Biology subjects

Bhardwaj, S.

Publications and source records attributed to Bhardwaj, S..

16 recordsLinked to original sources

bioRxiv2026

Mechanistic Insights into Unfolding of the Mitochondrial Localization Sequence M1 of TDP-43 and Identification of a MAPKAPK2 Inhibitor as a potential binder of M1 for inhibition of TDP-43's Aberrant Mitochondrial Localization

Mechanistic elucidation and inhibition of the pathogenic aberrant mitochondrial localization of the RNA/DNA-binding protein, TDP-43, can help in the therapeutics of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). A mitochondrial localization sequence of TDP-43, M1, is largely solvent inaccessible, therefore, how it interacts with the mitochondrial import machinery to facilitate TDP-43s transit to mitochondria is unclear. Towards this, we examined the unfolding TDP-43s N-terminal domain (NTD) that hosts M1, using equilibrium all-atom molecular dynamics (MD) simulations, and observed an early loss of the hydrogen-bonded interactions between {beta}4-{beta}5 bridge and the interactions involving residues Phe-35 and Gly-40 of M1, indicating structural lability of M1 to become solvent-accessible that may enhance its interaction with the mitochondrial receptor(s) for import. Furthermore, via virtual screening of 2,115 FDA-approved and 515,545 non-FDA-approved small molecules from ZINC15 database towards binding to M1 and inhibiting TDP-43s mitochondrial import, we identified a molecule, ZINC73240059, that was previously characterized as an inhibitor of MAP kinase-activating protein kinase 2 (MAPKAPK2). ZINC73240059 remains stably bound to M1 of NTD during MD simulations manifesting negative Gibbs free energy ({Delta}G) with significant contribution from Pro-36 of M1. Overall, ZINC73240059 can be a molecule of interest towards thwarting TDP-43s pathogenic mitochondrial localization in ALS.

biophysics↗

bioRxiv2026

Selective Hydrolytic Defluorination of Branched Perfluorooctanoic Acid Isomers by a Haloacid Dehalogenase

Per- and polyfluoroalkyl substances (PFAS) are highly resistant to enzymatic C-F bond cleavage, and hydrolytic defluorination of long-chain PFAS has rarely been demonstrated. Here, we report selective hydrolytic defluorination of branched perfluorooctanoic acid (PFOA) isomers by a haloacid dehalogenase (4A) from Delftia acidovorans strain D4B. A fluoride-specific riboswitch biosensor was used for initial substrate screening, followed by scaled-up assays in which fluoride release was quantified using a fluoride ion-selective electrode. Defluorination products were subsequently identified by liquid chromatography-mass spectrometry (LC-MS). Although purified 4A (10 M) readily catalyzed hydrolytic defluorination of fluoroacetic acid, incubation of PFOA (0.5 mM) with purified 4A resulted in a statistically significant increase in fluoride release at elevated enzyme loading (500 M). High-resolution LC-MS/MS analysis revealed that defluorination products originated from minor branched PFOA isomers rather than linear PFOA. Molecular docking analyses supported catalytically plausible binding geometries for branched PFOA isomers, positioning the substrate -carbon within [~]4 [A] of the catalytic aspartate residue. These findings demonstrate previously unrecognized hydrolytic reactivity of a haloacid dehalogenase toward branched PFAS isomers and expand the known catalytic scope of the haloacid dehalogenase family. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/719434v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@d56316org.highwire.dtl.DTLVardef@15c7961org.highwire.dtl.DTLVardef@24de56org.highwire.dtl.DTLVardef@80f19d_HPS_FORMAT_FIGEXP M_FIG C_FIG SYNOPSISEnzymatic defluorination of PFAS is rarely observed in environmental systems. This study identifies hydrolytic defluorination of branched PFOA isomers, improving understanding of PFAS defluorination at the enzyme level.

synthetic biology↗

bioRxiv2026

Genome wide analysis of YBX1-mediated redistribution of JMJD6 in ER+ breast cancer cells

