Disturbed brain energy metabolism in a rodent model of DYT-TOR1A dystonia.

DYT-TOR1A (DYT1) dystonia, characterized by reduced penetrance and suspected environmental triggers, is explored using a "second hit" DYT-TOR1A rat model. We aim to investigate the biological mechanisms driving the conversion into a dystonic phenotype, focusing on the striatum's role in dystonia pathophysiology. Sciatic nerve crush injury was induced in ∆ETorA rats, lacking spontaneous motor abnormalities, and wild-type (wt) rats. Twelve weeks post-injury, unbiased RNA-sequencing was performed on the striatum to identify differentially expressed genes (DEGs) and pathways. Fenofibrate, a PPARα agonist, was introduced to assess its effects on gene expression. 18F-FDG autoradiography explored metabolic alterations in brain networks. Low transcriptomic variability existed between naïve wt and ∆ETorA rats (17 DEGs). Sciatic nerve injury significantly impacted ∆ETorA rats (1009 DEGs) compared to wt rats (216 DEGs). Pathway analyses revealed disruptions in energy metabolism, specifically in fatty acid ß-oxidation and glucose metabolism. Fenofibrate induced gene expression changes in wt rats but failed in ∆ETorA rats. Fenofibrate increased dystonia-like movements in wt rats but reduced them in ∆ETorA rats. 18F-FDG autoradiography indicated modified glucose metabolism in motor and somatosensory cortices and striatum in both ∆ETorA and wt rats post-injury. Our findings highlight perturbed energy metabolism pathways in DYT-TOR1A dystonia, emphasizing compromised PPARα agonist efficacy in the striatum. Furthermore, we identify impaired glucose metabolism in the brain network, suggesting a potential shift in energy substrate utilization in dystonic DYT-TOR1A rats. These results contribute to understanding the pathophysiology and potential therapeutic targets for DYT-TOR1A dystonia.

Light-sensitive short hypocotyl genes confer symbiotic nodule identity in the legume Medicago truncatula.

Legumes produce specialized root nodules that are distinct from lateral roots in morphology and function, with nodules intracellularly hosting nitrogen-fixing bacteria. We have previously shown that a lateral root program underpins nodule initiation, but there must be additional developmental regulators that confer nodule identity. Here, we show two members of the LIGHT-SENSITIVE SHORT HYPOCOTYL (LSH) transcription factor family, predominantly known to define shoot meristem complexity and organ boundaries, function as regulators of nodule organ identity. In parallel to the root initiation program, LSH1/LSH2 recruit a program into the root cortex that mediates the divergence into nodules, in particular with cell divisions in the mid-cortex. This includes regulation of auxin and cytokinin, promotion of NODULE ROOT1/2 and Nuclear Factor YA1, and suppression of the lateral root program. A principal outcome of LSH1/LSH2 function is the production of cells able to accommodate nitrogen-fixing bacteria, a key feature unique to nodules.

Increase of Body Temperature Immediately After Ovulation in Mares.

To successfully inseminate mares, precise detection of ovulation time is crucial, especially when using frozen-thawed semen. Monitoring body temperature, as has been described in women, could be a noninvasive way to detect ovulation. The objective of this study was to investigate the relationship between the time of ovulation and the variation of body temperature in mares based on automatic continuous measurements during estrus. The experimental group included 21 mares for 70 analyzed estrous cycles. When the mares showed estrous behavior, they were administered intramuscular deslorelin acetate (2.25 mg) in the evening. At the same time, monitoring of body temperature using a sensor device fixed at the left lateral thorax was started and continued for over 60 hours. In 2-hour intervals, transrectal ultrasonography was performed to detect ovulation. Estimated body temperature in the 6 hours following ovulation detection was on average 0.06°C +/- 0.05°C (mean +/- SD) significantly higher when compared with body temperature at the same time on the preceding day (P = .01). In addition, a significant effect of PGF2α administration for estrus induction on the body temperature was found, being significantly higher until 6 hours before ovulation compared to that of uninduced cycles (P = .005). In conclusion, changes in body temperature during estrus in mares were related to ovulation. The increase in body temperature immediately after ovulation might be used in the future to establish automatized and noninvasive systems to detect ovulation. However, the identified temperature rise is relatively small on average and hardly identifiable in the individual mares.

RPG acts as a central determinant for infectosome formation and cellular polarization during intracellular rhizobial infections.

