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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2018

Sleep-like bistability, loss of causality and complexity in the brain of Unresponsive Wakefulness Syndrome patients

Unresponsiveness Wakefulness Syndrome (UWS) patients may retain intact portions of the thalamocortical system that are spontaneously active and responsive to sensory stimuli. In these patients, Transcranial Magnetic Stimulation combined with electroencephalography (TMS/EEG) also reveals preserved cortical reactivity, but in most cases, the residual thalamocortical circuits fail to engage complex causal interactions, as assessed by the perturbational complexity index (PCI). Another condition during which thalamocortical circuits are intact, active and reactive, yet unable to generate complex responses, is physiological non-rapid eye movement (NREM) sleep. The underlying mechanism is bistability: the tendency of cortical neurons to fall into a silent period (OFF-period) upon receiving an input. Here we tested whether a pathological form of bistability may be responsible for loss of brain complexity in UWS patients. Time-frequency decomposition analysis of TMS/EEG responses in UWS patients revealed the occurrence of OFF-periods (detected as a transient suppression of high-frequency oscillations in the EEG) similar to the ones evoked by TMS in the cortex of healthy sleeping subjects. Pathological OFF-periods were detected in any cortical area, significantly impaired local causal interactions (as measured by PLF) and prevented the build-up of global complexity (as measured by PCI) in the brain of UWS patients. Our results draw a first link between neuronal events (OFF-periods) and global brain dynamics (complexity) in UWS patients. To the extent that sleep-like bistability represents the common functional endpoint of loss of complexity, detecting its presence and tracking its evolution over time, may offer a valuable read-out to devise, guide and titrate therapeutic strategies aimed at restoring consciousness.

neuroscience↗

bioRxiv2018

An Automated Workflow for Segmenting Single Adult Cardiac Cells from Large-Volume Serial Block-Face Scanning Electron Microscopy Data

This paper presents a new algorithm to automatically segment the myofibrils, mitochondria and nuclei within single adult cardiac cells that are part of a large serial-block-face scanning electron microscopy (SBF-SEM) dataset. The algorithm only requires a set of manually drawn contours that roughly demarcate the cell boundary at routine slice intervals (every 50th, for example). The algorithm correctly classified pixels within the single cell with 97% accuracy when compared to manual segmentations. One entire cell and the partial volumes of two cells were segmented. Analysis of segmentations within these cells showed that myofibrils and mitochondria occupied 47.5% and 51.6% on average respectively, while the nuclei occupy 0.7% of the cell for which the entire volume was captured in the SBF-SEM dataset. Mitochondria clustering increased at the periphery of the nucleus region and branching points of the cardiac cell. The segmentations also showed high area fraction of mitochondria (up to 70% of the 2D image slice) in the sub-sarcolemmal region, whilst it was closer to 50% in the intermyofibrillar space. We finally demonstrate that our segmentations can be turned into 3D finite element meshes for cardiac cell computational physiology studies. We offer our large dataset and MATLAB implementation of the algorithm for research use at www.github.com/CellSMB/sbfsem-cardiac-cell-segmenter/. We anticipate that this timely tool will be of use to cardiac computational and experimental physiologists alike who study cardiac ultrastructure and its role in heart function.

bioengineering↗

bioRxiv2018

The Homeostatic Logic of Reward

Energy homeostasis depends on behavior to predictively regulate metabolic states within narrow bounds. Here we review three theories of homeostatic control and ask how they provide insight into the circuitry underlying energy homeostasis. We offer two contributions. First, we detail how control theory and reinforcement learning are applied to homeostatic control. We show how these schemes rest on implausible assumptions; either via circular definitions, unprincipled drive functions, or by ignoring environmental volatility. We argue active inference can elude these shortcomings while retaining important features of each model. Second, we review the neural basis of energetic control. We focus on a subset of arcuate subpopulations that project directly to, and are thus in a privileged position to opponently modulate, dopaminergic cells as a function of energetic predictions over a spectrum of time horizons. We discuss how this can be interpreted under these theories, and how this can resolve paradoxes that have arisen. We propose this circuit constitutes a homeostatic-reward interface that underwrites the conjoint optimisation of physiological and behavioural homeostasis.