The molecular mechanisms by which cancer cells proliferate under diminished ER expression leading to intrinsic and acquired resistance to endocrine therapy remain incompletely understood. Here, we identify a previously unrecognized transcriptional axis centred on JMJD6 and YBX1 that cooperatively reprograms chromatin, redistributes enhancer engagement and sustains tumor proliferation when JMJD6 levels are elevated (JOE cells). Through proximity ligation, ChIP-reChIP assays, KO-based ablation experiments, and genome-wide profiling, we demonstrate that YBX1 is required for JMJD6 enrichment at regulatory sites. [~]20% of JMJD6 and YBX1 peaks physically superimpose, and remaining peaks are contained within a neighbourhood of {+/-}50kb. A shared extended binding site (EBS) containing (i) flanking poly-A/poly-T tracts; (ii) a canonical YBX1 recognition sequence; and (iii) a second complementary motif enriched for zinc-finger proteins defines JMJD6-YBX1 regulated enhancers. Histone modification landscapes in JMJD6 overexpressing cells supported the presence of a transcription permissive chromatin. Further, JMJD6/YBX1 siRNA and overexpression analysis in MCF7 cells identified estrogen and interferon gamma signalling as prominent pathways. The most compelling observation was that ER loss was transcriptional in JOE cells and was accompanied by the emergence of JMJD6-YBX1 enhancer sites at alternate genomic positions relative to canonical ER-JMJD6 sites described in estrogen-stimulated cells. These findings offer a mechanistic insight into earlier reports from our group showing that high JMJD6 with YBX1 suppresses ER expression and this could promote endocrine resistance.

cancer biology↗

bioRxiv2025

Pathway Anchored Multimodal Clustering Reveals Circuit Level Signatures in Parkinsons Disease

Parkinsons disease is increasingly understood as a disorder of distributed brain circuits, yet most imaging analyses do not explicitly respect pathway structure. We introduce a pathway-anchored, multimodal clustering framework based on Scalable Robust Variational Compositional Co-clustering (SRVCC) that integrates structural MRI, free-water-corrected diffusion MRI, and DAT-SPECT in anatomically defined circuits. For each pathway, we derive a simple Multimodal Pathway Integrity Score (MPIS) that aggregates z-normalised volume, microstructural, and dopaminergic measures into an interpretable summary of imaging integrity. In the PPMI cohort, SRVCC identifies stable imaging-derived patient clusters and feature modules under explicit model selection and bootstrap/stability checks, with covariate-adjusted analyzes controlling for age, sex, education, and medication. MPIS shows coherent but modest structure-function associations: lower nigrostriatal and frontostriatal integrity relates to higher motor burden (UPDRS-III), while reduced sensory/visuospatial and limbic integrity is linked to lower global cognition (MoCA); microvascular markers robustly stratify imaging profiles but display minimal cross-sectional coupling to these global scales. Feature-level reports highlight dominant region-by-modality contributors (e.g., striatal DAT-SBR, thalamic and cerebellar morphology, white-matter hyperintensity metrics), providing a transparent bridge from multimodal data to circuit-level signatures. This pathway-aware representation offers a principled, reproducible way to summarise multimodal imaging in PD and may support future work on circuit-informed stratification, prognosis, and targeted outcome measures.

neuroscience↗

bioRxiv2025

A combined Eulerian-Lagrangian and thin film approximation model to investigate the disease-specific drug delivery efficacy on realistic lung geometry and breathing profiles

This work presents a computational approach to investigate antiviral aerosol deposition in anatomically realistic human airways under various physiological inhalation conditions. Antiviral drugs are represented as fine liquid droplets that form a thin coating on airway surfaces, primarily targeting early infection sites. The suggested method combines an Eulerian-Lagrangian discrete phase model (DPM) to track droplet motion and an Eulerian wall film (EWF) model to mimic the evolution of deposited liquid films. This combination effectively addresses the shortcomings of previous studies that employed DPM exclusively, which ignored the post-deposition redistribution dynamics of liquid drugs on airway surfaces. Furthermore, the effects of the distressed breathing of patients with chronic obstructive pulmonary disease (COPD) are compared with both idealized and physiologically realistic breathing patterns in healthy individuals. The study assesses airflow parameters, film thickness, deposition efficiency, and surface area coverage for aerosol particles from 1 to 10 {micro}m. Results reveal that distressed breathing patterns of COPD patients significantly alter the deposition preferences between the upper (~5.28%) and lower lobes (~2.52%) compared to the equivalent ideal and realistic healthy inhalations. Moreover, the distressed breathing also limits the drug penetration into deeper generations, as the highest surface coverage is observed at the carinal region rather than the usual left lower lobe (LLL) found in ideal and realistic healthy breathing cases. Such deposition contrasts highlight the importance of optimizing inhalation therapy and device designs for individuals with obstructive airway diseases.

