Biology subjects

Muhr, J.

Publications and source records attributed to Muhr, J..

5 recordsLinked to original sources

bioRxiv2025

Volatile-Mediated Plant Defense Networks: Field Evidence for Isoprene as a Short-Distance Immune Signal

Isoprene, the most abundant hydrocarbon emitted by vegetation, protects photosynthesis against oxidative and thermal stress and significantly impacts atmospheric chemistry. While laboratory studies suggest a role for isoprene in plant defense, its function in plant-plant communication under natural conditions remains unclear. Here, we demonstrate that isoprene acts as a signaling molecule, triggering systemic immune responses in neighboring plants against bacterial pathogens under field conditions. We established an experimental system using wild-type and transgenic silver birch (Betula pendula) lines engineered to emit varying levels of isoprene. Over two growing seasons, we examined the effects of birch-emitted volatile organic compounds on neighboring Arabidopsis thaliana, including wild-type and immune signaling mutants (llp1: legume lectin-like protein 1; jar1: jasmonate resistant 1). Isoprene emission rates positively correlated with systemic resistance in receiver plants, with higher emissions enhancing inhibition of Pseudomonas syringae growth. This immune response occurred independently of jasmonate signaling but required functional LLP1, suggesting a specific recognition pathway. By combining Arabidopsis mutant responses with birch volatile profiles, we confirmed that isoprene, rather than other terpenoids, mediates this effect. These findings reveal an unrecognized ecological function of isoprene as an airborne immune signal, establishing transgenic birch as a robust model for studying volatile-mediated plant defense networks in natural environments. Our results provide new insights into the molecular mechanisms underlying plant volatile perception and expand our understanding of chemical communication in terrestrial ecosystems. Significance StatementIsoprene, the most abundant volatile organic compound released by plants, protects against abiotic stress. Here, we demonstrate that isoprene also functions under ambient atmosphere as a short-distance immune signal, enhancing neighboring plants resistance to bacterial pathogens. This finding reveals a putative ecological role of isoprene in plant defense networks and suggests strategies for sustainable agriculture and forest management under environmental stress.

plant biology↗

bioRxiv2024

SOX21 suppresses GBM growth by repressing AP-1 regulated target genes

BackgroundTreatment-resistant glioblastoma stem cells (GSCs) drive glioblastoma (GBM) growth and recurrence. Thus, targeting the molecular machinery that sustains GSCs in an undifferentiated and self-renewing state is a promising therapeutic strategy. The transcription factor SOX21 effectively suppresses the tumorigenic capacity of GSCs. However, the mechanism by which SOX21 impedes GSC features is unknown. MethodsPatient-derived GSCs were engineered with a transgenic TetOn system to enable inducible expression of SOX21 or appropriate controls. The capacity of SOX21 to incapacitate GSCs was assessed using in vitro cell culture models and orthotopic mouse models. Cellular and genome-wide techniques, including RNA-seq, ChIP-seq, and ATAC-seq, were employed to examine the mechanisms by which SOX21 regulates GSCs. ResultsWe show that SOX21 expression in primary GSCs induces an anti-tumorigenic transcriptional program, aligning with clinical data showing a positive correlation between SOX21 levels and improved GBM patient survival. Induced SOX21 expression in GSCs within pre-established GBM reduces their capacity to sustain tumor growth and significantly extends the survival of the transplanted mice. Mechanistically, SOX21 functions as a tumor suppressor by binding a large set of AP-1-targeted chromatin regions, leading to epigenetic repression of AP-1-activated genes that support GSC survival and proliferation. Consistently, the anti-tumorigenic activities of SOX21 are replicated by AP-1 inhibitors, while overexpression of the AP-1 family member, c-JUN, counteracts these effects. ConclusionOur findings identify SOX21 as a key regulator that prevents GSC malignancy by targeting and repressing an AP-1-driven, tumor-promoting gene expression program. These results highlight SOX21-regulated pathways as promising therapeutic targets for GBM. Key PointsO_LIInduced SOX21 expression suppresses GSCs and inhibits the growth of established GBM C_LIO_LISOX21 acts as a tumor suppressor in GSCs by directly repressing AP-1-driven genes C_LIO_LIPharmacological inhibition of AP-1 mimics SOX21 activity in GSCs C_LI Importance of the StudyGBM is the most common and aggressive malignant brain tumor in adults. Recurrence following treatment often stems from the failure of therapeutic interventions to effectively target GSCs, which serve as the primary reservoir for tumor regrowth. The resilience of GSCs to treatment is partly due to the inactivation of intrinsic tumor suppressor programs that would otherwise direct GSCs to cellular senescence and death. This study demonstrates that increased expression levels of the tumor suppressor SOX21 in pre-established GBM disrupt tumor progression by disabling self-renewing GSCs. We show that SOX21 exerts its tumor-suppressive function by targeting and repressing an AP-1-driven gene network, which is a key regulator of GSC maintenance and proliferation. By uncovering the molecular mechanisms through which SOX21 controls GSC biology, our findings provide valuable insights for basic cancer research and may inform the development of novel therapeutic strategies for GBM.

cancer biology↗

bioRxiv2023

Dark adaptation is not necessary to drive the proliferative regeneration response in the adult zebrafish retina.