neuroscience↗

bioRxiv2018

Reward signalling in brainstem nuclei under glycemic flux

Phasic dopamine release from mid-brain dopaminergic neurons signals errors of reward prediction (RPE). If reward maximisation is to maintain homeostasis, then the value of primary rewards should be coupled to the homeostatic errors they remediate. This leads to the prediction that RPE signals should be configured as a function of homeostatic state and thus, diminish with the attenuation of homeostatic error. To test this hypothesis, we collected a large volume of functional MRI data from five human volunteers on four separate days. After fasting for 12 hours, subjects consumed preloads that differed in glucose concentration. Participants then underwent a Pavlovian cue-conditioning paradigm in which the colour of a fixation-cross was stochastically associated with the delivery of water or glucose via a gustometer. This design afforded computation of RPE separately for better- and worse-than expected outcomes during ascending and descending trajectories of physiological serum glucose fluctuations. In the parabrachial nuclei, variations in regional activity coding positive RPEs scaled positively with serum glucose for ascending and descending glucose levels. The ventral tegmental area and substantia nigra became more sensitive to negative RPEs when glucose levels were ascending. Together, the results show that RPE signals in key brainstem structures are modulated by homeostatic trajectories of naturally occurring glycemic flux, revealing a tight interplay between homeostatic state and the neural encoding of primary reward in the human brain.

neuroscience↗

bioRxiv2018

Phenotypic convergence in the brain: distinct transcription factors regulate common terminal neuronal characters

Transcription factors regulate the molecular, morphological, and physiological characters of neurons and generate their impressive cell type diversity. To gain insight into general principles that govern how transcription factors regulate cell type diversity, we used large-scale single-cell mRNA sequencing to characterize the extensive cellular diversity in the Drosophila optic lobes. We sequenced 55,000 single optic lobe neurons and glia and assigned them to 52 clusters of transcriptionally distinct single cells. We validated the clustering and annotated many of the clusters using RNA sequencing of characterized FACS-sorted single cell types, as well as marker genes specific to given clusters. To identify transcription factors responsible for inducing specific terminal differentiation features, we used machine-learning to generate a random forest model. The predictive power of the model was confirmed by showing that two transcription factors expressed specifically in cholinergic (apterous) and glutamatergic (traffic-jam) neurons are necessary for the expression of ChAT and VGlut in many, but not all, cholinergic or glutamatergic neurons, respectively. We used a transcriptome-wide approach to show that the same terminal characters, including but not restricted to neurotransmitter identity, can be regulated by different transcription factors in different cell types, arguing for extensive phenotypic convergence. Our data provide a deep understanding of the developmental and functional specification of a complex brain structure.

developmental biology↗

bioRxiv2018

GSK3 Controls Migration of the Neural Crest Lineage

Migration of the neural crest lineage is critical to its physiological function. Mechanisms controlling neural crest migration are comparatively unknown, due to difficulties accessing this cell population in vivo. Here, we uncover novel requirements of glycogen synthase kinase 3 (GSK3) in regulating the neural crest. We demonstrate that GSK3 is tyrosine phosphorylated (pY) in neural crest cells and that this activation depends on anaplastic lymphoma kinase (ALK), a protein associated with neuroblastoma. Consistent with this, neuroblastoma cells with pathologically increased ALK activity express high levels of pY-GSK3 and migration of these cells can be inhibited by GSK3 or ALK blockade. In normal neural crest cells, loss of GSK3 leads to increased pFAK and misregulation of Rac1 and lamellipodin, key regulators of cell migration. Genetic reduction of GSK-3 results in failure of migration. All together, this work identifies a role for GSK3 in cell migration during neural crest development and cancer.

developmental biology↗

bioRxiv2018

Methionine metabolism influences the genomic architecture of H3K4me3 with the link to gene expression encoded in peak width

Nutrition and metabolism are known to influence chromatin biology and epigenetics by modifying the levels of post-translational modifications on histones, yet how changes in nutrient availability influence specific aspects of genomic architecture and connect to gene expression is unknown. To investigate this question we considered, as a model, the metabolically-driven dynamics of H3K4me3, a histone methylation mark that is known to encode information about active transcription, cell identity, and tumor suppression. We analyzed the genome-wide changes in H3K4me3 and gene expression in response to alterations in methionine availability under conditions that are known to affect the global levels of histone methylation in both normal rodent physiology and in human cancer cells. Surprisingly, we found that the location of H3K4me3 peaks at specific genomic loci was largely preserved under conditions of methionine restriction. However, upon examining different geometrical features of peak shape, it was found that the response of H3K4me3 peak width encoded almost all aspects of H3K4me3 biology including changes in expression levels, and the presence of cell identity and cancer associated genes. These findings reveal simple yet new and profound principles for how nutrient availability modulates specific aspects of chromatin dynamics to mediate key biological features.

genetics↗

bioRxiv2018

A computational framework for converting high-throughput DNA sequencing data into neural circuit connectivity.