bioengineering↗

bioRxiv2024

JMJD6 and YBX1 physically interact and regulate HOTAIR proximal promoter

In a previous study, we showed JMJD6 interacted with HOTAIR promoter (-123 to -103 bp upstream of TSS, JIR) and augmented its transcription. Maximal JMJD6 mediated induction required (-216 to -123 bp) region. In silico prediction and ENCODE data suggested that YBX1 could be that potential candidate and in this study the region is designated as YBX1 interacting region (YIR). In breast cancer cell lines, we show that JMJD6 and YBX1 regulate each others expression and physically interact with each other when recombinantly expressed, as endogenous proteins and when synthesized in vitro. Domain mapping indicated that A/P domain of YBX1 interacted with JMJC domain of JMJD6. Luciferase activity of HOTAIR promoter constructs, pHP216 and pHP123, increased in presence of YBX1 in MCF7, Vec and JMJD6 overexpressing JOE cells but was lost in the presence of JMJD6 and YBX1 siRNAs. Interestingly, activity of pHP123 that lacks YIR also decreased upon YBX1 knock out (YKO). Next, by individual JMJD6, YBX1 and ChIP-re-ChIP assays we demonstrate that both proteins co-occupy this promoter region. Further, electrophoretic mobility shift assays showed that YIR probes retarded two complexes, which lost intensity in YKO cells. Interestingly, JIR-protein complex disappeared in YKO cells. Together these data imply that YBX1 not only enhanced promoter activity but may also be involved in JMJD6 recruitment. Taken together, our data proposes that the interaction and positive feed forward loop perpetuated by JMJD6 and YBX1 may culminate in HOTAIR induction, which in turn is known to drive tumor progression.

cancer biology↗

bioRxiv2024

Potent and selective repression of SCN9A by engineered zinc finger repressors for the treatment of neuropathic pain

Peripheral neuropathies are estimated to affect several million patients in the US with no long-lasting therapy currently available. In humans, the Nav1.7 sodium channel, encoded by the SCN9A gene, is involved in a spectrum of inherited neuropathies, and has emerged as a promising target for analgesic drug development. The development of a selective Nav1.7 inhibitor has been challenging, in part due to structural similarities among other Nav channels. Here we present preclinical studies for the first genomic medicine approach using engineered zinc finger repressors (ZFRs) specifically targeting human/nonhuman primate (NHP) SCN9A. AAV-mediated delivery of ZFRs in human iPSC-derived neurons resulted in 90% reduction of SCN9A with no detectable off-target activity. To establish proof-of-concept, a ZFR targeting the mouse Scn9a was assessed in the SNI neuropathic pain mouse model, which resulted in up to 70% repression of Scn9a in mouse DRGs and was associated with reduction in pain hypersensitivity as measured by increased mechanical- and cold-induced pain thresholds. AAV-mediated intrathecal delivery of ZFR in NHPs demonstrated up to 60% repression of SCN9A in bulk DRG tissue and on single-cell levels in the nociceptors. The treatment was well tolerated in NHPs, and no dose-limiting findings were observed four weeks after a single intrathecal injection. Taken together, our results demonstrate that AAV-delivered ZFR targeting the SCN9A gene is promising and supports further development as a potential therapy for peripheral neuropathies.

neuroscience↗

bioRxiv2023

ABDS: tool suite for analyzing biologically diverse samples

MotivationAnalytics tools are essential to identify informative molecular features about different phenotypic groups. Among the most fundamental tasks are missing value imputation, signature gene detection, and expression pattern visualization. However, most commonly used analytics tools may be problematic for characterizing biologically diverse samples when either signature genes possess uneven missing rates across different groups yet involving complex missing mechanisms, or multiple biological groups are simultaneously compared and visualized. ResultsWe develop ABDS tool suite tailored specifically to analyzing biologically diverse samples. Mechanism-integrated group-wise imputation is developed to recruit signature genes involving informative missingness, cosine-based one-sample test is extended to detect enumerated signature genes, and unified heatmap is designed to comparably display complex expression patterns. We discuss the methodological principles and demonstrate the conceptual advantages of the three software tools. We also showcase the biomedical applications of these individual tools. Implemented in open-source R scripts, ABDS tool suite complements rather than replaces the existing tools and will allow biologists to more accurately detect interpretable molecular signals among diverse phenotypic samples. Availability and implementationThe R Scripts of ABDS tool suite is freely available at https://github.com/niccolodpdu/ABDS. Contactyuewang@vt.edu Supplementary informationSupplementary materials are available at Bioinformatics Advances online.

