Biology subjects

Nicolas, M.

Publications and source records attributed to Nicolas, M..

8 recordsLinked to original sources

bioRxiv2026

The miR319-targeted TCP transcription factors play crucial roles in the establishment of Arabidopsis thaliana shoot architecture in response to carbon and nitrogen availability.

Shoot branching is a highly plastic developmental process that allows plants to adjust their architecture to environmental conditions, such as carbon and nitrogen availability. Although the class II TCP transcription factor BRANCHED1 is a well-established repressor of shoot branching, the contribution of other TCP factors during this process remains less well understood. Here, we show that the miR319-targeted TCP module promotes shoot branching in Arabidopsis thaliana. Overexpression of miR319 reduced rosette branch production, whereas repression of TCP3 activity or triple knockout (KO) mutation in TCP3, TCP4 and TCP10 inhibited branching. Conversely, expression of a miR319-resistant TCP3 triggered a highly branched phenotype, indicating that TCP3 and related miR319 targets act as positive regulators of shoot branching. Genetic analysis with the strigolactone-deficient max4 mutant showed that strigolactones mediate, at least partly, the reduced branching observed in the miR319 overexpressing line and in the tcp3,4,10 triple mutant. Transcriptomic and DNA-binding analyses indicated indirect effect of TCP3 on strigolactone biosynthesis genes. Instead, miR319 overexpression increased the sensitivity of branching to nitrogen limitation and reduced nitrate uptake, thereby increasing the expression of strigolactone synthesis genes. We further show that carbon starvation reduced the transcription levels of miR319-targeted TCPs, independently of miR319 accumulation, and that TCP3 may connect carbon availability to sugar signalling via HEXOKINASE1. Together, our results identify the miR319-targeted TCP module as a positive regulator of shoot branching that links plant architecture to carbon and nitrogen availability.

plant biology↗

bioRxiv2026

Integrated Collagen Architecture and Composition Improve Risk Stratification in Triple-Negative Breast Cancer

PurposeTriple-negative breast cancer (TNBC) exhibits substantial clinical heterogeneity, with some patients experiencing early recurrence and poor survival despite similar clinicopathologic features. We sought to determine whether quantitative measures of intratumoral collagen architecture and composition derived from standard histopathologic specimens can identify patients at risk of recurrence and adverse survival outcomes. Experimental DesignWe analyzed a retrospective cohort of 79 TNBC tumors assembled into a tissue microarray using a multimodal computational pathology framework integrating Massons Trichrome staining with COL1 and COL3 immunohistochemistry. Collagen architecture was quantified using fiber-based image analysis and unsupervised clustering, while collagen composition was assessed using a normalized COL3:COL1 ratio. Associations with recurrence-free interval (RFI) and overall survival (OS) were evaluated using Kaplan-Meier analysis, restricted mean survival time (RMST), and Cox proportional hazards modeling. ResultsUnsupervised analysis identified four distinct collagen architectural states, which were consolidated into low-risk and high-risk groups based on recurrence patterns. High-risk collagen architecture was associated with significantly worse long-term RFI (log-rank p=0.025; RMST difference 10.1 months). Independently, a higher COL3:COL1 ratio was associated with improved OS (log-rank p=0.042; RMST difference 9.4 months). Integration of architectural and compositional biomarkers further refined risk stratification, identifying a subgroup with high-risk architecture and low COL3:COL1 ratio that exhibited the poorest survival outcomes. Notably, collagen-based stratification identified patients with divergent outcomes not readily predicted from tumor stage alone. ConclusionsQuantitative assessment of intratumoral collagen architecture and composition provides clinically meaningful prognostic information in TNBC and enables stratification of recurrence and survival risk. These findings support extracellular matrix phenotyping as a practical and scalable computational pathology approach for refining risk assessment in TNBC. Translational RelevanceTriple-negative breast cancer (TNBC) remains clinically challenging due to heterogeneous outcomes that are not fully captured by standard clinicopathologic variables. In this study, we demonstrate that quantitative features of intratumoral collagen architecture and composition, derived from routine pathology specimens, provide clinically meaningful prognostic information. Collagen-based biomarkers, including distinct collagen architectural phenotypes and the COL3:COL1 ratio, identify patient subgroups with distinct recurrence and survival outcomes, particularly among individuals whose risk is not adequately predicted by conventional staging. Importantly, these features can be extracted from widely available histological stains and immunohistochemistry, supporting the potential integration into existing pathology workflows. These findings support the tumor microenvironment as an underutilized source of biomarkers and suggest that extracellular matrix-based phenotyping may improve risk stratification and inform clinical decision-making in TNBC.

