Biology subjects

Thetiot, M.

Publications and source records attributed to Thetiot, M..

5 recordsLinked to original sources

bioRxiv2026

mTORC1 supports progression toward activation competence in quiescent adult neural stem cells

Neural stem cells (NSCs) sustain lifelong neurogenesis through the tight regulation of quiescence, self-renewal and differentiation. Quiescent NSCs (qNSCs) exist in distinct substates, ranging from deep to shallow quiescence, yet the mechanisms governing these transitions remain unclear. In long-term self-renewing NSCs of the adult zebrafish pallium, we show that mTORC1 activity is specifically enriched during a prolonged quiescence phase in which NSCs acquire activation competence. Functional perturbations, analyzed in situ and using single-cell RNA sequencing, reveal that mTORC1 regulates cell progression during this phase, concomitantly ensuring the correct tempo for NSC transition towards activation and the preservation of stemness. These findings challenge the classical view of mTORC1 as a simple regulator of proliferation and identify it as a key regulator of NSC quiescence heterogeneity and dynamics under physiological conditions. By coordinating stemness maintenance with activation competence, mTORC1 emerges as a central player balancing long-term NSC preservation with neurogenic output in the adult brain.

cell biology↗

bioRxiv2024

Neuronal activity promotes axonal node-like clustering prior to myelination and remyelination in the central nervous system.

Nodes of Ranvier ensure the fast saltatory conduction along myelinated axons, through their enrichment in voltage-gated sodium and potassium channels. We and others have shown that node-like cluster assembly can occur before myelination. In multiple sclerosis, demyelination is associated with node of Ranvier disassembly, but node-like reassembly can occur prior to remyelination. Given the crucial role of neuronal activity in inducing (re)myelination, we asked whether neuronal activity could regulate node-like clustering. We show that node-like clustering is promoted by neuronal activity and decreased when excitatory glutamatergic receptors are inhibited. Altering glutamatergic neurotransmission leads to the downregulation of Nav1.1 expression, which we show to be critical for node-like clustering. Neuronal activity also promotes node-like clustering in remyelination. As node-like clusters modulate conduction velocity and myelination initiation along axons, we propose that activity-dependent node-like clustering could modulate neuronal network establishment, as well as myelination regulation and patterning during development, plasticity and repair.

neuroscience↗

bioRxiv2023

Prosaposin maintains adult neural stem cells in a state associated with deep quiescence

In most vertebrates, adult neural stem cells (NSCs) continuously give rise to neurons in discrete brain regions. A critical process for maintaining NSC pools over long periods of time in the adult brain is NSC quiescence, a reversible and tightly regulated state of cell cycle arrest. Recently, lysosomes were identified to regulate the NSC quiescence-proliferation balance. However, it remains controversial whether lysosomal activity promotes NSC proliferation or quiescence, and a finer influence of lysosomal activity on NSC quiescence duration or depth remains unexplored. Using RNA-sequencing and pharmacological manipulations, we show that lysosomes are necessary for NSC quiescence maintenance. Additionally, we reveal that expression of psap, encoding the lysosomal regulator Prosaposin, is enriched in quiescent NSCs (qNSCs) that reside upstream in the NSC lineage and display a deep/long quiescence phase in the adult zebrafish telencephalon. We show that shRNA-mediated psap knock-down increases the proportion of activated NSCs (aNSCs) as well as NSCs that reside in shallower quiescence states (signed by ascl1a and deltaA expression). Collectively, our results identify the lysosomal protein Psap as a (direct or indirect) quiescence regulator and unfold the interplay between lysosomal function and NSC quiescence heterogeneities.

neuroscience↗

bioRxiv2020

Microglia-neuron communication at nodes of Ranvier depends on neuronal activity through potassium release and contributes to myelin repair.

Microglia, the resident immune cells of the central nervous system, are key players in healthy brain homeostasis and plasticity. In neurological diseases, such as Multiple Sclerosis, activated microglia either promote tissue damage or favor neuroprotection and myelin regeneration. The mechanisms for microglia-neuron communication remain largely unkown. Here, we identify nodes of Ranvier as a direct and stable site of interaction between microglia and axons, in both mouse and human tissue. Using dynamic imaging, we highlight the preferential interaction of microglial processes with nodes of Ranvier along myelinated fibers. We show that microglianode interaction is modulated by neuronal activity and associated potassium release, with THIK-1 ensuring their microglial read-out. Disrupting axonal K+ flux following demyelination polarizes microglia towards a pro-inflammatory phenotype and decreases remyelination rate. Taken together, these findings identify the node of Ranvier as a major site for microglia-neuron communication, participating in the pro-remyelinating effect of microglia after myelin injury.

neuroscience↗

bioRxiv2019

An alternative mechanism of early nodal clustering and myelination onset in GABAergic neurons of the central nervous system

In vertebrates, fast saltatory conduction along myelinated axons relies on the node of Ranvier. How nodes assemble on CNS neurons is not yet fully understood. We recently highlighted that clusters similar to nodes can form prior to myelin deposition in hippocampal GABAergic neurons and are associated with increased conduction velocity. Here, we used a live imaging approach to characterize the intrinsic mechanisms underlying the assembly of these early clusters. We first demonstrated that their components can partially pre-assemble prior to membrane targeting and determined the molecular motors involved in their trafficking. We then demonstrated the key role of the protein {beta}2Nav for clustering initiation. We further unraveled the fate of these early clusters, by showing that they participate in node formation, but also have an unexpected role in guiding oligodendrocyte processes prior to myelin deposition. Altogether our results shed light on an alternative mechanism of nodal clustering and myelination onset.

neuroscience↗