There is growing interest in determining the connectivity of neural circuits-the "connectome"-at single neuron resolution. Most approaches to circuit mapping rely on either microscopy or physiology, but these approaches have very limited throughput. We have recently proposed BOINC (Barcoding of Individual Neuronal Connectivity), a radically different approach to connectivity mapping based on high-throughput DNA sequencing. Here we describe the set of computational algorithms that serve to convert sequencing data into neural connectivity. We apply our computational pipeline to the results of proof-of-principle experiments illustrating an implementation of BOINC based on pseudorabies virus (PRV). PRV is capable of traversing individual synapses and carry DNA barcodes from one cell to another. Using this high-throughput sequencing data, we obtain 456-by-486 connectivity matrix between putative neurons. An inexpensive high-throughput technique for establishing circuit connectivity at single neuron resolution would represent a major advance in neuroscience.

neuroscience↗

bioRxiv2018

Functionally asymmetric motor neurons coordinate locomotion of Caenorhabditis elegans

Invertebrate nervous systems are valuable models for fundamental principles of the control of behavior. Ventral nerve cord (VNC) motor neurons in Caenorhabditis elegans represent one of the best studied locomotor circuits, with known connectivity and functional information about most of the involved neuron classes. However, for one of those, the AS motor neurons (AS MNs), no physiological data is available. Combining specific expression and selective illumination, we precisely targeted AS MNs by optogenetics and addressed their role in the locomotion circuit. After photostimulation, AS MNs induce currents in post-synaptic body wall muscles (BWMs), exhibiting an initial asymmetry of excitatory output. This may facilitate complex regulatory motifs for adjusting direction during navigation. By behavioral and photo-inhibition experiments, we show that AS MNs contribute to propagation of the antero-posterior body wave during locomotion. By Ca2+-imaging in AS MNs and in their synaptic partners, we also reveal that AS MNs play a role in mediating forward and backward locomotion by integrating activity of premotor interneurons (PINs), as well as in coordination of the dorso-ventral body wave. AS MNs do not exhibit pacemaker properties, but potentially gate VNC central pattern generators (CPGs), as indicated by ceasing of locomotion when AS MNs are hyperpolarized. AS MNs provide positive feedback to the PIN AVA via gap junctions, a feature found also in other locomotion circuits. In sum, AS MNs have essential roles in coordinating locomotion, combining several functions, and emphasizing the compressed nature of the C. elegans nervous system in comparison to higher animals.\n\nHighlightsA class of motor neurons with unidentified function - AS cholinergic motor neurons - was characterized in C. elegans.\n\nAS neurons show asymmetry in both input and output and are specialized in coordination of dorso-ventral undulation bends.\n\nAS neurons mediate antero-posterior propagation of the undulatory body wave during locomotion.\n\nAS neurons integrate signals for forward and reverse locomotion from premotor interneurons and may gate ventral nerve cord central pattern generators (CPGs) via gap junctions.

neuroscience↗

bioRxiv2018

Adult Plant Resistance in Maize to Northern Leaf Spot Is a Feature of Partial Loss-of-function Alleles of Hm1

