Proapoptotic RHG proteins and mitochondria are required for sensory dendrite pruning in Drosophila
Abstract
Caspases are best known for their role in apoptosis, but they are also deployed sub-lethally during development, where they contribute to cell fate specification, migration and terminal differentiation. How neurons activate executioner caspases without dying remains unresolved. At the onset of Drosophila metamorphosis, neighbouring sensory neurons in the dorsal body wall adopt opposite fates: class III dendritic arborization (da) neurons die by apoptosis, while the class IV da neuron ddaC prunes its larval dendrites before regrowing an adult-specific arborization. Their proximity allows lethal and non-lethal caspase signalling to be compared side by side in an intact animal. Using SR4VH, a sensitive dual-colour executioner caspase probe, we show that caspase substrates are cleaved in ddaC within 20 min of puparium formation, well before the proximal dendrites are severed, and at consistently lower levels than in its dying neighbours. Single-cell H99 mutant clones reveal that the proapoptotic RHG proteins are cell-autonomously required for pruning. Although reaper, hid and grim are all transcribed in ddaC as remodelling begins, mutant combinations suggest that reaper and grim, rather than hid, cooperate to drive branch severing and clearance. In addition, disrupting mitochondrial function or transport depletes dendritic mitochondria, prevents caspase activation, and blocks both pruning in ddaC and apoptosis in neighbouring class III neurons. Taken together, our data show that Reaper and Grim are required cell-autonomously for pruning, and that mitochondria are required for both caspase activation and branch severing.
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BibTeX
@article{mukherjee2026proapoptotic,
title = {{Proapoptotic RHG proteins and mitochondria are required for sensory dendrite pruning in Drosophila}},
author = {Amrita Mukherjee and Ryan Pei-Yen Cheng and Connor J. Sproston and Sinziana Pop and Shu Kondo and Darren W. Williams},
journal = {Scientific Reports},
year = {2026},
month = nov,
doi = {10.1038/s41598-026-77081-9},
url = {https://www.nature.com/articles/s41598-026-77081-9},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Proapoptotic RHG proteins and mitochondria are required for sensory dendrite pruning in Drosophila
AU - Amrita Mukherjee
AU - Ryan Pei-Yen Cheng
AU - Connor J. Sproston
AU - Sinziana Pop
AU - Shu Kondo
AU - Darren W. Williams
PY - 2026
DA - 2026/11/03
JO - Scientific Reports
DO - 10.1038/s41598-026-77081-9
UR - https://www.nature.com/articles/s41598-026-77081-9
AB - Caspases are best known for their role in apoptosis, but they are also deployed sub-lethally during development, where they contribute to cell fate specification, migration and terminal differentiation. How neurons activate executioner caspases without dying remains unresolved. At the onset of Drosophila metamorphosis, neighbouring sensory neurons in the dorsal body wall adopt opposite fates: class III dendritic arborization (da) neurons die by apoptosis, while the class IV da neuron ddaC prunes its larval dendrites before regrowing an adult-specific arborization. Their proximity allows lethal and non-lethal caspase signalling to be compared side by side in an intact animal. Using SR4VH, a sensitive dual-colour executioner caspase probe, we show that caspase substrates are cleaved in ddaC within 20 min of puparium formation, well before the proximal dendrites are severed, and at consistently lower levels than in its dying neighbours. Single-cell H99 mutant clones reveal that the proapoptotic RHG proteins are cell-autonomously required for pruning. Although reaper, hid and grim are all transcribed in ddaC as remodelling begins, mutant combinations suggest that reaper and grim, rather than hid, cooperate to drive branch severing and clearance. In addition, disrupting mitochondrial function or transport depletes dendritic mitochondria, prevents caspase activation, and blocks both pruning in ddaC and apoptosis in neighbouring class III neurons. Taken together, our data show that Reaper and Grim are required cell-autonomously for pruning, and that mitochondria are required for both caspase activation and branch severing.
SN - 2045-2322
ER -