Biology subjects

Larsson, A.

Publications and source records attributed to Larsson, A..

16 recordsLinked to original sources

bioRxiv2026

Biomarker-driven and gene-enhanced viral therapy for malignant peripheral nerve sheath tumor

Background: High-grade malignant peripheral nerve sheath tumors (MPNST) frequently lose Polycomb Repressive Complex 2 (PRC2), reducing the repressive histone mark, H3K27me3. We hypothesized that H3K27me3 loss sensitizes MPNST to oncolytic HSV due to impaired transcriptional resistance. HSV replication is also restricted by the integrated stress response, normally countered by HSV ICP34.5, representing an additional resistance pathway to ICP34.5-attenuated HSV. Methods: PRC2 loss-of-function was evaluated as a biomarker of HSV G47{Delta} ({Delta}ICP34.5) susceptibility in MPNST using isogenic, pharmacologic inhibition, and genetic rescue models. CUT&RUN and RNA-sequencing defined PRC2-dependent viral and host responses. We engineered a G47{Delta}-derived vector (G47{Delta}2) with tumor-regulated ICP34.5 expression [G47{Delta}2,ins(BIRC5>ICP34.5)] and evaluated efficacy in MPNST xenografts. Results: H3K27me3 deficiency increased G47{Delta} sensitivity and viral spread in vitro. CUT&RUN demonstrated PRC2-dependent H3K27me3 accumulation on the viral genome, explaining G47{Delta} activity in H3K27me3-deficient MPNST. RNA sequencing of G47{Delta} infected MPNST cells revealed heightened integrated stress response activity and blunted induction of translation-associated programs in the PRC2-deficient state (both p<0.001), consistent with compensatory resistance at the level of viral protein translation. Accordingly, tumor-regulated ICP34.5 HSV limited daily tumor-volume growth to 0.6% (95% CI, -2.9-4.2%), improving upon both G47{Delta}2 (8.3%; 4.5-12.2%) and controls (22.5%; 17.4-27.8%). A murine gastrointestinal toxicity phenotype reduced all-cause event-free survival, indicating vector and dosing optimizations are needed to widen the therapeutic window. Conclusions: H3K27me3 loss creates a paradoxical antiviral state that tumor-selective ICP34.5 overcomes to rescue HSV anti-tumor activity, supporting biomarker-driven viral engineering to exploit the permissive transcriptional state of H3K27me3-deficient MPNSTs.

cancer biology↗

bioRxiv2025

High-content morphological profiling by Cell Painting in 3D spheroids.

Cell Painting is a popular assay for morphological profiling of multi-labeled 2D monolayer cell cultures used in a wide range of applications. Culturing cells in 3D has potential for higher physiological relevance, such as when studying effects of perturbations. Robust and scalable 3D models can be challenging to characterize through imaging - particularly because light has difficulty penetrating cell multilayers. We introduce a scalable method where the Cell Painting assay is combined with tissue-clearing and applied to 3D spheroids generated in a ULA microplate format. Multi-channel images are acquired using confocal microscopy, and cells can be segmented inside those spheroids allowing for relevant morphological features to be extracted. Our end-to-end analysis pipeline comprises cell segmentation, morphological feature extraction, and between-spheroids and within-spheroid normalization. We demonstrate the method using spheroids cultured from two colorectal cancer cell lines and successfully detect distinct phenotypic changes upon compound treatments, on both spheroid-level using maximum intensity projections and on single cell-level. We show that drugs group by mechanism of action, with biologically relevant clusters especially evident with single-cell data. Finally, we contrast our method to results from 2D Cell Painting and discover a different pattern in DNA damaging drugs in HCT116 colorectal cancer cells. This work lays the foundation for multi-channel image-based screening in 3D spheroids.