Host-controlled intracellular accommodation of nitrogen-fixing bacteria is essential for the establishment of a functional Root Nodule Symbiosis (RNS). In many host plants, this occurs via transcellular tubular structures (infection threads - ITs) that extend across cell layers via polar tip-growth. Comparative phylogenomic studies have identified RPG (RHIZOBIUM-DIRECTED POLAR GROWTH) among the critical genetic determinants for bacterial infection. In Medicago truncatula, RPG is required for effective IT progression within root hairs but the cellular and molecular function of the encoded protein remains elusive. Here, we show that RPG resides in the protein complex formed by the core endosymbiotic components VAPYRIN (VPY) and LUMPY INFECTION (LIN) required for IT polar growth, co-localizes with both VPY and LIN in IT tip- and perinuclear-associated puncta of M. truncatula root hairs undergoing infection and is necessary for VPY recruitment into these structures. Fluorescence Lifetime Imaging Microscopy (FLIM) of phosphoinositide species during bacterial infection revealed that functional RPG is required to sustain strong membrane polarization at the advancing tip of the IT. In addition, loss of RPG functionality alters the cytoskeleton-mediated connectivity between the IT tip and the nucleus and affects the polar secretion of the cell wall modifying enzyme NODULE PECTATE LYASE (NPL). Our results integrate RPG into a core host machinery required to support symbiont accommodation, suggesting that its occurrence in plant host genomes is essential to co-opt a multimeric protein module committed to endosymbiosis to sustain IT-mediated bacterial infection.

K63-linked ubiquitin chains are a global signal for endocytosis and contribute to selective autophagy in plants.

In contrast to other eukaryotic model organisms, the closely related ubiquitin (Ub)-conjugating enzymes UBC35 and UBC36 are the main sources of K63-linked Ub chains in Arabidopsis.1 Although K63-linked chains have been associated with the regulation of vesicle trafficking, definitive proof for their role in endocytosis was missing. We show that the ubc35 ubc36 mutant has pleiotropic phenotypes related to hormone and immune signaling. Specifically, we reveal that ubc35-1 ubc36-1 plants have altered turnover of integral membrane proteins including FLS2, BRI1, and PIN1 at the plasma membrane. Our data indicates that K63-Ub chains are generally required for endocytic trafficking in plants. In addition, we show that in plants K63-Ub chains are involved in selective autophagy through NBR1, the second major pathway delivering cargoes to the vacuole for degradation. Similar to autophagy-defective mutants, ubc35-1 ubc36-1 plants display an accumulation of autophagy markers. Moreover, autophagy receptor NBR1 interacts with K63-Ub chains, which are required for its delivery to the lytic vacuole.2 Together, we show that K63-Ub chains act as a general signal required for the two main pathways delivering cargo to the vacuole and thus, to maintain proteostasis.

Phytochromes and flowering: legumes do it another way.

Phytochromes have a crucial role in the regulation of flowering in many plants, but the underlying molecular mechanisms vary among species. Recently, Lin et al. described a unique phytochrome A (phyA)-controlled photoperiodic flowering pathway in soybean (Glycine max), revealing a novel mechanism for photoperiodic regulation of flowering.

Tyrosine kinase inhibitors can activate the NLRP3 inflammasome in myeloid cells through lysosomal damage and cell lysis.

Inflammasomes are intracellular protein complexes that promote an inflammatory host defense in response to pathogens and damaged or neoplastic tissues and are implicated in inflammatory disorders and therapeutic-induced toxicity. We investigated the mechanisms of activation for inflammasomes nucleated by NOD-like receptor (NLR) protiens. A screen of a small-molecule library revealed that several tyrosine kinase inhibitors (TKIs)-including those that are clinically approved (such as imatinib and crizotinib) or are in clinical trials (such as masitinib)-activated the NLRP3 inflammasome. Furthermore, imatinib and masitinib caused lysosomal swelling and damage independently of their kinase target, leading to cathepsin-mediated destabilization of myeloid cell membranes and, ultimately, cell lysis that was accompanied by potassium (K+) efflux, which activated NLRP3. This effect was specific to primary myeloid cells (such as peripheral blood mononuclear cells and mouse bone marrow-derived dendritic cells) and did not occur in other primary cell types or various cell lines. TKI-induced lytic cell death and NLRP3 activation, but not lysosomal damage, were prevented by stabilizing cell membranes. Our findings reveal a potential immunological off-target of some TKIs that may contribute to their clinical efficacy or to their adverse effects.

