Biology subjects

Lavergne, G.

Publications and source records attributed to Lavergne, G..

3 recordsLinked to original sources

bioRxiv2023

Comprehensive map of ribosomal 2'-O-methylation and C/D box snoRNAs in Drosophila melanogaster

During their maturation, ribosomal RNAs (rRNAs) are decorated by hundreds of chemical modifications that participate in proper folding of rRNA secondary structures and therefore in ribosomal function. Along with pseudouridine, methylation of the 2'-hydroxyl ribose moiety (Nm) is the most abundant modification of rRNAs. The majority of Nm modifications in eukaryotes are placed by Fibrillarin, a conserved methyltransferase belonging to a ribonucleoprotein complex guided by C/D box small nucleolar RNAs (C/D box snoRNAs). These modifications impact interactions between rRNAs, tRNAs and mRNAs, and some are known to fine tune translation rates and efficiency. In this study, we built the first comprehensive map of Nm sites in Drosophila melanogaster rRNAs using two complementary approaches (RiboMethSeq and Nanopore direct RNA sequencing) and identified their corresponding C/D box snoRNAs by whole-transcriptome sequencing. We de novo identified 61 Nm sites, from which 55 are supported by both sequencing methods, we validated the expression of 106 C/D box snoRNAs and we predicted new or alternative rRNA Nm targets for 31 of them. Comparison of methylation level upon different stresses show only slight but specific variations, indicating that this modification is relatively stable in D. melanogaster. This study paves the way to investigate the impact of snoRNA-mediated 2'-O-methylation on translation and proteostasis in a whole organism.

molecular biology↗

bioRxiv2019

New muscle identity code components identified by TRAP control shape and size of muscle subsets in Drosophila

A combinatorial code of identity transcription factors (iTFs) specifies the diversity of muscle types in Drosophila. We previously showed that two iTFs, Lms and Ap, play critical role in the identity of a subset of larval body wall muscles, the lateral transverse (LT) muscles. Intriguingly, a small portion of ap and lms mutants displays an increased number of LT muscles, a phenotype that recalls pathological split muscle fibers in human. However, genes acting downstream of Ap and Lms to prevent these aberrant muscle feature are not known. Here, we applied a cell type specific translational profiling (TRAP) to identify gene expression signatures underlying identity of muscle subsets including the LT muscles. We found that Gelsolin (Gel) and dCryAB, both encoding actin-interacting proteins, displayed LT muscle prevailing expression positively regulated by, the LT iTFs. Loss of dCryAB function resulted in LTs with irregular shape and occasional branched ends also observed in ap and lms mutant contexts. In contrast, enlarged and then split LTs with a greater number of myonuclei formed in Gel mutants while Gel gain of function resulted in unfused myoblasts, collectively indicating that Gel regulates LTs size and prevents splitting by limiting myoblast fusion. Thus, dCryAB and Gel act downstream of Lms and Ap and contribute to preventing LT muscle branching and splitting. Our findings offer first clues to still unknown mechanisms of pathological muscle splitting commonly detected in human dystrophic muscles and causing muscle weakness.

developmental biology↗

bioRxiv2019

Drosophila adult muscle precursor cells contribute to motor axon pathfinding and proper innervation of embryonic muscles

Adult Muscle Precursors (AMPs), the Drosophila muscle stem cells, arise from the asymmetric cell divisions of a subset of muscle progenitors ([1]) and are characterized by the persistent expression of the myogenic transcription factor Twist ([2]) and activation of the Notch pathway ([3]; [4]). They occupy stereotyped positions in the vicinity of developing body wall muscles, stay quiescent and undifferentiated during embryonic life and are reactivated during second larval instar ([5]; [6]) to generate muscles of the adult fly. Strikingly, AMPs are also located in the path of intersegmental (ISN) and segmental (SN) motor neuron branches ([2]; [7]). However, their role and interactions with the motor neurons have not yet been analyzed in details. Here, using AMP sensor line revealing cell membrane extensions we show that the navigating ISN first contacts the dorso-lateral (DL-AMPs) and then the dorsal AMP (D-AMP) marking the end of its trajectory. In parallel, the segmental nerve SNa innervating lateral muscles targets the lateral AMPs (L-AMPs). In vivo analyses of AMPs behavior highlight an active filopodial dynamic of AMPs toward the ISN and SNa suggesting they could guide motor axons and contribute to muscle innervations. Indeed, our data show that loss or mispositioning of L-AMPs affect the SNa motor axons pathfinding and branching, leading to loss or aberrant muscle innervation. The finding of a transient expression of the guidance molecule Sidestep in L-AMPs suggests its implication in this process. Thus, proper muscle innervation does not only rely on the dialogue between the motor neurons and the muscles, but also on the AMP cells. AMPs represent spatial landmarks for navigating motor neurons and their positioning is critical for the muscles innervation in the lateral region.

developmental biology↗