pharmacology and toxicology↗

bioRxiv2025

Seven blood biomarkers are associated with TGF-β and VHL-HIF signaling in patients with clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is an aggressive kidney cancer subtype frequently associated with poor prognosis. Most ccRCC cases are asymptomatic in early stages and symptomatic mostly in advanced stages. Furthermore, the heterogeneity of ccRCC presents a challenge to design new treatments. In this study, using proximity extension assay (PEA), we analyzed blood samples from 134 patients with ccRCC and from 111 age- and gender-matched healthy donors. We identified a panel of seven proteins (ANXA1, ESM1, FGFBP1, MDK, METAP2, SDC1, and TFPI2) that are associated with clinicopathological parameters and patient survival. These biomarkers can differentiate patients with ccRCC from the control individuals with high diagnostic sensitivity and specificity. Moreover, by studying protein expression in solid tumors from the same ccRCC patients, we revealed associations between the panel biomarkers and proteins in the TGF-{beta} and VHL-HIF signaling pathways. We found that most tumor promoting biomarkers were positively associated with TGF-{beta} signaling and HIF-2, and negatively associated with pVHL and HIF-1. We also found that most tumor suppressing biomarkers were positively associated with pVHL and HIF-1 and negatively associated with TGF-{beta} signaling and HIF-2. For ccRCC patients, the blood protein biomarkers that were connected to poor prognosis and TGF-{beta}/HIF-2 signaling, as identified in this study, are potentially important assets in personalized medicine.

cancer biology↗

bioRxiv2024

Appropriate glycemic management protects the germline but not uterine environment in type 1 diabetes

Emerging evidence indicates that parental diseases can impact the health of subsequent generations through epigenetic inheritance. Recently, it was shown that maternal diabetes alters the metaphase II oocyte transcriptome, causing metabolic dysfunction in offspring. However, the type 1 diabetes (T1D) mouse models frequently utilized in previous studies may be subject to several confounding factors as a result of severe hyperglycemia. This limits clinical translatability due to improvements in glycemic control for T1D subjects. Therefore, we optimized a T1D mouse model to investigate the effects of appropriately managed maternal glycemic levels on oocytes and intrauterine development. We show that diabetic mice with appropriate glycemic control exhibited better long-term health outcomes, which maintains the oocyte transcriptome and chromatin accessibility. Moreover, we find that human oocytes undergoing in vitro maturation challenged with mildly increased levels of glucose, reflecting appropriate glycemic management, also retained their transcriptome. However, the fetal growth and placental function were still affected despite appropriate glycemic control, underscoring the uterine environment rather than the germline as a pathological factor for developmental programming in appropriately managed diabetes.

developmental biology↗

bioRxiv2023

Fluid restrictive resuscitation with high molecular weight hyaluronan infusion in early peritonitis-sepsis

Sepsis is a condition with high morbidity and mortality. Prompt recognition and initiation of treatment is essential. Despite forming an integral part of sepsis management, fluid resuscitation may also lead to volume overload, which in turn is associated with increased mortality. The optimal fluid strategy in sepsis resuscitation is yet to be defined. Hyaluronan, an endogenous glycosaminoglycan with high affinity to water is an important constituent of the endothelial glycocalyx. We hypothesized that exogenously administered hyaluronan would contribute to endothelial glycocalyx integrity and counteract intravascular volume depletion in a fluid restrictive model of peritonitis. In a prospective, blinded model of porcine peritonitis-sepsis, we randomized animals to intervention with hyaluronan (n=8) or 0.9% saline (n=8). The animals received an infusion of 0.1% hyaluronan 6 ml/kg/h, or the same volume of saline, during the first two hours of peritonitis. Stroke volume variation and hemoconcentration were comparable in the two groups throughout the experiment. Cardiac output (p=0.008 and p=0.017) and diastolic blood pressure (p=0.015 and p=0.019) were higher in the intervention group during the infusion of hyaluronan, but these effects disappeared as the experiment proceeded. The increase in lactate was more pronounced in the intervention group (p=0.041) throughout the experiment, while concentrations of surrogate markers of glycocalyx damage; syndecan 1 (0.6 {+/-} 0.2 ng/ml vs 0.5 {+/-} 0.2 ng/ml, p=0.292), heparan sulphate (1.23 {+/-} 0.2 vs 1.4 {+/-} 0.3 ng/ml, p=0.211) and vascular adhesion protein 1 (7.0 {+/-} 4.1 vs 8.2 {+/-} 2.3 ng/ml, p=0.492) were comparable in the two groups at the end of the experiment. In conclusion, hyaluronan did not counteract intravascular volume depletion in early peritonitis sepsis. The intervention was associated with higher cardiac output and diastolic blood pressure, than placebo, during the infusion. However, the increase in lactate throughout the experiment was more pronounced in the intervention group.