Transcellular progression of infection threads in Medicago truncatula roots is associated with locally confined cell wall modifications.

The root nodule symbiosis with its global impact on nitrogen fertilization of soils is characterized by an intracellular colonization of legume roots by rhizobia. Although the symbionts are initially taken up by morphologically adapted root hairs, rhizobia persistently progress within a membrane-confined infection thread through several root cortical and later nodular cell layers. Throughout this transcellular passaging, rhizobia have to repeatedly pass host plasma membranes and cell walls. Here, we investigated this essential process and describe the concerted action of one of the symbiosis-specific pectin methyl esterases (SyPME1) and the nodulation pectate lyase (NPL) at the infection thread and transcellular passage sites. Their coordinated function mediates spatially confined pectin alterations in the cell-cell interface that result in the establishment of an apoplastic compartment where bacteria are temporarily released into and taken up from the subjacent cell. This process allows successful intracellular progression of infection threads through the entire root cortical tissue.

Stabilization of membrane topologies by proteinaceous remorin scaffolds.

In plants, the topological organization of membranes has mainly been attributed to the cell wall and the cytoskeleton. Additionally, few proteins, such as plant-specific remorins have been shown to function as protein and lipid organizers. Root nodule symbiosis requires continuous membrane re-arrangements, with bacteria being finally released from infection threads into membrane-confined symbiosomes. We found that mutations in the symbiosis-specific SYMREM1 gene result in highly disorganized perimicrobial membranes. AlphaFold modelling and biochemical analyses reveal that SYMREM1 oligomerizes into antiparallel dimers and may form a higher-order membrane scaffolding structure. This was experimentally confirmed when expressing this and other remorins in wall-less protoplasts is sufficient where they significantly alter and stabilize de novo membrane topologies ranging from membrane blebs to long membrane tubes with a central actin filament. Reciprocally, mechanically induced membrane indentations were equally stabilized by SYMREM1. Taken together we describe a plant-specific mechanism that allows the stabilization of large-scale membrane conformations independent of the cell wall.

Exchange of a Tracheal Tube and Supraglottic Airway Device: Evaluation of Different Techniques in Three Simulated Airway Scenarios (TUBE Study)-A Prospective, Randomised Controlled Study.

BACKGROUND: The swapping of a supraglottic airway device or a tracheal tube in anaesthetised adult patients is a challenging procedure because potential complications through hypoxemia and loss of airway may occur, with life-threatening implications. This study aims to evaluate which airway technique offers the highest success rate concerning a secure airway in established supraglottic airway and tracheal tube airway exchange scenarios. METHODS: After ethical approval, anaesthesiologists were randomised 1:1 into simulated scenarios: an LTS group (malpositioned laryngeal tube) and a Cuff group (relevant cuff leakage of a placed tracheal tube). After that, both groups completed a common scenario consisting of a partially obstructed tracheal tube lumen in a fixed prone position with a Mayfield clamp. The primary endpoint was a successful tracheal airway exchange within ten minutes after the start of the scenario and before severe hypoxemia (SpO2 < 80%) arose. Secondary endpoints were the evaluation of factors influencing success after 10 min. RESULTS: In total, 60 anaesthesiologists (LTS group n = 30; Cuff group n = 30) with a median experience of 7 years (IQR 4-11) were observed. Within 10 min, a malpositioned laryngeal tube was successfully exchanged by 27/30 (90%) participants, compared to the exchange of a tracheal tube with a relevant cuff leakage by 29/30 (97%; p > 0.05). An airway exchange in an obstructed tube scenario occurred in 22/59 (37%). Loss of airway maintenance showed an obvious association with failure in the common scenario (p = 0.02). CONCLUSION: The results of this simulation-based study reflect that the exchange of an existing but insufficient airway device in clinical practice is a high-risk procedure. Especially in a fixed prone position, the deliberate evaluation of the existing airway patency and well-conceived airway management in the case of the accidental loss of the airway or obstructed airway access are crucial.

The B-type response regulator GmRR11d mediates systemic inhibition of symbiotic nodulation.