cancer biology↗

bioRxiv2025

Molecular mechanisms underlying the determination of axillary bud fate and outgrowth into branch crown in strawberry

{blacksquare} In strawberry, the axillary bud (AXB) can produce either an elongated stem called stolon giving a daughter-plant (asexual reproduction) or an inflorescence-bearing branch crown (BC) (sexual reproduction). The fate of the AXB depends on node position on the axis and on genetic and environmental factors. Here, in Fragaria vesca, we addressed the largely unanswered question of how molecular factors determine AXB fate. {blacksquare}To get insights into the mechanisms already at play in a morphologically indistinguishable (undifferentiated) AXB, depending on its fate, we combined (1) the phenotypic characterization of AXB development throughout plant growth with (2) the RNA-seq analysis of undifferentiated AXBs, using three different genotypes producing either BCs or stolons (fvetfl1 and fvega20ox mutants, FveFT3 overexpressor). {blacksquare}Results allowed the identification of genes regulating AXB fate and outgrowth, among which FveBRC1. The analysis of FveBRC1 expression in genotypes combining various traits (perpetual/seasonal flowering; runnering/runneless) and the generation of CRISPR/Cas9 brc1 mutants further demonstrated that FveBRC1 plays a central role in the determination of AXB fate in strawberry, in addition to its well-known function in BC outgrowth. {blacksquare}These original results provide new insights into the determination of AXB fate and, consequently, the control of fruit yield in strawberry.

plant biology↗

bioRxiv2025

Multifaceted conserved functions of Notch during post-embryonic neurogenesis in the annelid Platynereis

Notch signaling is an evolutionarily conserved pathway known to orchestrate neurogenesis by regulating the transition of progenitor cells to differentiated neurons and glia, as well as by directing neurite outgrowth and axon guidance in many species. Although extensively studied in vertebrates and ecdysozoans, the role of Notch in spiralians (including mollusks, annelids or flatworms) remains largely unexplored, limiting our understanding of its conserved functions across bilaterians. In this study, we focus on the segmented annelid Platynereis dumerilii, a model organism in neurobiology and regeneration, to investigate Notch signaling functions during post-embryonic developmental processes. We show that Notch pathway components are expressed in neurogenic territories during both posterior elongation and regeneration, two processes requiring sustained neurogenesis. Through chemical inhibitions of the pathway and RNA-seq profiling, we demonstrate that Notch signaling regulates neural progenitor specification, differentiation, and overall neurogenic balance in the regenerating and elongating posterior part. Moreover, disruption of Notch activity leads to severe defects in pygidial and central nervous system organization, including abnormal axon guidance and impaired neurite outgrowth. Altogether, our results support the hypothesis that Notch has multifaceted conserved functions in neurogenesis across bilaterians, shedding light on the ancestral functions of this critical pathway.

developmental biology↗

bioRxiv2024

Potato cultivars use different root physiological and molecular mechanisms to acclimate to salt stress