pharmacology and toxicology↗

bioRxiv2022

Loss of RREB1 in pancreatic beta cells reduces cellular insulin content and affects endocrine cell gene expression

Aims/hypothesisGenome-wide studies have uncovered multiple independent signals at the RREB1 locus associated with altered type 2 diabetes risk and related glycemic traits. However, little is known about the function of the zinc finger transcription factor RREB1 in glucose homeostasis or how changes in its expression and/or function influence diabetes risk. MethodsA zebrafish model lacking rreb1a and rreb1b was used to study the effect of RREB1 loss in vivo. Using transcriptomic and cellular phenotyping of a human beta cell model (EndoC-{beta}H1) and human induced pluripotent stem cell (hiPSC)-derived beta-like cells, we investigated how loss of RREB1 expression and activity affects pancreatic endocrine cell development and function. Ex vivo measurements of human islet function were performed in donor islets from carriers of RREB1 T2D-risk alleles. ResultsCRISPR-Cas9-mediated loss of rreb1a and rreb1b function in zebrafish supports an in vivo role for the transcription factor in beta cell mass, beta cell insulin expression, and glucose levels. Loss of RREB1 reduced insulin gene expression and cellular insulin content in EndoC-{beta}H1 cells, and impaired insulin secretion under prolonged stimulation. Transcriptomic analysis of RREB1 knockdown and knockout EndoC-{beta}H1 cells supports RREB1 as a novel regulator of genes involved in insulin secretion. In vitro differentiation of RREB1KO/KO hiPSCs revealed a dysregulation of pro-endocrine cell genes, including RFX family members, suggesting that RREB1 also regulates genes involved in endocrine cell development. Human donor islets from carriers of T2D-risk alleles in RREB1 have altered glucose-stimulated insulin secretion ex vivo, consistent with RREB1 regulating islet cell function. Conclusions/interpretationTogether, our results indicate that RREB1 regulates beta cell function by transcriptionally regulating the expression of genes involved in beta cell development and function. Research in contextO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIHuman genetic variation in RREB1 is associated with altered diabetes risk, variation in glycemic, and anthropometric traits C_LIO_LIRREB1 is a transcription factor that binds to Ras-responsive elements and is expressed in multiple diabetes relevant tissues, including pancreatic islets C_LI What is the key question?O_LIHow does altered expression or function of RREB1 influence diabetes risk? C_LI What are the new findings?O_LIKnockdown and knockout of RREB1 in mature human EndoC-{beta}H1 cells reduces expression of insulin transcript and cellular content, as well as insulin secretion under prolonged stress C_LIO_LICarriers of the T2D-risk RREB1 coding allele trend towards reduced insulin content, but have improved glucose-stimulated insulin secretion C_LIO_LIA loss-of-function zebrafish model suggests that RREB1 is required for insulin expression C_LI How might this impact on clinical practice in the foreseeable future?O_LIRREB1 controls beta cell function and whole-body glucose homeostasis by transcriptionally regulating the development and function of pancreatic beta cells C_LI

physiology↗

bioRxiv2021

Genetic parameters of colostrum and calf serum antibodies in Swedish dairy cattle

BackgroundColostrum with sufficient IgG content is essential for the newborn calf, as it provides passive immunity which substantially affects the probability of survival during rearing. Failure of passive transfer occurs when a calf does not absorb enough antibodies from the colostrum as indicated by less than 10 g/L of IgG in calf serum. Besides delayed access to colostrum, this can be due to low IgG production of the mother or poor IgG absorption by the calf. The aim of this study was to estimate the genetic background of antibody levels and indicator traits for antibodies in colostrum and calf serum, and their correlation with milk production and health. ResultsColostrum data were available from 1340 cows with at least one calving and calf serum data were available from 886 calves from these cows. Antibody concentrations were estimated using refractometry (digital Brix refractometer for colostrum and optical refractometer for serum) as indicator traits and established using ELISAs to determine total IgG and natural antibodies [NAb] of various antibody isotypes in colostrum and serum. Colostrum traits had heritabilities ranging from 0.16 to 0.31 with repeatabilities from 0.21 to 0.55. Brix had positive genetic correlations with all colostrum antibody traits including total IgG (0.68). Calf serum antibody concentrations had heritabilities ranging from 0.25 to 0.59, with a significant maternal effect accounting for 17 to 27% of the variance. When calves later in life produced their first lactation, lactation-average somatic cell score was found to be negatively correlated with NAb in calf serum. ConclusionsOur results suggest that antibody levels in colostrum and calf serum can be increased by means of selection.