Key to the success of legumes is the ability to form and maintain optimal symbiotic nodules that enable them to balance the trade-off between symbiosis and plant growth. Cytokinin is essential for homeostatic regulation of nodulation, but the mechanism remains incompletely understood. Here, we show that a B-type response regulator GmRR11d mediates systemic inhibition of nodulation. GmRR11d is induced by rhizobia and low level cytokinin, and GmRR11d can suppress the transcriptional activity of GmNSP1 on GmNIN1a to inhibit soybean nodulation. GmRR11d positively regulates cytokinin response and its binding on the GmNIN1a promoter is enhanced by cytokinin. Intriguingly, rhizobial induction of GmRR11d and its function are dependent upon GmNARK that is a CLV1-like receptor kinase and inhibits nodule number in shoots. Thus, GmRR11d governs a transcriptional program associated with nodulation attenuation and cytokinin response activation essential for systemic regulation of nodulation.

Intronic enhancers of the human SNCA gene predominantly regulate its expression in brain in vivo.

Evidence from patients with Parkinson's disease (PD) and our previously reported α-synuclein (SNCA) transgenic rat model support the idea that increased SNCA protein is a substantial risk factor of PD pathogenesis. However, little is known about the transcription control of the human SNCA gene in the brain in vivo. Here, we identified that the DYT6 gene product THAP1 (THAP domain-containing apoptosis-associated protein 1) and its interaction partner CTCF (CCCTC-binding factor) act as transcription regulators of SNCA. THAP1 controls SNCA intronic enhancers' activities, while CTCF regulates its enhancer-promoter loop formation. The SNCA intronic enhancers present neurodevelopment-dependent activities and form enhancer clusters similar to "super-enhancers" in the brain, in which the PD-associated single-nucleotide polymorphisms are enriched. Deletion of the SNCA intronic enhancer clusters prevents the release of paused RNA polymerase II from its promoter and subsequently reduces its expression drastically in the brain, which may provide new therapeutic approaches to prevent its accumulation and thus related neurodegenerative diseases defined as synucleinopathies.

Increase of skin temperature prior to parturition in mares.

Prediction of impending foaling is highly desirable as early intervention may improve mare and foal outcomes. However, monitoring the peripartum mare is a time-consuming challenge for breeders and many foaling prediction systems have limitations. "Heating up" of the mare is empirically used by breeders as a sign of upcoming parturition in mares. The purpose of this study was to investigate if an increase in skin temperature shortly before parturition is detectable and to determine whether such physiological changes could be an additional valuable parameter to predict foaling. For that, 56 foalings of 14 Warmblood mares, 5 Arabian mares, 27 Thoroughbred mares, and 2 mares of other breeds were analyzed in this 2-year-study. Eight mares were monitored in both years. Mares were between 4 and 22 years old (average: 10 ± 5.5 years) and the mean pregnancy length was 342 days (±9 days), resulting in 14 births from primiparous mares and 42 multiparous mares. For monitoring the periparturient mares, the Piavet® system (Piavita AG, Zurich, Switzerland) was fixed daily when the mares had returned from the field between 4:00 and 6:00 p.m. and collected the next morning between 6:30 and 7:30 a.m. until the time of foaling. Nocturnal rhythms of the skin temperature with the highest values at the start of measurements and a nadir at 6:00 a.m. were observed. On the foaling night, we found a rise in skin temperature starting on average around 90 min prepartum. Skin temperatures recorded at 50 min before parturition and at each 5 min time point until rupture of the allantochorion were significantly higher (p < 0.05) than the mean temperatures measured in the 5 nights before parturition at the same time, reaching a difference of approximately 0.5 °C. There was a significant effect of parity (p = 0.04) on skin temperature during the last hours before foaling where primiparous mares showed a higher mean temperature than uni- or pluriparous mares as early as from 180 min on before parturition. In conclusion, our study shows an increase in skin temperature in most mares within 90 min before birth. Using new biomechanical and digital technologies, this finding could generate an additional potential parameter for the detection of impending parturition. However, skin temperature cannot be used as the only predictive diagnostic of impending parturition in the absence of other parameters.

DYT6 mutated THAP1 is a cell type dependent regulator of the SP1 family.

