Biology subjects

Llobet Rosell, A.

Publications and source records attributed to Llobet Rosell, A..

2 recordsLinked to original sources

bioRxiv2023

Local translation is required for sustained circuit integrity in impaired Wallerian degeneration

After injury, the severed axon separated from the soma activates programmed axon degeneration, an evolutionarily conserved pathway to initiate its degeneration within a day. Conversely, severed projections deficient in programmed axon degeneration remain morphologically preserved with functional synapses for weeks to months after injury. How this synaptic function is sustained remains currently unknown. Here, we demonstrate that dNmnat-mediated over-expression attenuates programmed axon degeneration in distinct neuronal populations. Severed projections remain morphologically preserved for weeks after injury. When evoked, they elicit a postsynaptic behavior which is a readout for preserved synaptic function. We used ribosomal pulldown to isolate translatomes from these projections. Transcriptional profiling revealed several enriched biological classes. Identified candidates were validated in a screen using a novel system to automatically quantify evoked antennal grooming behavior as a proxy for preserved synaptic function. We used RNAi-mediated knockdown to identify mTOR as a mediator of local protein synthesis, and specifically candidates involved in protein ubiquitination and calcium homeostasis, required for preserved synaptic function. Our dataset uncovered several uncharacterized genes linked to human diseases. It may therefore offer insights into novel avenues for therapeutic treatments.

neuroscience↗

bioRxiv2022

Neuron secreted chemokine-like Orion is involved in the transformation of glial cells into phagocytes in different neuronal remodeling paradigms

During animal development, neurons often form exuberant or incorrect axons and dendrites at early stages, followed by the refinement of neuronal circuits at late stages. Neural circuit refinement leads to the production of large amounts of neuronal debris in the form of neuronal cell corpses, fragmented axons and dendrites, and pruned synapses requiring disposal. In particular, the predominant phagocytes acting during the neuronal remodeling and degeneration are glial cells and critical signaling pathways between neurons and glia leading to phagocytosis are required. Chemokine-like mushroom body neuron secreted Orion ligand was shown to be essential to the astrocyte infiltration into the {gamma} axon bundle leading to {gamma} axon pruning and clearance of debris left from axon fragmentation. Here we show a role of orion also in debris engulfment and phagocytosis. Interestingly, we show that orion is also involved in the overall transformation of astrocytes into phagocytes. In addition, analysis of several neuronal paradigms demonstrates the role of orion in the elimination of both peptidergic vCrz+ and PDF-Tri neurons via additional phagocytic glial cells as cortex and/or ensheathing glia. Our results suggest that Orion is essential for phagocytic activation of three different types of glial cells: astrocytes, cortex and ensheathing glia and point to Orion as a trigger not only of glial infiltration but also engulfment and phagocytosis.

neuroscience↗