genetics↗

bioRxiv2021

High molecular weight hyaluronan - a potential adjuvant to fluid resuscitation in porcine abdominal sepsis

While fluid resuscitation is fundamental in the treatment of sepsis-induced tissue hypo-perfusion, a sustained positive fluid balance is associated with excess mortality. Crystalloids are the mainstay of fluid resuscitation and use of either synthetic colloids or albumin is controversial. Hyaluronan, an endogenous glycosaminoglycan with high affinity to water, has not been tested as adjuvant in fluid resuscitation. We sought to evaluate the effects of hyaluronan as an adjuvant to fluid resuscitation in peritonitis induced sepsis. In a prospective, parallel-grouped, blinded model of porcine peritonitis-sepsis, we randomized animals to intervention with adjuvant hyaluronan (add-on to standard therapy) (n=8) or 0.9% saline (n=8). After the onset of hemodynamic instability the animals received an initial bolus of 0.1 % hyaluronan 1 mg/kg/10 min or placebo (saline) followed by a continuous infusion of 0.1% hyaluronan (1 mg/kg/h) or saline during the experiment. We hypothesized that the administration of hyaluronan would reduce the volume of fluid administered (aiming at stroke volume variation <13%) and/or attenuate the inflammatory reaction. Total volumes of intravenous fluids infused were 17.5 {+/-} 11 ml/kg/h vs. 19.0 {+/-} 7 ml/kg/h in intervention and control groups, respectively (p = 0.442). Plasma IL-6 increased to 2450 (1420 - 6890) pg/ml and 3700 (1410 - 11960) pg/ml (18 hours of resuscitation) in the intervention and control groups (NS). In a post-hoc analysis, modified shock index remained lower in intervention group (p = 0.011 - 0.037). In conclusion adjuvant hyaluronan did not reduce the volume needed for fluid administration or decrease the inflammatory reaction. Adjuvant hyaluronan was, however, associated with lower modified shock index. Bearing in mind that the experiment has a limited group-size we suggest that further studies on hyaluronan in sepsis are warranted.

pharmacology and toxicology↗

bioRxiv2020

Does the Antisecretory Peptide AF-16 modulate fluid balance and inflammation in experimental peritonitis induced sepsis?

Sepsis is a life-threatening condition due to a dysregulated immunological response to infection. Apart from source control and broad-spectrum antibiotics, management is based on fluid resuscitation and vasoactive drugs. Fluid resuscitation implicates the risk of volume overload, which in turn is associated with longer stay in intensive care, prolonged use of mechanical ventilation and increased mortality. Antisecretory factor (AF), an endogenous protein, is detectable in most tissues and in plasma. The biologically active site of the protein is located in an 8-peptide sequence, contained in a synthetic 16-peptide fragment, named AF-16. The protein as well as the peptide AF-16 has multiple modulatory effects on abnormal fluid transport and edema formation/resolution as well as in a variety of inflammatory conditions. Apart from its anti-secretory and anti-inflammatory characteristics, AF is an inhibitor of capillary leakage in intestine. It is not known whether the protein AF or the peptide AF-16 can ameliorate symptoms in sepsis. We hypothesized that AF-16 decreases the degree of hemodynamic instability, the need of fluid resuscitation, vasopressor dose and tissue edema in fecal peritonitis. To test the hypothesis, we induced peritonitis and sepsis by injecting autologous fecal solution into abdominal cavity of anesthetized pigs, and randomized (in a blind manner) the animals to intervention (AF-16, n=8) or control (saline, n=8) group. After onset of hemodynamic instability (defined as mean arterial pressure < 60 mmHg maintained for > 5 minutes), resuscitation was initiated by an infusion of AF-16 or saline. We recorded respiratory and hemodynamic parameters hourly for twenty hours and collected post mortem tissue samples at the end of the experiment. No differences between the groups were observed regarding hemodynamics, fluid balance, lung mechanics, gas exchange or histology. This experimental study suggests that AF-16 does not modulate sepsis symptoms in peritonitis induced sepsis.