DYT6 dystonia is caused by mutations in the transcription factor THAP1. THAP1 knock-out or knock-in mouse models revealed complex gene expression changes, which are potentially responsible for the pathogenesis of DYT6 dystonia. However, how THAP1 mutations lead to these gene expression alterations and whether the gene expression changes are also reflected in the brain of THAP1 patients are still unclear. In this study we used epigenetic and transcriptomic approaches combined with multiple model systems [THAP1 patients' frontal cortex, THAP1 patients' induced pluripotent stem cell (iPSC)-derived midbrain dopaminergic neurons, THAP1 heterozygous knock-out rat model, and THAP1 heterozygous knock-out SH-SY5Y cell lines] to uncover a novel function of THAP1 and the potential pathogenesis of DYT6 dystonia. We observed that THAP1 targeted only a minority of differentially expressed genes caused by its mutation. THAP1 mutations lead to dysregulation of genes mainly through regulation of SP1 family members, SP1 and SP4, in a cell type dependent manner. Comparing global differentially expressed genes detected in THAP1 patients' iPSC-derived midbrain dopaminergic neurons and THAP1 heterozygous knock-out rat striatum, we observed many common dysregulated genes and 61 of them were involved in dystonic syndrome-related pathways, like synaptic transmission, nervous system development, and locomotor behaviour. Further behavioural and electrophysiological studies confirmed the involvement of these pathways in THAP1 knock-out rats. Taken together, our study characterized the function of THAP1 and contributes to the understanding of the pathogenesis of primary dystonia in humans and rats. As SP1 family members were dysregulated in some neurodegenerative diseases, our data may link THAP1 dystonia to multiple neurological diseases and may thus provide common treatment targets.

Hyaluronic acid plasma levels during high versus low tidal volume ventilation in a porcine sepsis model.

BACKGROUND: Shedding of the endothelial glycocalyx can be observed regularly during sepsis. Moreover, sepsis may be associated with acute respiratory distress syndrome (ARDS), which requires lung protective ventilation with the two cornerstones of application of low tidal volume and positive end-expiratory pressure. This study investigated the effect of a lung protective ventilation on the integrity of the endothelial glycocalyx in comparison to a high tidal volume ventilation mode in a porcine model of sepsis-induced ARDS. METHODS: After approval by the State and Institutional Animal Care Committee, 20 male pigs were anesthetized and received a continuous infusion of lipopolysaccharide to induce septic shock. The animals were randomly assigned to either low tidal volume ventilation, high tidal volume ventilation, or no-LPS-group groups and observed for 6 h. In addition to the gas exchange parameters and hematologic analyses, the serum hyaluronic acid concentrations were determined from central venous blood and from pre- and postpulmonary and pre- and postcerebral circulation. Post-mortem analysis included histopathological evaluation and determination of the pulmonary and cerebral wet-to-dry ratios. RESULTS: Both sepsis groups developed ARDS within 6 h of the experiment and showed significantly increased serum levels of hyaluronic acid in comparison to the no-LPS-group. No significant differences in the hyaluronic acid concentrations were detected before and after pulmonary and cerebral circulation. There was also no significant difference in the serum hyaluronic acid concentrations between the two sepsis groups. Post-mortem analysis showed no significant difference between the two sepsis groups. CONCLUSION: In a porcine model of septic shock and ARDS, the serum hyaluronic acid levels were significantly elevated in both sepsis groups in comparison to the no-LPS-group. Intergroup comparison between lung protective ventilated and high tidal ventilated animals revealed no significant differences in the serum hyaluronic acid levels.

Current practice of German anesthesiologists in airway management : Results of a national online survey.

BACKGROUND: There is a worldwide consensus among experts that guidelines and algorithms on airway management contribute to improved patient safety in anesthesia. The present study aimed to determine the current practice of airway management of German anesthesiologists and assess the safety gap, defined as the difference between observed and recommended practice, amongst these practitioners. OBJECTIVE: To determine the effect of implementing the guidelines on airway management practice in Germany amongst anesthesiologists and identify potential safety gaps. METHODS: A survey was conducted in September 2019 by contacting all registered members of the German Society of Anaesthesiology and Intensive Care Medicine (DGAI) via email. The participants were asked about their personal and institutional background, adherence to recommendations of the current German S1 guidelines and availability of airway devices. RESULTS: A total of 1862 DGAI members completed the questionnaire (response rate 17%). The main outcome was that anesthesiologists mostly adhered to the guidelines, yet certain recommendations, particularly pertaining to specifics of preoxygenation and training, showed a safety gap. More than 90% of participants had a video laryngoscope and half had performed more than 25 awake intubations using a flexible endoscope; however, only 81% had a video laryngoscope with a hyperangulated blade. An estimated 16% of all intubations were performed with a video laryngoscope, and 1 in 4 participants had performed awake intubation with it. Nearly all participants had cared for patients with suspected difficult airways. Half of the participants had already faced a "cannot intubate, cannot oxygenate" (CICO) situation and one in five had to perform an emergency front of neck access (eFONA) at least once. In this case, almost two thirds used puncture-based techniques and one third scalpel-based techniques. CONCLUSION: Current practice of airway management showed overall adherence to the current German guidelines on airway management, yet certain areas need to be improved.

