Epidermal Cells Are the Primary Phagocytes in the Fragmentation and Clearance of Degenerating Dendrites in Drosophila

Han, Chun; Song, Yuanquan; Xiao, Hui; Wang, Denan; Franc, Nathalie C.; Jan, Yuh Nung

doi:10.1016/j.neuron.2013.11.021

Cited by 136 publications

(187 citation statements)

References 70 publications

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“…However, the dendrite pruning defects caused by those UPS mutants are much stronger than the phenotypes caused by caspase inactivation, which mostly causes a delay in the phagocytic uptake of severed dendrites by the epidermis (6,34). Although we cannot exclude that ubcD1 and VCP contribute to caspase activation during pruning, the new mechanism proposed herecontrol of RNA-binding proteins and MICAL expression-likely makes a much stronger contribution to the drastic pruning phenotypes of UPS mutants.…”

Section: Resultsmentioning

confidence: 81%

Drosophila Valosin-Containing Protein is required for dendrite pruning through a regulatory role in mRNA metabolism

Rumpf

Bagley

Thompson-Peer

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The dendritic arbors of the larval Drosophila peripheral class IV dendritic arborization neurons degenerate during metamorphosis in an ecdysone-dependent manner. This process-also known as dendrite pruning-depends on the ubiquitin-proteasome system (UPS), but the specific processes regulated by the UPS during pruning have been largely elusive. Here, we show that mutation or inhibition of Valosin-Containing Protein (VCP), a ubiquitin-dependent ATPase whose human homolog is linked to neurodegenerative disease, leads to specific defects in mRNA metabolism and that this role of VCP is linked to dendrite pruning. Specifically, we find that VCP inhibition causes an altered splicing pattern of the large pruning gene molecule interacting with CasL and mislocalization of the Drosophila homolog of the human RNA-binding protein TAR-DNA-binding protein of 43 kilo-Dalton (TDP-43). Our data suggest that VCP inactivation might lead to specific gain-of-function of TDP-43 and other RNA-binding proteins. A similar combination of defects is also seen in a mutant in the ubiquitin-conjugating enzyme ubcD1 and a mutant in the 19S regulatory particle of the proteasome, but not in a 20S proteasome mutant. Thus, our results highlight a proteolysis-independent function of the UPS during class IV dendritic arborization neuron dendrite pruning and link the UPS to the control of mRNA metabolism.

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Section: Resultsmentioning

confidence: 81%

Drosophila Valosin-Containing Protein is required for dendrite pruning through a regulatory role in mRNA metabolism

Rumpf

Bagley

Thompson-Peer

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…[28][29][30][31] Previously, we found that Draper was required earlier in oogenesis for the clearance of nurse cells undergoing apoptosis in response to starvation. 32 Interestingly, we also found that overexpression of Draper in follicle cells was sufficient to kill the underlying germline cells.…”

Section: Role Of Engulfment Genes In Nurse Cell Deathmentioning

confidence: 99%

Control of non-apoptotic nurse cell death by engulfment genes in Drosophila

Timmons

Mondragon

Meehan

et al. 2016

Fly

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Programmed cell death occurs as a normal part of oocyte development in Drosophila. For each egg that is formed, 15 germline-derived nurse cells transfer their cytoplasmic contents into the oocyte and die. Disruption of apoptosis or autophagy only partially inhibits the death of the nurse cells, indicating that other mechanisms significantly contribute to nurse cell death. Recently, we demonstrated that the surrounding stretch follicle cells non-autonomously promote nurse cell death during late oogenesis and that phagocytosis genes including draper, ced-12, and the JNK pathway are crucial for this process. When phagocytosis genes are inhibited in the follicle cells, events specifically associated with death of the nurse cells are impaired. Death of the nurse cells is not completely blocked in draper mutants, suggesting that other engulfment receptors are involved. Indeed, we found that the integrin subunit, aPS3, is enriched on stretch follicle cells during late oogenesis and is required for elimination of the nurse cells. Moreover, double mutant analysis revealed that integrins act in parallel to draper. Death of nurse cells in the Drosophila ovary is a unique example of programmed cell death that is both non-apoptotic and non-cell autonomously controlled.

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“…Fly stocks used in this study were as follows: (1) (Han et al, 2014). The lobula Gal4 lines are listed in Table 1.…”

Section: Fly Strainsmentioning

confidence: 99%

Mapping chromatic pathways in the Drosophila visual system

Lin

Luo

Shinomiya

et al. 2015

J of Comparative Neurology

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In Drosophila, color vision and wavelength-selective behaviors are mediated by the compound eye's narrow-spectrum photoreceptors, R7 and R8, and their downstream neurons, Tm5a/b/c and Tm20, in the second optic neuropil, or medulla. These chromatic Tm neurons project axons to a deeper optic neuropil, the lobula, which in insects has been implicated in processing and relaying color information to the central brain. The synaptic targets of the chromatic Tm neurons in the lobula are not known, however. Using a modified GRASP (GFP reconstitution across synaptic partners) method to probe connections between the chromatic Tm neurons and 28 known and novel types of lobula neurons, we identified anatomically the visual projection neurons LT11 and LC14, and the lobula intrinsic neurons Li3 and Li4, as synaptic targets of the chromatic Tm neurons. Single-cell GRASP analyses revealed that Li4 receives synaptic contacts from over 90% of all four types of chromatic Tm neurons while LT11 is postsynaptic to the chromatic Tm neurons with only modest selectivity and at a lower frequency and density. To visualize synaptic contacts at the ultrastructural level, we developed and applied a "two-tag" double labeling method to label LT11's dendrites and the mitochondria in Tm5c's presynaptic terminals. Serial electron microscopic reconstruction confirmed that LT11 receives direct contacts from Tm5c. This method would be generally applicable to map the connections of large complex neurons in Drosophila and other animals. Graphical Abstract CONFLICT OF INTERESTThe authors declare no conflicts of interest. ROLE OF AUTHORSAll authors had access to all data presented in this study. The authors accept responsibility for the integrity and accuracy of the data and data analysis. Study concept and design: TYL, CHL, IAM. Preparation and acquisition of data: TYL, JL, KS, CYT, ZL. Analysis and interpretation of data: TYL, CHL. Drafting of the manuscript: TYL, IAM, CHL. Using trans-synaptic tracing and ultrastructural "two-tag" double-labeling approaches for EM, the authors identify synaptic targets of first-order chromatic interneurons in the deep visual processing center, the lobula. Lobula intrinsic neuron Li4 and projection neuron LT11 receive parallel chromatic inputs but with differential synaptic densities. HHS Public Access

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Epidermal Cells Are the Primary Phagocytes in the Fragmentation and Clearance of Degenerating Dendrites in Drosophila

Cited by 136 publications

References 70 publications

Drosophila Valosin-Containing Protein is required for dendrite pruning through a regulatory role in mRNA metabolism

Drosophila Valosin-Containing Protein is required for dendrite pruning through a regulatory role in mRNA metabolism

Control of non-apoptotic nurse cell death by engulfment genes in Drosophila

Mapping chromatic pathways in the Drosophila visual system

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