pathology↗

bioRxiv2018

Zebrafish larvae as a model system for systematic characterization of drugs and genes in dyslipidemia and atherosclerosis

BackgroundHundreds of loci have been robustly associated with circulating lipids, atherosclerosis and coronary artery disease; but for most loci the causal genes and mechanisms remain uncharacterized.\n\nMethodsWe developed a semi-automated experimental pipeline for systematic, quantitative, large-scale characterization of mechanisms, drugs and genes associated with dyslipidemia and atherosclerosis in a zebrafish model system. We validated our pipeline using a dietary (n>2000), drug treatment (n>1000), and genetic intervention (n=384), and used it to characterize three candidate genes in a GWAS-identified pleiotropic locus on chr 19p13.11 (n>500).\n\nResultsOur results show that five days of overfeeding and cholesterol supplementation had independent pro-atherogenic effects, which could be diminished by concomitant treatment with atorvastatin and ezetimibe. CRISPR-Cas9-induced mutations in orthologues of proof-of-concept genes resulted in higher LDL cholesterol levels (apoea), and more early stage atherosclerosis (apobb.1). Finally, our pipeline helped identify putative causal genes for circulating lipids and early-stage atherosclerosis (LPAR2 and GATAD2A).\n\nConclusionsIn summary, our pipeline facilitates systematic, in vivo characterization of drugs and candidate genes to increase our understanding of disease etiology, and can likely help identify novel targets for therapeutic intervention.

genomics↗

bioRxiv2018

Galaxy-Kubernetes integration: scaling bioinformatics workflows in the cloud

Making reproducible, auditable and scalable data-processing analysis workflows is an important challenge in the field of bioinformatics. Recently, software containers and cloud computing introduced a novel solution to address these challenges. They simplify software installation, management and reproducibility by packaging tools and their dependencies. In this work we implemented a cloud provider agnostic and scalable container orchestration setup for the popular Galaxy workflow environment. This solution enables Galaxy to run on and offload jobs to most cloud providers (e.g. Amazon Web Services, Google Cloud or OpenStack, among others) through the Kubernetes container orchestrator. AvailabilityAll code has been contributed to the Galaxy Project and is available (since Galaxy 17.05) at https://github.com/galaxyproject/ in the galaxy and galaxy-kubernetes repositories. https://public.phenomenal-h2020.eu/ is an example deployment. Suppl. InformationSupplementary Files are available online. Contactpmoreno@ebi.ac.uk, European Molecular Biology Laboratory, EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK, Tel: +44-1223-494267, Fax: +44-1223-484696.

bioinformatics↗

bioRxiv2018

Body composition and growth in full-term small for gestational age and large for gestational age Swedish infants assessed with air displacement plethysmography at birth and at 3-4 months of age.

BackgroundBeing born small for gestational age (SGA) or large for gestational age (LGA) has short and long term metabolic consequences. There is a growing interest in the extent to which body composition, both in the short and the long term, differs in infants born at the extremes of these birth weights.\n\nMethodsBody composition in 25 SGA and 25 LGA infants were assessed during the first days of life and at 3-4 months of age using air displacement plethysmography.\n\nResultsSGA infants had significantly lower body fat (%) at birth compared to LGA infants. SGA infants increased their body weight and length at a significantly higher rate between birth and 3-4 months than LGA infants. Fat mass (g) in SGA infants increased 23 times between birth and 3-4 months of age compared to 2.8 times for LGA infants. At 3-4 months of age LGA infants reached a threshold in body fat (%) while SGA infants were still gaining body fat (%).\n\nConclusionSeveral significant differences have been identified between SGA and LGA infants, indicating that the effects of intrauterine life continues to play an important role in body composition and growth during the first 3-4 months of life.

developmental biology↗

bioRxiv2018

Trans-ethnic genome-wide association study provides insight into effector genes and molecular mechanisms for kidney function and highlights a causal effect on kidney-specific disease aetiologies

