Biology subjects

Besse, F.

Publications and source records attributed to Besse, F..

3 recordsLinked to original sources

bioRxiv2026

Decoupling axonal regrowth and branching through Imp-dependent RNA regulation during neuronal remodeling

Structural remodeling of neuronal projections in response to developmental cues, injury, or disease is essential for adaptive circuit rewiring. This dynamic process, characterized by pruning and regrowth phases, requires the coordinated execution of neurite regrowth and branching to establish functional neuronal circuits. Yet, how these processes are regulated in space and time at the post-transcriptional level remains poorly understood. Here, we identify the conserved RNA-binding protein Imp (IGF2BP) as a central regulator of developmental axonal remodeling in Drosophila CCAP/Bursicon neurons. We show that Imp acts within a restricted time window during late metamorphosis to control both late regrowth and branching of adult CCAP/Bursicon axons. Combining functional approaches, high-resolution imaging and single-molecule mRNA detection, we further show that Imp controls these temporally distinct programs through genetically separable regulatory mechanisms. While axonal elongation is mediated by Imp-dependent stabilization of profilin mRNA, axonal branching is mediated by an independent mechanism that may involve local regulation in axons. Together, our findings demonstrate that axonal regrowth and branching, two morphogenetic events essential for neuronal circuit maturation in vivo, are controlled independently, yet coordinated through a common and conserved post-transcriptional framework. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC="FIGDIR/small/740905v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1ca291corg.highwire.dtl.DTLVardef@15108daorg.highwire.dtl.DTLVardef@11c5741org.highwire.dtl.DTLVardef@1a4773a_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2022

Analysis of pre-symptomatic Drosophila models for ALS and SMA reveals convergent impact on functional protein complexes linked to neuro-muscular degeneration

Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS) share phenotypic and molecular commonalities, including the fact that they can be caused by mutations in ubiquitous proteins involved in RNA metabolism, namely SMN, TDP-43 and FUS. Although this suggests the existence of common disease mechanisms, there is currently no model to explain the resulting motor neuron dysfunction. In this work we generated a parallel set of Drosophila models for adult-onset RNAi and tagged neuronal expression of the fly orthologues of the three human proteins, named Smn, TBPH and Caz, respectively. We profiled nuclear and cytoplasmic bound mRNAs using a RIP-seq approach and characterized the transcriptome of the RNAi models by RNA-seq. To unravel the mechanisms underlying the common functional impact of these proteins on neuronal cells, we devised a computational approach based on the construction of a tissue-specific library of protein functional modules, selected by an overall impact score measuring the estimated extent of perturbation caused by each gene knockdown. Transcriptome analysis revealed that the three proteins do not bind to the same RNA molecules and that only a limited set of functionally unrelated transcripts is commonly affected by their knock-down. However, our integrative approach revealed they exert a concerted effect on protein functional modules, acting through distinct targets. Most strikingly, functional annotation revealed that these modules are involved in critical cellular pathways for motor neurons, including neuromuscular junction function. Furthermore, selected modules were found to be significantly enriched in orthologues of human neuronal disease genes. The results presented here show that SMA and ALS disease-associated genes linked to RNA metabolism functionally converge on neuronal protein complexes, providing a new hypothesis to explain the common motor neuron phenotype. The functional modules identified represent promising biomarkers and therapeutic targets, namely given their alteration in asymptomatic settings.

neuroscience↗

bioRxiv2018

Cooption of antagonistic RNA-binding proteins establishes cell hierarchy in Drosophila neuro-developmental tumors

The mechanisms that govern the hierarchical organization of tumors are still poorly understood, especially in highly heterogeneous neural cancers. Previously, we had shown that aggressive neural tumors can be induced upon dedifferentiation of susceptible intermediate progenitors produced during early development (Narbonne-Reveau et al., 2016). Using clonal analysis, stochastic modelling and single-cell transcriptomics, we now find that such tumors rapidly become heterogeneous, containing progenitors with different proliferative potentials. We demonstrate that tumor heterogeneity emerges from the deregulated transition between two antagonistic RNA-binding proteins, Imp and Syncrip, that switch neural progenitors from a default self-renewing to a differentiation-prone state during development. Consequently, aberrant maintenance of Imp confers a cancer stem cell-like identity as Imp+ progenitors sustain tumor growth while being able to continuously generate Syncrip+ progenitors. The latter exhibit limited self-renewal likely due to Syncrip-mediated metabolic exhaustion. This study provides an example of how a subverted developmental transition establishes a hierarchical tumor.

developmental biology↗