Adult plant resistance (APR) is an enigmatic phenomenon in which resistance genes are ineffective in protecting seedlings from disease but confer robust resistance at maturity. Maize has multiple cases in which genes confer APR to northern leaf spot, a lethal disease caused by Cochliobolus carbonum race 1 (CCR1). The first identified case of APR in maize is encoded by a hypomorphic allele, Hm1A, at the hm1 locus. In contrast, wild type alleles of hm1 provide complete protection at all developmental stages and in every part of the maize plant. Hm1 encodes an NADPH-dependent reductase, which inactivates HC-toxin, a key virulence effector of CCR1. Cloning and characterization of Hm1A ruled out differential transcription or translation for its APR phenotype and identified an amino acid substitution that reduced HC-toxin reductase (HCTR) activity. The possibility of a causal relationship between the weak nature of Hm1A and its APR phenotype was confirmed by the generation of two new APR alleles of Hm1 by mutagenesis. The HCTRs encoded by these new APR alleles had undergone relatively conservative missense changes that partially reduced their enzymatic activity similar to HM1A. No difference in accumulation of HCTR was observed between adult and juvenile plants, suggesting that the susceptibility of seedlings derives from a greater need for HCTR activity, not reduced accumulation of the gene product. Conditions and treatments that altered the photosynthetic output of the host had a dramatic effect on resistance imparted by the APR alleles, demonstrating a link between the energetic or metabolic status of the host and disease resistance affected by HC-toxin catabolism by the APR alleles of HCTR.\n\nAUTHOR SUMMARYAdult plant resistance (APR) is a phenomenon in which disease resistance genes are able to confer resistance at the adult stages of the plant but somehow fail to do so at the seedling stages. Despite the widespread occurrence of APR in various plant diseases, the mechanism underlying this trait remains obscure. It is not due to the differential transcription of these genes, and here we show that it is also not due to the differential translation or activity of the APR alleles of the maize hm1 gene at different stages of development. Using a combination of molecular genetics, biochemistry and physiology, we present multiple lines of evidence that demonstrate that APR is a feature or symptom of weak forms of resistance. While the mature parts of the plant are metabolically robust enough to manifest resistance, seedling tissues are not, leaving them vulnerable to disease. Growth conditions that compromise the photosynthetic output of the plant further deteriorate the ability of the seedlings to protect themselves from pathogens.\n\nOne sentence summaryCharacterization of adult plant resistance in the maize-CCR1 pathosystem reveals a causal link between weak resistance and APR.

pathology↗

bioRxiv2018

HOTAIR primes the Ewing sarcoma family of tumors for tumorigenesis via epigenetic dysregulation involving LSD1

The EWS-FLI1 fusion protein drives oncogenesis in the Ewing sarcoma family of tumors (ESFT) in humans, but its toxicity in normal cells requires additional cellular events for oncogenesis. We show that the lncRNA HOTAIR maintains cell viability in the presence of EWS-FLI1 and redirects epigenetic regulation in ESFT. HOTAIR is consistently overexpressed in ESFTs and is not driven by EWS-FLI1. Repression of HOTAIR in ESFT cell lines significantly reduces anchorage-independent colony formation in vitro and impairs tumor xenograft growth in vivo. Overexpression of HOTAIR in human mesenchymal stem cells (hMSCs), a putative cell of origin of ESFT, and IMR90 cells induces colony formation. Critically, HOTAIR-expressing hMSCs and IMR90 cells remain viable with subsequent EWS-FLI1 expression. HOTAIR induces histone modifications and gene repression through interaction with the epigenetic modifier LSD1 in ESFT cell lines and hTERT-hMSCs. Our findings suggest that HOTAIR maintains ESFT viability through epigenetic dysregulation.\n\nSignificanceWhile the EWS-FLI1 fusion gene was determined to be the oncogenic driver in the overwhelming majority of ESFT, it is toxic to cell physiology and requires one or more additional molecular events to maintain cell viability. As these tumors have surprisingly few genetic mutations at diagnosis, epigenetic changes have been considered to be such an event, but the mechanism by which these changes are driven remains unclear. Our work shows that HOTAIR is consistently expressed among ESFT and induces epigenetic and gene expression changes that cooperate in tumorigenesis. Furthermore, expression of HOTAIR allows for cell viability in the setting of subsequent EWS-FLI1 expression. Our findings elucidate new steps of malignant transformation in this cancer and identify novel therapeutic targets.

cancer biology↗

bioRxiv2018

Building superfast muscles: insights from molecular parallelism in fast-twitch muscle proteins in echolocating mammals

Detecting associations between genomic changes and phenotypic differences is fundamental to understanding how phenotypes evolved. By systematically screening for parallel amino acid substitutions, we detected known as well as novel cases (Strc, Tecta, Cabp2) of parallelism between echolocating bats and toothed whales in proteins that could contribute to high frequency hearing adaptations. Interestingly, our screen also showed that echolocating mammals exhibit an unusually high number of parallel substitutions in fast-twitch muscle fiber proteins. Both bats and dolphins produce an extremely rapid call rate when homing in on their prey, which was shown in bats to be powered by specialized superfast muscles. We show that these genes with parallel substitutions (Casq1, Atp2a1, Myh2, Myl1) are expressed in the superfast sound-producing muscle of bats. Furthermore, we found that the calcium storage protein calsequestrin 1 of bats and dolphins functionally converged in its ability to form calcium-sequestering polymers at lower calcium concentrations, which may contribute to rapid calcium transients required for superfast muscle physiology. The proteins that our genomic screen detected could be involved in the convergent evolution of vocalization in echolocating mammals by potentially contributing to both rapid Ca2+ transients and increased shortening velocities in superfast muscles.\n\nAbbreviations

evolutionary biology↗

bioRxiv2018

The smallest intestine (TSI) - a low volume in vitro model of the small intestine with increased throughput