NIN-Like Proteins: Interesting Players in Rhizobia-Induced Nitrate Signaling Response During Interaction with Non-Legume Host Arabidopsis thaliana.

Nitrogen is an essential macronutrient and a key cellular messenger. Plants have evolved refined molecular systems to sense the cellular nitrogen status. This is exemplified by the root nodule symbiosis between legumes and symbiotic rhizobia, where nitrate availability inhibits this mutualistic interaction. Additionally, nitrate also functions as a metabolic messenger, resulting in nitrate signaling cascades which intensively crosstalk with other physiological pathways. Nodule inception-like proteins (NLPs) are key players in nitrate signaling and regulate nitrate-dependent transcription during legume-rhizobia interactions. Nevertheless, the coordinated interplay between nitrate signaling pathways and rhizobacteria-induced responses remains to be elucidated. In our study, we investigated rhizobia-induced changes in the root system architecture of the non-legume host arabidopsis under different nitrate conditions. We demonstrate that rhizobium-induced lateral root growth and increased root hair length and density are regulated by a nitrate-related signaling pathway. Key players in this process are AtNLP4 and AtNLP5, because the corresponding mutants failed to respond to rhizobia. At the cellular level, AtNLP4 and AtNLP5 control a rhizobia-induced decrease in cell elongation rates, while additional cell divisions occurred independently of AtNLP4. In summary, our data suggest that root morphological responses to rhizobia are coordinated by a newly considered nitrate-related NLP pathway that is evolutionarily linked to regulatory circuits described in legumes.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

The plasma membrane-associated Ca2+ -binding protein, PCaP1, is required for oligogalacturonide and flagellin-induced priming and immunity.

Early signalling events in response to elicitation include reversible protein phosphorylation and re-localization of plasma membrane (PM) proteins. Oligogalacturonides (OGs) are a class of damage-associated molecular patterns (DAMPs) that act as endogenous signals to activate the plant immune response. Previous data on early phosphoproteome changes in Arabidopsis thaliana upon OG perception uncovered the immune-related phospho-regulation of several membrane proteins, among which PCaP1, a PM-anchored protein with actin filament-severing activity, was chosen for its potential involvement in OG- and flagellin-triggered responses. Here, we demonstrate that PCaP1 is required for late, but not early, responses induced by OGs and flagellin. Moreover, pcap1 mutants, unlike the wild type, are impaired in the recovery of full responsiveness to a second treatment with OGs performed 24 h after the first one. Localization studies on PCaP1 upon OG treatment in plants expressing a functional PCaP1-GFP fusion under the control of PCaP1 promoter revealed fluorescence on the PM, organized in densely packed punctate structures, previously reported as microdomains. Fluorescence was found to be associated also with endocytic vesicles, the number of which rapidly increased after OG treatment, suggesting both an endocytic turnover of PCaP1 for maintaining its homeostasis at the PM and an OG-induced endocytosis.

Lipid exchanges drove the evolution of mutualism during plant terrestrialization.

Symbiosis with arbuscular mycorrhizal fungi (AMF) improves plant nutrition in most land plants, and its contribution to the colonization of land by plants has been hypothesized. Here, we identify a conserved transcriptomic response to AMF among land plants, including the activation of lipid metabolism. Using gain of function, we show the transfer of lipids from the liverwort Marchantia paleacea to AMF and its direct regulation by the transcription factor WRINKLED (WRI). Arbuscules, the nutrient-exchange structures, were not formed in loss-of-function wri mutants in M. paleacea, leading to aborted mutualism. Our results show the orthology of the symbiotic transfer of lipids across land plants and demonstrate that mutualism with arbuscular mycorrhizal fungi was present in the most recent ancestor of land plants 450 million years ago.