Biology subjects

Arnaud, N.

Publications and source records attributed to Arnaud, N..

5 recordsLinked to original sources

bioRxiv2026

The CUP-SHAPED COTYLEDON 2 - MIR164A regulatory feedback loop directs leaf morphogenesis

Gene regulatory networks (GRNs) establish the spatio-temporal gene expression patterns necessary for reproducible development of organisms. MicroRNAs have emerged as important regulators of gene expression controlling either target gene levels, spatial patterns or timing. These molecular functions may vary depending on how they are integrated into GRNs. Here we used the Arabidopsis leaf as a model to study the genetic and molecular interactions between the CUP-SHAPED COTYLEDON 2 (CUC2) transcription factor and its negative regulator, miR164A. Quantitative morphometric analyses showed that miR164A acts from early stages during leaf development regulating CUC2 expression dynamic rather than the spatial distribution of CUC2. At the molecular level, CUC2 directly activates MIR164A expression, forming a single negative feedback loop. Further, using a ratiometric approach, we identified a cis-regulatory element (CRE) sufficient to drive CUC2-dependent MIR164A expression at the leaf sinus. Ordinary differential equation (ODE) modelling suggests that CUC2-CRE may control the timely accumulation of CUC2. Accordingly, quantification of CUC2 protein accumulation dynamics using a spatio-temporal mean cartography strategy in CRISPR cis-regulatory variants at the MIR164A locus revealed that CUC2-dependent MIRA164A expression is required to maintain both the precise timing of CUC2 expression and CUC2 levels. Altogether, our work provides experimental evidence for a specific role of the CUC2-MIR164A module in shaping leaf development, highlighting the contribution of network topology to GRN functions.

plant biology↗

bioRxiv2026

Universally conserved isoasparylation sustains ribosome biogenesis and function

All living beings use ribosomes to synthesize proteins from -amino acids. Inherited from our common ancestor, a few universally conserved ribosome biogenesis steps, introducing essential ribosomal RNA modifications, have survived to our days. However, it was unknown whether similar primordial core mechanisms could also target ribosomal proteins. Here we show that the assembly and the function of ribosomes depend on the installation of an unusual {beta}-amino acid, isoaspartate, within the ribosomal protein uS11. In bacteria, mitochondria, and plastids, this modification is catalyzed by the metzincin-like hydrolase YbeY, whereas in archaea and eukaryotes, it is introduced by the atypical kinase Fap7. The formation of this strategically positioned isoaspartate enables correct maturation of the small ribosomal subunit to support protein synthesis and normal cell physiology.

biochemistry↗

bioRxiv2024

Developmental rewiring of the NGAL/CUC/KLU network associated with pleiotropic roles of NGAL genes

Gene Regulatory Networks (GRNs) play prominent roles in regulating developmental processes, and their modulation across species is a major source for evolutionary innovation. However, it remains poorly understood how GRNs are rewired between different organs within a single species. This question is particularly relevant for pleiotropic genes, which may exhibit organ-specific GRN modulations potentially reflecting their diverse functions. To address this, we investigated the NGATHA-like (NGAL) genes, as a model for pleiotropic genes that regulate growth or patterning in multiple Arabidopsis organs via two distinct pathways involving the CUP-SHAPED COTYLEDON (CUC) and KLUH (KLU) genes. By combining genetic analysis with gene expression characterization, we uncovered significant organ-specific rewiring of the NGAL/CUC/KLU regulatory module. Our findings highlight that changes in gene expression patterns, potentially arising from developmental constraints, play a pivotal role in the organ-specific modulation of GRNs. Furthermore, GRNs at the molecular and functional levels do not always align perfectly, potentially due to the influence of additional regulatory mechanisms. Altogether, our findings reveal significant modulation of the GRNs associated with pleiotropic genes. We propose that this flexibility in GRNs facilitates gene pleiotropy.

plant biology↗

bioRxiv2021

A cell wall-associated gene network shapes leaf boundary domains

Boundary domains delimit and organize organ growth throughout plant development almost relentlessly building plant architecture and morphogenesis. Boundary domains display reduced growth and orchestrate development of adjacent tissues in a non-cell autonomous manner. How these two functions are achieved remains elusive despite the identification of several boundary-specific genes. Here, we show using morphometrics at the organ and cellular levels that leaf boundary domain development requires SPINDLY (SPY), an O-fucosyltransferase, to act as cell growth repressor. Further we show that SPY acts redundantly with the CUP-SHAPED COTYLEDON transcription factors (CUC2 and CUC3), which are major determinants of boundaries development. Accordingly at the molecular level, CUC2 and SPY repress a common set of genes involved in cell wall loosening providing a molecular framework for the growth repression associated with boundary domains. Atomic force microscopy (AFM) confirmed that young leaf boundary domain cells have stiffer cell walls than marginal outgrowth. This differential cell wall stiffness was reduced in spy mutant. Taken together our data reveal a concealed CUC2 cell wall associated gene network linking tissue patterning with cell growth and mechanics. Summary statementDecreased cell-wall loosening gene expression contributes to the coordination of cell growth and mechanics with tissue patterning thus driving boundary development.

plant biology↗

bioRxiv2018

Reproducing Transformation of Indolent B-cell Lymphoma by T-cell Immunosuppression of L.CD40 Mice.

Transformation of an indolent B-cell lymphoma is associated with a more aggressive clinical course and poor survival. The role of immune surveillance in the transformation of a B-cell indolent lymphoma towards a more aggressive form is poorly documented. To experimentally address this question, we used the L.CD40 mouse model, which is characterized by B-cell specific continuous CD40 signaling, responsible for spleen indolent clonal or oligoclonal B-cell lymphoma after one year in 60% cases. Immunosuppression was obtained either by T/NK cell depletion or by treatment with the T-cell immunosuppressive drug cyclosporin A. Immunosuppressed L.CD40 mice had larger splenomegaly with increased numbers of B-cells in both spleen and peripheral blood. High-throughput sequencing of immunoglobulin variable segments revealed that clonal expansion was increased in immunosuppressed L.CD40 mice. Tumor B cells of immunosuppressed mice were larger with an immunoblastic aspect, both on blood smears and spleen tissue sections, with increased proliferation rate and increased numbers of activated B-cells. Collectively, these features suggest that immune suppression induced a shift from indolent lymphomas into aggressive ones. Thus, as a preclinical model, immunosuppressed L.CD40 mice reproduce aggressive transformation of an indolent B-cell tumor and highlight the role of the immune surveillance in its clinical course, opening new perspective for immune restoration therapies.\n\nSummary statementHighlighting the role of immune surveillance, transformation of indolent B-cell lymphoma into an aggressive malignancy is experimentally reproduced after T-cell immune suppression in the L.CD40 preclinical mouse model.

cancer biology↗