O_LISoil salinity induces osmotic stress and ion toxicity in plants, detrimentally affecting their growth and development. Potato (Solanum tuberosum) faces yield reductions due to salt stress. The mechanisms of salt stress resilience, especially in adventitious roots, remain unknown. C_LIO_LIWe investigated the resilience of three potato cultivars - Desiree, Innovator, and Mozart - by studying their physiological and transcriptomic responses to salt stress. C_LIO_LIOur findings reveal that under salt stress, the growth of stolons and stolon node roots is similarly reduced unlike tubers, even though they are physically connected. Surprisingly, tubers accumulate Cl- but not Na+ under salt stress, suggesting an active Na+ exclusion mechanism. Innovator showed the lowest suberin and lignin deposition before salt stress and higher K+ leakage, leading to a stronger initial stress response with high ABA content and a distinct transcriptomic pattern. Nevertheless, Innovator was the most resilient, displaying lower growth, salt-tolerance index and tuber yield reduction. Transcriptomic analysis revealed several K+/Na+ channel genes which might regulate ions homeostasis during salt stress, in particular in Innovator. C_LIO_LIAltogether, we conclude that acclimation ability, rather than initial protection of roots against salt, prevails in long term salt-stress resilience of potato. C_LI

plant biology↗

bioRxiv2021

Ureter single-cell and spatial mapping reveal cell types, architecture, and signaling networks

Tissue engineering offers a promising treatment strategy for ureteral strictures, but its success requires an in-depth understanding of the architecture, cellular heterogeneity, and signaling pathways underlying tissue regeneration. Here we define and spatially map cell populations within the human ureter using single-cell RNA sequencing, spatial gene expression, and immunofluorescence approaches. We focused on the stromal and urothelial cell populations to enumerate distinct cell types composing the human ureter and inferred potential cell-cell communication networks underpinning the bi-directional crosstalk between these compartments. Furthermore, we analyzed and experimentally validated the importance of Sonic Hedgehog (SHH) signaling pathway in adult stem cell maintenance. The SHH-expressing basal cells supported organoid generation in vitro and accurately predicted the differentiation trajectory from basal stem cells to terminally differentiated umbrella cells. Our results highlight essential processes involved in adult ureter tissue homeostasis and provide a blueprint for guiding ureter tissue engineering.

developmental biology↗

bioRxiv2021

The Amyloid Precursor Protein is a conserved Wnt receptor

The Amyloid Precursor Protein (APP) and its homologues are transmembrane proteins required for various aspects of neuronal development and activity, whose molecular function is unknown. Specifically, it is unclear whether APP acts as a receptor, and if so what its ligand(s) may be. We show that APP binds the Wnt ligands Wnt3a and Wnt5a and that this binding regulates APP protein levels. Wnt3a binding promotes full length APP (flAPP) recycling and stability. In contrast, Wnt5a promotes APP targeting to lysosomal compartments and reduces flAPP levels. A conserved Cysteine Rich Domain (CRD) in the extracellular portion of APP is required for Wnt binding, and deletion of the CRD abrogates the effects of Wnts on flAPP levels and trafficking. Finally, loss of APP results in increased axonal and reduced dendritic growth of mouse embryonic primary cortical neurons. This phenotype can be cell-autonomously rescued by full length, but not CRD-deleted, APP.

cell biology↗

bioRxiv2017

Post-transcriptional modulation of Dscam1 enhances axonal growth in development and after injury

Injury to the adult central nervous systems (CNS) results in severe long-term disability because damaged CNS connections rarely regenerate. Although several axon regeneration regulators have been proposed, intrinsic regenerative mechanisms remain largely unexplored. Here, we use a Drosophila CNS injury model to identify a novel pro-regeneration signaling pathway. We conducted a genetic screen of approximately three hundred candidate genes and identified three strong inducers of axonal growth and regeneration: the Down Syndrome Cell Adhesion Molecule (Dscam1), the de-ubiquitinating enzyme Fat Facets (Faf)/Usp9x and the Jun N-Terminal Kinase (JNK) pathway transcription factor Kayak (Kay)/Fos. Genetic and biochemical analyses link these genes in a common signaling pathway whereby Faf stabilizes Dscam1 protein levels, by acting on the 3-UTR of its mRNA, and Dscam1 acts upstream of the growth-promoting JNK signal. The mammalian homolog of Faf, Usp9x/FAM, shares both the regenerative and Dscam1 stabilizing activities, suggesting a conserved mechanism.

neuroscience↗