bioinformatics↗

bioRxiv2023

Modeling Flow in an In Vitro Anatomical Cerebrovascular Model with Experimental Validation

Acute ischemic stroke (AIS) is a leading cause of mortality that occurs when an embolus becomes lodged in the cerebral vasculature and obstructs blood flow in the brain. The severity of AIS is determined by the location and how extensively emboli become lodged, which are dictated in large part by the cerebral flow and the dynamics of embolus migration which are difficult to measure in vivo in AIS patients. Computational fluid dynamics (CFD) can be used to predict the patient-specific hemodynamics and embolus migration and lodging in the cerebral vasculature to better understand the underlying mechanics of AIS. To be relied upon, however, the computational simulations must be verified and validated. In this study, a realistic in vitro experimental model and a corresponding computational model of the cerebral vasculature are established that can be used to investigate flow and embolus migration and lodging in the brain. First, the in vitro anatomical model is described, including how the flow distribution in the model is tuned to match physiological measurements from the literature. Measurements of pressure and flow rate for both normal and stroke conditions were acquired and corresponding CFD simulations were performed and compared with the experiments to validate the flow predictions. Overall, the CFD simulations were in relatively close agreement with the experiments, to within {+/-}7% of the mean experimental data with many of the CFD predictions within the uncertainty of the experimental measurement. This work provides an in vitro benchmark data set for flow in a realistic cerebrovascular model and is a first step towards validating a computational model of AIS.

bioengineering↗

bioRxiv2022

In vitro-in silico correlation of three-dimensional turbulent flows in an idealized mouth-throat model

There exists an ongoing need to improve the validity and accuracy of computational fluid dynamics (CFD) simulations of turbulent airflows in the extra-thoracic and upper airways. Yet, a knowledge gap remains in providing experimentally-resolved 3D flow benchmarks with sufficient data density and completeness for useful comparison with widely-employed numerical schemes. Motivated by such shortcomings, the present work details to the best of our knowledge the first attempt to deliver in vitro-in silico correlations of 3D respiratory airflows in a generalized mouth-throat model and thereby assess the performance of Large Eddy Simulations (LES) and Reynolds-Averaged Numerical Simulations (RANS). Numerical predictions are compared against 3D volumetric flow measurements using Tomographic Particle Image Velocimetry (TPIV) at three steady inhalation flowrates varying from shallow to deep inhalation conditions. We find that a RANS k-{omega} SST model adequately predicts velocity flow patterns for Reynolds numbers spanning 1500 to 7000, supporting results in close proximity to a more computationally-expensive LES model. Yet, RANS significantly underestimates turbulent kinetic energy (TKE), thus underlining the advantages of LES as a higher-order turbulence modeling scheme. In an effort to bridge future endevours across respiratory research disciplines, we provide end users with the present in vitro -in silico correlation data for improved predictive CFD models towards inhalation therapy and therapeutic or toxic dosimetry endpoints. Author SummaryThe dispersion and ensuing deposition of inhaled airborne particulate matter in the lungs are strongly influenced by the dynamics of turbulent respiratory airflows in the mouth-throat region during inhalation. To cirumvent costly in vitro experimental measurement resources, fluid dynamics (CFD) simulations are widely sought to predict deposition outcomes but often lack detailed experimental data to first validate the three-dimensional (3D) flow structures anticipated to arise in the upper respiratory tract. In an effort to reconcile such data scarcity, we deliver experimental-numerical correlations of 3D respiratory airflows in an idealized 3D printed mouth-throat model against two widely-established numerical schemes with varying computational costs, namely coarse RANS and finer LES technique. Our time-resolved 3D flow data underline the complexity of these physiological inhalation flows, and discuss advantages and drawbacks of the different numerical techniques. With an outlook on future respiratory applications geared towards broad preclinical inhaled aerosol deposition studies, our open source data are made available for future benchmark comparisons for a broad range of end users in the respiratory research community.