Chronic kidney disease (CKD) affects [~]10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assembled genome-wide association studies (GWAS)1-3 of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals from four ancestry groups. We identified 93 loci (20 novel), which were delineated to 127 distinct association signals. These signals were homogenous across ancestries, and were enriched for protein-coding exons, kidney-specific histone modifications, and transcription factor binding sites for HDAC2 and EZH2. Fine-mapping revealed 40 high-confidence variants driving eGFR associations and highlighted potential causal genes with cell-type specific expression in glomerulus, and proximal and distal nephron. Mendelian randomisation (MR) supported causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure (DBP) and hypertension. These results define novel molecular mechanisms and effector genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.

genetics↗

bioRxiv2018

PhenoMeNal: Processing and analysis of Metabolomics data in the Cloud

BackgroundMetabolomics is the comprehensive study of a multitude of small molecules to gain insight into an organisms metabolism. The research field is dynamic and expanding with applications across biomedical, biotechnological and many other applied biological domains. Its computationally-intensive nature has driven requirements for open data formats, data repositories and data analysis tools. However, the rapid progress has resulted in a mosaic of independent - and sometimes incompatible - analysis methods that are difficult to connect into a useful and complete data analysis solution.\n\nFindingsThe PhenoMeNal (Phenome and Metabolome aNalysis) e-infrastructure provides a complete, workflow-oriented, interoperable metabolomics data analysis solution for a modern infrastructure-as-a-service (IaaS) cloud platform. PhenoMeNal seamlessly integrates a wide array of existing open source tools which are tested and packaged as Docker containers through the projects continuous integration process and deployed based on a kubernetes orchestration framework. It also provides a number of standardized, automated and published analysis workflows in the user interfaces Galaxy, Jupyter, Luigi and Pachyderm.\n\nConclusionsPhenoMeNal constitutes a keystone solution in cloud infrastructures available for metabolomics. It provides scientists with a ready-to-use, workflow-driven, reproducible and shareable data analysis platform harmonizing the software installation and configuration through user-friendly web interfaces. The deployed cloud environments can be dynamically scaled to enable large-scale analyses which are interfaced through standard data formats, versioned, and have been tested for reproducibility and interoperability. The flexible implementation of PhenoMeNal allows easy adaptation of the infrastructure to other application areas and omics research domains.

bioinformatics↗

bioRxiv2017

Interoperable and scalable metabolomics data analysis with microservices

Developing a robust and performant data analysis workflow that integrates all necessary components whilst still being able to scale over multiple compute nodes is a challenging task. We introduce a generic method based on the microservice architecture, where software tools are encapsulated as Docker containers that can be connected into scientific workflows and executed in parallel using the Kubernetes container orchestrator. The access point is a virtual research environment which can be launched on-demand on cloud resources and desktop computers. IT-expertise requirements on the user side are kept to a minimum, and established workflows can be re-used effortlessly by any novice user. We validate our method in the field of metabolomics on two mass spectrometry studies, one nuclear magnetic resonance spectroscopy study and one fluxomics study, showing that the method scales dynamically with increasing availability of computational resources. We achieved a complete integration of the major software suites resulting in the first turn-key workflow encompassing all steps for mass-spectrometry-based metabolomics including preprocessing, multivariate statistics, and metabolite identification. Microservices is a generic methodology that can serve any scientific discipline and opens up for new types of large-scale integrative science.

bioinformatics↗

bioRxiv2017

Cell type boundaries organize plant development

In plants the dorsoventral boundary of leaves defines an axis of symmetry through the centre of the organ separating the top (dorsal) and bottom (ventral) tissues. Although the positioning of this boundary is critical for leaf morphogenesis, how the boundary is established and how it influences development remains unclear. Using live-imaging and perturbation experiments we show that leaf orientation, morphology and position are pre-patterned by HD-ZIPIII and KAN gene expression in the shoot, leading to a model in which dorsoventral genes coordinate to regulate plant development by localizing auxin response between their expression domains. However we also find that auxin levels feedback on dorsoventral patterning by spatially organizing HD-ZIPIII and KAN expression in the shoot periphery. By demonstrating that the regulation of these genes by auxin also governs their response to wounds, our results also provide a parsimonious explanation for the influence of wounds on leaf dorsoventrality.\n\nOnce sentence summaryCell type boundaries regulate plant development

developmental biology↗