Biology subjects

Burguet, J.

Publications and source records attributed to Burguet, J..

4 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↗

bioRxiv2022

De novo stem cell establishment in meristems requires repression of organ boundary cell fate

Stem cells play important roles in animal and plant biology as they sustain morphogenesis and tissue replenishment following aging or injuries. In plants, stem cells are embedded in multicellular structures called meristems and the formation of new meristems is essential for the plastic expansion of the highly branched shoot and root systems. In particular, axillary meristems that produce lateral shoots arise from the division of boundary domain cells at the leaf base. The CUP-SHAPED COTYLEDON (CUC) genes are major determinants of the boundary domain and are required for axillary meristem initiation. However, how axillary meristems get structured and how stem cells become established de novo remains elusive. Here, we show that two NGATHA-LIKE transcription factors, DPA4 and SOD7, redundantly repress CUC expression in the initiating axillary meristem. Ectopic boundary fate leads to abnormal growth and organisation of the axillary meristem and prevents de novo stem cell establishment. Floral meristems of the dpa4 sod7 double mutant show a similar delay in stem cell de novo establishment. Altogether, while boundary fate is required for the initiation of axillary meristems, our work reveals how it is later repressed to allow proper meristem establishment and de novo stem cell niche formation.

plant biology↗

bioRxiv2019

Endothelial CXCL5 negatively regulates myelination and repair after white matter stroke

Cerebral small vessel disease and resulting white matter pathologies are worsened by cardiovascular risk factors including obesity. The molecular changes in cerebral endothelial cells caused by chronic cerebrovascular risk factors remain unknown. We developed a novel approach for molecular profiling of chronically injured cerebral endothelial cells using cell-specific translating ribosome affinity purification (RiboTag) with RNA-seq in Tie2-Cre:RiboTag mice. We used this approach to identify the transcriptome of white matter endothelial cells after the onset of diet-induced obesity (DIO). DIO induces an IL-17B signaling pathway that acts on the cerebral endothelia through IL-17Rb to increase levels of both circulating CXCL5 and local endothelial expression of CXCL5 in both the DIO mouse model and in humans with imaging or pathologic evidence of cerebral small vessel disease. In the white matter, endothelial CXCL5 acts as a chemoattractant and promotes the association of oligodendrocyte progenitor cells (OPCs) with cerebral endothelia increasing vessel-associated OPC cell number and triggers OPC gene expression programs regulating migration and chemokine receptor activation. Targeted blockade of IL-17B with peripheral antibody administration reduced the population of vessel-associated OPCs by reducing endothelial CXCL5 expression. CXCL5-mediated sequestration of OPCs to white matter vasculature impairs OPC differentiation after a focal white matter ischemic lesion. DIO promotes a unique white matter endothelial-to-oligodendrocyte progenitor cell signaling pathway that compromises brain repair after stroke.

neuroscience↗

bioRxiv2018

Obesity blocks oligodendrocyte precursor cell differentiation and impedes repair after white matter stroke

Obesity is a growing public health problem that increases rates of white matter atrophy and increases the likelihood of ischemic lesions within white matter. However, the cellular and molecular mechanisms that regulate these changes are unknown. We hypothesized that obesity may alter oligodendrocytes and myelin priming white matter for worsening injury and repair responses after ischemia. C57Bl/6 mice fed a high fat diet (60% kcal from fat) show increased numbers of oligodendrocyte precursor cells (OPCs), decreased myelin thickness with elevated g-ratios, and shorter paranodal axonal segments, indicating accelerated myelin turnover. Fate mapping of OPCs in PDGFR-CreERT;Rpl22tm1.1Psam mice demonstrated that OPC differentiation rates are enhanced by obesity. Gene expression analyses using a novel oligodendrocyte staging assay demonstrated OPC differentiation is blocked by obesity in between the pre-myelinating and myelinating stage. Using a model of subcortical white matter stroke, the number of stroke-responsive OPCs in obese mice was increased after stroke. At early time points after ischemic white matter stroke, spatial mapping of stroke-responsive OPCs indicates that obesity leads to increased OPCs at the edge of ischemic white matter lesions. At later time points, obesity results in increased OPCs within the ischemic lesion while reducing the number of GST-{pi}-positive mature oligodendrocytes in the lesion core. These data indicate that obesity disrupts normal white matter biology by blocking oligodendrocyte differentiation, leads to an exaggerated response of OPCs to white matter ischemia, and limits remyelination after stroke.\n\nSignificance StatementObesity is a growing public health crisis that specifically increases the development of white matter lesions and silent brain infarcts. This relationship implies a direct cellular effect on white matter yet direct evidence is limited. We modeled diet-induced obesity in mice and studied the effect on oligodendrocyte biology and the response to focal white matter stroke. Adult-onset obesity results in thinner myelin, compromised axonal microdomain structure, and blocks the differentiation of OPCs, leaving the white matter with increased numbers of OPCs. After focal white matter stroke in obese mice, the early OPC response to stroke is exaggerated while late reparative OPC differentiation is blocked. These results suggest that obesity specifically blocks OPC differentiation with consequence on brain repair after stroke.

neuroscience↗