Developmental pruning of sensory neurites by mechanical tearing in Drosophila

Abstract

Mechanical forces actively shape cells during development, but little is known about their roles during neuronal morphogenesis. Developmental neurite pruning, a critical circuit specification mechanism, often involves neurite abscission at predetermined sites by unknown mechanisms. Pruning of Drosophila sensory neuron dendrites during metamorphosis is triggered by the hormone ecdysone, which induces local disassembly of the dendritic cytoskeleton. Subsequently, dendrites are severed at positions close to the soma by an unknown mechanism. We found that ecdysone signaling causes the dendrites to become mechanically fragile. Severing occurs during periods of increased pupal morphogenetic tissue movements, which exert mechanical forces on the destabilized dendrites. Tissue movements and dendrite severing peak during pupal ecdysis, a period of strong abdominal contractions, and abolishing ecdysis causes non-cell autonomous dendrite pruning defects. Thus, our data establish mechanical tearing as a novel mechanism during neurite pruning.

Astrocyte-dependent local neurite pruning and Hox gene-mediated cell death in Beat-Va neurons

“…Why a role for neuron-autonomous EcR signaling is more fully revealed when astrocytes are also blocked from transformation is an open question. A recent study showed that neuronal ecdysone signaling allows ddaC neurons to become competent for pruning by driving microtubule rearrangement, with subsequent physical force caused by tissue movement in the body wall during metamorphosis driving the severing and fragmentation of dendrites (Krämer, Wolterhoff et al 2023). It is possible that neuronal ecdysone signaling may make Beat-Va M neurons competent for remodeling through similar mechanisms, but execution of fragmentation requires a secondary mechanical event.…”

Recent progress in dendritic pruning of Drosophila C4da sensory neurons

“…Dendrite severing in the C4da neurons takes place during the period of elevated movements of pupal tissue, which applies mechanical forces to break dendrites. This suggests that mechanical tearing may be a novel mechanism underlying dendrite pruning [ 62 ]. It has been found that the axons and proximal regions of dendrites in C4da neurons are encapsulated by peripheral glial cells [ 63 ], and thus mechanical dendritic dissection during pruning may be affected by these surrounding cells.…”

TORC1 regulation of dendrite regrowth after pruning is linked to actin and exocytosis

“…Cell biological pathways underlying neurite pruning therefore must involve mechanisms for spatial regulation of neurite destruction and maintenance. This spatial aspect of pruning may in part be due to cytoskeleton regulation [ 2 ] and tissue mechanical aspects [ 3 ]. Following pruning, remodeling neurons often regrow new neurites with a morphology adapted to subsequent developmental stages.…”