulates the InR/PI3K/TOR pathway. The InR/PI3K/TOR pathway negatively regulates dendrite pruning in ddaC neurons.


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Further Reading

Boulanger A and Dura JM (2014) Nuclear receptors and Drosophila neuronal remodeling. Biochimica et Biophysica Acta 1849 (2): 187–195.

Neukomm LJ and Freeman MR (2014) Diverse cellular and molecular modes of axon degeneration. Trends in Cell Biology 24: 515–523.

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Zhang, Heng, and Yu, Fengwei(Apr 2015) Mechanisms of Dendrite‐Specific Pruning in Drosophila Sensory Neurons. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0025982]