Macular degeneration, retinal detachment, and retinitis pigmentosa are eye diseases which cause damage to the photoreceptors and are considered leading causes of vision loss worldwide (National Eye Institute, 2022). Thus, developing animal models to study processes related to retinal damage, specifically loss of photoreceptors and their pending degeneration/regeneration is critical. This study aims to modify current light-induced retinal degeneration (LIRD) protocols within the zebrafish model to more efficiently replicate the proliferative response that drives regeneration. The most common LIRD model incorporates a 10-14 day dark adaptation period followed by multiple days of constant intense light exposure designed to damage the retinas and induce a proliferation response (Thomas et al., 2012; Vihtelic & Hyde, 2000). Modified procedures have been published and demonstrate that shortened 24-hour dark adaptation periods still result in cellular damage via apoptosis, but the proliferation response (i.e., pending regeneration) was not examined (Khan et al., 2020). Therefore, our study aims to fully eliminate dark adaptation and will use changes in retinal morphology and proliferation as the hallmark of a successfully initiated regeneration response. Dark-adapted (DA-control fish) and non-dark-adapted (NDA-experimental fish) were taken off their housing system and exposed to constant intense light for 24, 36, and 48 hr. to ensure enough time for damage and proliferation to proceed. Retinas were cross-sectioned to include dorsal and ventral retina, immunohistochemically labeled, and the outer nuclear layer (ONL), inner nuclear layer (INL), cones, and proliferation cell nuclear antigen (PCNA)-positive cells were analyzed to determine the level of structural integrity, if cell photoreceptor numbers were altered, and if proliferation occurred in response to light exposure. Dark-adapted (DA) and non-dark-adapted (NDA) zebrafish retinas displayed similar damage and increased proliferation responses to the constant intense light, indicating that the 10-14-day dark adaptation period is not necessary to induce regeneration in adult zebrafish retinas, reducing experimental timing by two weeks.

neuroscience↗

bioRxiv2019

The cold and the drought: effects of extreme weather events on Stem Carbon dynamic in a Mediterranean beech forest

The effects of short-term extreme events on tree functioning and physiology are still rather elusive. European beech is one of the most sensitive species to late frost and water shortage. We investigated the intra-annual C dynamics in stems under such conditions. Wood formation and stem CO2 efflux were monitored in a Mediterranean beech forest for three years (2015-2017), including a late frost (2016) and a summer drought (2017). The late frost reduced radial growth and, consequently, the amount of carbon fixed in the stem biomass by 80%. Stem carbon efflux in 2016 was reduced by 25%, which can be attributed to the reduction of effluxes due to growth respiration. Counter to our expectations, we found no effects of the 2017 summer drought on radial growth and stem carbon efflux. The studied extreme weather events had various effects on tree growth. Even though late spring frost had a devastating impact on beech radial growth in the current year, trees fully recovered in the following growing season, indicating high resilience of beech to this stressful event.

physiology↗

bioRxiv2018

Restriction of chromatin accessibility is necessary for appropriate enhancer expression

Tissue specific gene expression underpins cell type diversity, and arises from the cooperative activities of transcription factors and the chromatin landscape. It has been previously demonstrated that enhancers with specific arrangements of transcription factor binding motifs can bring together commonly and specifically expressed factors in order to stabilize chromatin accessibility and drive spatially restricted reporter expression within different regions of the CNS. However, when reporters were used to analyse the activity of enhancers bound differentially by a common factor in the endoderm and CNS, several examples of non-tissue specific reporter expression were observed. In order to judge whether or not this may have been due to the unregulated chromatin environment of exogenously delivered enhancer reporters, here we have analysed the chromatin landscape of cells from the CNS and endodermal tissues and find that this reflects neighbouring gene expression to a greater degree than transcription factor binding. This work demonstrates that chromatin accessibility plays an essential role in defining enhancer activity in distantly related cell types.

developmental biology↗