bioengineering↗

bioRxiv2022

Single session of rTMS enhances brain metastability and intrinsic ignition

BackgroundEmerging evidence support the view that brain stimulation might improve essential tremor (ET) by altering brain networks and facilitating plasticity. Yet, we are still missing a mechanistic explanation of the whole brain dynamics underlying these plasticity defining changes. MethodIn this study, we explored the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) over left primary motor cortex (L-M1) on functional connectivity dynamics (FCD) in patients with ET. Resting-state fMRI (RsfMRI) was acquired before and after a single session of rTMS in 30 patients with ET and compared with RsfMRI of 20 age and gender matched healthy controls (HCs). We have measured the effect of brain stimulation using network topological re-organization through whole brain integration and segregation, brain stability and capacity of neural propagation through metastability and intrinsic ignition. ResultsPatients with ET had altered FCD measures compared to controls. After a single session rTMS, the brain connectivity measures approached normality and patients with ET revealed significantly higher integration, lower segregation with higher metastability and increased intrinsic ignition. ConclusionBrain metastability and intrinsic ignition measures could be valuable tools in appreciating mechanisms of brain stimulation in ET and other neurological diseases.

neuroscience↗

bioRxiv2021

Dendrite regeneration in C. elegans is controlled by the RAC GTPase CED-10 and the RhoGEF TIAM-1

Neurons are vulnerable to physical insults which compromise the integrity of both dendrites and axons. Although several molecular pathways of axon regeneration are identified, our knowledge of dendrite regeneration is limited. To understand the mechanisms of dendrite regeneration, we used PVD neurons in C. elegans having stereotyped branched dendrites. Using femtosecond laser, we severed the primary dendrites and axon of this neuron. After severing the primary dendrites near the cell body, we observed sprouting of new branches from the proximal site within 6 hours, which regrew further with timein an unstereotyped manner.This was accompanied by reconnection between the proximal and distal dendrites as well as the fusion among the higher-order branches as reported before. We quantified the regeneration pattern in threeaspects -territory length, number of branchesand fusion phenomena.Axonal injury causes a retraction of the severed end followed by a Dual leucine zipper kinase-1 (DLK-1) dependent regrowth from the severed end.We tested the roles of the major axon regenerationsignaling hubs such as DLK-1-RPM-1, cAMP elevation, let-7 miRNA, AKT-1, Phosphatidyl serine exposure/PS in dendrite regeneration. We found that neither regrowth nor fusionis affected by the axon injury pathway molecules. Surprisingly, we found that the RAC GTPase CED-10and its upstream GEF TIAM-1 play a cell-autonomous role in dendrite regeneration. Additionally, function of CED-10 in epidermal cell is critical for post-dendrotomy fusion phenomena. This work describes a novel regulatory mechanism of dendrite regeneration andprovides a framework for understanding the cellular mechanism of dendrite regeneration using PVD neuron as a model system.

neuroscience↗

bioRxiv2021

Ventilation-induced epithelial injury drives biological onset of lung trauma in vitro and is mitigated with anti-inflammatory therapeutics

Mortality rates among patients suffering from acute respiratory failure remain perplexingly high despite maintenance of blood homeostasis. The biotrauma hypothesis advances that mechanical forces from invasive ventilation trigger immunological factors that spread systemically. Yet, how these forces elicit an immune response remains unclear. Here we show that flow-induced stresses under mechanical ventilation can injure the bronchial epithelium of ventilated in vitro upper airway models and directly modulate inflammatory cytokine secretion associated with pulmonary injury. We identify site-specific susceptibility to epithelial erosion in airways from jet-flow impaction and measure an increase in cell apoptosis and modulated secretions of cytokines IL-6, 8 and 10. We find that prophylactic pharmacological treatment with anti-inflammatory therapeutics reduces apoptosis and pro-inflammatory signaling during ventilation. Our 3D in vitro airway platform points to a previously overlooked origin of lung injury and showcases translational opportunities in preclinical pulmonary research towards protective therapies and improved protocols for patient care.

bioengineering↗

bioRxiv2019

Differential regulation of native and learned behavior by creb1/crh-1 in Caenorhabditis elegans