AimsTo develop a low volume in vitro model with increased throughput simulating the human small intestine, incorporating the presence of ileal microbiota, to study microbial behaviour in the small intestine.\n\nMethods and ResultsThe Smallest Intestine in vitro model (TSI) was developed. During the simulated passage of the small intestine bile is absorbed by dialysis and pH adjusted to physiologically relevant level. A consortium of seven representative bacterial members of the ileum microbiota is included in the ileal stage of the model. It was found that the model can be applied for the testing of survival of probiotic bacteria in upper intestine. Moreover, it was found, that the presence of the ileal microbiota significantly impacted probiotic survival.\n\nConclusionsTSI allows testing a substantial number of samples, at low cost and short time, and is thus suitable as an in vitro screening platform. Multiples of five reactors can be added to increase the number of biological and technical replicates.\n\nSignificance and Impact of the StudyTSI serves as an alternative for costly and low throughput in vitro models currently existing on the market. Above that, significance of small intestine bacteria presence on survival of probiotic bacteria in the upper intestine was proved.

microbiology↗

bioRxiv2018

PET Brain imaging of α7-nAChR with ASEM Reproducibility, occupancy, receptor density, and changes in schizophrenia

The 7 nicotinic acetylcholine receptor (nAChR) increasingly has been implicated in normal brain physiology, as well as in neuropsychiatric disorders. The a7-nAChR primarily is located in cerebral cortex and sub-cortical regions, compared to the 4{beta}2 nAChR subtype that has a more subcortical distribution. The highly cortical distribution suggests a role of a7-nAChR in cognition. We expanded the first-in-human PET imaging of 7-nAChR with [18F]ASEM from five to 21 healthy non-smoking volunteers and added preliminary evidence of binding in six male patients with schizophrenia. Study aims included 1) confirmation of test-retest reproducibility of [18F]ASEM binding in normal volunteers, 2) demonstration of specificity of [18F]ASEM binding by competition with DMXB-A, an 7-nAChR partial agonist previously tested in clinical trials of patients with schizophrenia, 3) estimation of [18F]ASEM binding potentials and 7-nAChR density in vivo in humans, and 4) 7-nAChR binding in patients with schizophrenia compared to healthy volunteers.\n\nTest-retest PET confirmed reproducibility (>90%) (variability [≤] 7%) of [18F]ASEM volume of distribution (VO_SCPLOWTC_SCPLOW) estimates in healthy volunteers. Repeated sessions of PET in five healthy subjects included baseline and effect of inhibition after oral administration of 150 mg DMXB-A. From reduction of binding potentials, we estimated the dose-dependent occupancy of 7-nAChR by DMXB-A at 17-49% for plasma concentrations at 60-200 nM DMXB-A. In agreement with evidence post-mortem, 7-nAChR density (Bmax) averaged 0.67-0.82 nM and inhibitor affinity constant (KO_SCPLOWIC_SCPLOW) averaged 170-385 nM. Median VO_SCPLOWTC_SCPLOW in a feasibility study of six patients with schizophrenia was lower than in healthy volunteers in cingulate cortex, frontal cortex, and hippocampus. Mann-Whitney test identified cingulate cortex and hippocampus as regions with significantly lower median VO_SCPLOWTC_SCPLOW in patients than in healthy volunteers when a single outlier patient was excluded from analysis (P = 0.02, corrected for multiple comparisons).

neuroscience↗

bioRxiv2018

Quantum chemistry reveals the thermodynamic principles of redoxbiochemistry

Thermodynamics dictates the structure and function of metabolism. Redox reactions drive cellular energy and material flow. Hence, accurately quantifying the thermodynamics of redox reactions should reveal key design principles that shape cellular metabolism. However, only a limited number of redox potentials have been measured experimentally, and mostly with inconsistent, poorly-reported experimental setups. Here, we develop a quantum chemistry approach for the calculation of redox potentials of biochemical reactions. We demonstrate that our method predicts experimentally measured potentials with unparalleled accuracy. We calculate the reduction potentials of all redox pairs that can be generated from biochemically relevant compounds and highlight fundamental thermodynamic trends that define cellular redox biochemistry. We further use the calculated potentials to address the question of why NAD/NADP are used as the primary cellular electron carriers, demonstrating how their physiological redox range specifically fits the reactions of central metabolism and minimizes the concentration of reactive carbonyls. The use of quantum chemistry tools, as demonstrated in this study, can revolutionize our understanding of key biochemical phenomena by enabling fast and accurate calculation of large datasets of thermodynamic values.

biochemistry↗

bioRxiv2018

Local Protein Dynamics During Microvesicle Exocytosis in Neuroendocrine Cells

Calcium triggered exocytosis is key to many physiological processes, including neurotransmitter and hormone release by neurons and endocrine cells. Dozens of proteins regulate exocytosis, yet the temporal and spatial dynamics of these factors during vesicle fusion remain unclear. Here we use total internal reflection fluorescence microscopy to visualize local protein dynamics at single sites of exocytosis of small synaptic-like microvesicles in live cultured neuroendocrine PC12 cells. We employ two-color imaging to simultaneously observe membrane fusion (using vesicular acetylcholine transporter (VAChT) tagged to pHluorin) and the dynamics of associated proteins at the moments surrounding exocytosis. Our experiments show that many proteins, including the SNAREs syntaxin1 and VAMP2, the SNARE modulator tomosyn, and Rab proteins, are pre-clustered at fusion sites and rapidly lost at fusion. The ATPase NSF is locally recruited at fusion. Interestingly, the endocytic BAR domain-containing proteins amphiphysin1, syndapin2, and endophilins are dynamically recruited to fusion sites, and slow the loss of vesicle membrane-bound cargo from fusion sites. A similar effect on vesicle membrane protein dynamics was seen with the over-expression of the GTPases dynamin1 and dynamin2. These results suggest that proteins involved in classical clathrin-mediated endocytosis can regulate exocytosis of synaptic-like microvesicles. Our findings provide insights into the dynamics, assembly, and mechanistic roles of many key factors of exocytosis and endocytosis at single sites of microvesicle fusion in live cells.

cell biology↗

bioRxiv2018

A master regulatory network restoring brain glutamate homeostasis is coordinately activated in stroke

Post-transcriptional regulation by miRNAs is essential for complex molecular responses to physiological insult and disease. Although many disease-associated miRNAs are known, their global targets and culminating network effects on pathophysiology remain poorly understood. We applied AGO CLIP to systematically elucidate altered miRNA-target interactions in brain following ischemia/reperfusion (I/R) injury. Among 1,190 identified, most prominent was the cumulative loss of target regulation by miR-29 family members. Integration of translational and time-course RNA profiles revealed a dynamic mode of miR-29 target de-regulation, led by acute translational activation and later increase in RNA levels, allowing rapid proteomic changes to take effect. These functional regulatory events rely on canonical and non-canonical miR-29 binding and engage glutamate reuptake signals to control local glutamate levels. These results uncover a miRNA target network that acts acutely to maintain brain homeostasis after ischemic stroke.

neuroscience↗

bioRxiv2018

Arabidopsis HB52 mediates the crosstalk between ethylene and auxin signaling pathways by regulating PIN2, WAG1, and WAG2 during primary root elongation

The gaseous hormone ethylene participates in many physiological processes of plants. It is well known that ethylene-inhibited root elongation involves basipetal auxin delivery requiring PIN2. However, the molecular mechanism how ethylene regulates PIN2 is not well understood. Here, we report that the ethylene-responsive HD-Zip gene HB52 is involved in ethylene-mediated inhibition of primary root elongation. Using biochemical and genetic analyses, we demonstrated that HB52 is ethylene-responsive and acts immediately downstream of EIN3. HB52 knock-down mutants are insensitive to ethylene in primary root elongation while the overexpression lines have dramatically shortened roots like ethylene treated plants. Moreover, HB52 upregulates PIN2, WAG1, and WAG2 by directly binding to their promoter, leading to an enhanced basipetal auxin delivery to the elongation zone and thus inhibiting root growth. Our work uncovers HB52 as an important crosstalk node between ethylene signaling and auxin transport in root elongation.

plant biology↗