1.Memory formation is crucial for the survival of animals. Here, we study the effect of different crh-1 (C. elegans homolog of mammalian CREB1) mutations on the ability of C. elegans to form long-term memory (LTM). Null mutants in creb1/crh-1 are defective in LTM formation across phyla. We show that specific isoforms of CREB1/CRH-1, CRH-1c and CRH-1e, are primarily responsible for memory related functions of the transcription factor in C. elegans. Silencing of CRH-1e expressing neurons during training for LTM formation abolishes the long-term memory of the animal. Further, CRH-1e expression in RIM or AVE neurons is sufficient to rescue long-term memory defects of creb1/crh-1 null mutants. We show that apart from being LTM defective, creb1/crh-1 null mutant animals show defects in native chemotaxis behavior. We characterize the amino acids K247 and K266 as responsible for the LTM related functions of CRH-1 while being dispensable for its native chemotaxis behavior. These findings provide insight into the spatial and temporal workings of a crucial transcription factor and can be further exploited to find CREB1 targets involved in the process of memory formation.

neuroscience↗

bioRxiv2018

Step-wise evolution of temperature-mediated phenotypic plasticity in eyespot size across nymphalid butterflies

There are two disparate views regarding phenotypic plasticity. One regards plasticity as a derived adaptation to help organisms survive in variable environments1, 2 while the other views plasticity as the outcome of flexible, non-canalized, developmental processes, ancestrally present in most organisms, that helps them colonize or adapt to novel environments3-5 e.g., a pre-adaptation. Both views of plasticity currently lack a rigorous, mechanistic examination of ancestral and derived states and direction of change2. Here we show that the origin of phenotypic plasticity in eyespot size in response to environmental temperature observed in Bicyclus anynana butterflies is a derived adaptation of this lineage. Eyespot size is regulated by temperature-mediated changes in levels of a steroid hormone, 20E, that affects proliferation of eyespot central cells expressing the 20E receptor (EcR)6, 7. By estimating the origin of the known physiological and molecular components of eyespot size plasticity in a comparative framework, we showed that 20E titer plasticity in response to temperature is a pre-adaptation shared by all butterfly species examined, whereas the origin of expression of EcR in eyespot centers, and the origin of eyespot sensitivity to the hormone-receptor complex are both derived traits found only in a subset of species with eyespots. The presence of all three molecular components required to produce a plastic response is only observed in B. anynana. This gradual, step-wise, physiological/molecular response to temperature is a likely adaptation to temperature variation experienced across wet and dry seasons in the habitat of this species. This work supports, thus, the first view of plasticity as a derived adaptation.

evolutionary biology↗

bioRxiv2017

Sex Differences In 20-Hydroxyecdysone Hormone Levels Control Sexual Dimorphism In Bicyclus anynana Butterfly Wing Patterns

In contrast to the important role of hormones in the development of sexual dimorphic traits in vertebrates [1], the differentiation of these traits in insects is attributed exclusively to variation in cell-autonomous mechanisms controlled by members of the sex determination pathway [2], such as doublesex (dsx). Although hormones can shape the development of sexual traits in insects, and interact with dsx to create dimorphisms, variation in hormone levels are not known to cause dimorphism in these traits [3]. Here we show that butterflies use sex-specific differences in 20-hydroxyecdysone (20E) hormone titers to create sexually dimorphic wing ornaments, without the local involvement of dsx. Females of the dry season (DS) form of Bicyclus anynana display a larger sexual ornament on their wings than males, whereas in the wet season (WS) form both sexes have similarly sized ornaments [4]. High levels of circulating 20E during larval development in DS females and WS forms cause proliferation of the cells fated to give rise to this wing ornament, and results in sexual dimorphism in the DS forms. This study advances our understanding of how the environment regulates sex-specific patterns of plasticity of sexual ornaments and conclusively shows that sex-specific variation in hormone titers can play a role in the development of secondary sexual traits in insects, just like they do in vertebrates.\n\nHighlights O_LISex-specific levels of 20E, an insect molting hormone, regulate secondary sexual trait dimorphism and plasticity in butterflies.\nC_LIO_LI20E levels above a threshold promote local patterns of cell division in one sex, but not in the other sex, to create sexually dimorphic eyespots.\nC_LI\n\neTOCSexual selection drives the evolution of ornaments for individuals to display to the opposite sex. Yet, the mechanisms by which sexual selection operates are still not well understood. Here Bhardwaj et al. provide conclusive evidence, for the first time, that male and female insects use variation in levels of hormones to create dimorphism in their sexual ornaments. Authors show that 20-hydroxyecdyone, the insect molting hormone, also functions as a sex hormone in a butterfly. They also show how the environment shapes the development of sexual ornaments at a proximate level.

developmental biology↗