Biology subjects

Suzuki, T.

Publications and source records attributed to Suzuki, T..

At least 55 records · Page 3Linked to original sources

bioRxiv2025

Transcriptomic insights into the tripartite plant-pathogen-mycoparasite interaction reveal novel mechanisms involving fungal secretomes and plant amino acid metabolism

O_LIThe tomato-Cladosporium fulvum (syn. Fulvia fulva) pathosystem has served as a model for the gene-for-gene concept of effectors and resistance proteins, but this binary framework does not include the potential influence of other microbial participants. Here we describe the dramatic changes in gene expression of all members of the tritrophic interaction among tomato, C. fulvum, and mycoparasitic fungus Hansfordia pulvinata. C_LIO_LITranscriptomic analyses of the mycoparasite H. pulvinata during parasitism of C. fulvum on tomato on planta and in vitro revealed a dramatic upregulation of genes encoding small secreted proteins during mycoparasitism, notably, a Nep1-like protein (HpNlp1) lacked typical necrosis-inducing activity but induced the accumulation of antifungal compounds inhibiting spore germination of C. fulvum. C_LIO_LISimilarly, in C. fulvum parasitized by H. pulvinata, effector genes were highly expressed. Strikingly, effector protein Ecp2 was found to share structural similarity with pathogen killer toxin 4 proteins and had broad-spectrum antifungal activity, indicating a dual function in fungal competition and Cf-ECP2-mediated plant resistance. C_LIO_LIIn tomato plants infected by C. fulvum parasitized by H. pulvinata, primary metabolism and defense-related genes were exclusively activated. These results suggest that in the tritrophic interaction, the mycoparasite simultaneously suppressed the pathogen and induced plant resistance. This study uncovers a multilayered molecular network in which the mycoparasite coordinates pathogen suppression and plant defense within the tritrophic interaction. C_LI

microbiology↗

bioRxiv2025

In Vitro Dynamic and Quantitative Monitoring of Strigolactone-signaling Complex Formation by Time-resolved FRET

SummaryStrigolactones (SLs) are a class of plant hormones that play a critical role in the suppression of shoot branching. Furthermore, they are exuded from roots and act as signaling molecules for inter-organism communication in the rhizosphere. Strigolactones trigger those responses by inducing protein-protein interactions (PPIs) of signaling components and subsequent proteolysis of transcriptional repressors. The sequential event involves SL hydrolysis mediated by SL receptors belonging to an /-hydrolase family, although the physiological role of SL hydrolysis is a subject of debate. To date, SL-induced PPIs have been analyzed by methods such as yeast-two hybrid, pull-down, and AlphaScreen assays. However, the kinetic aspect of PPI profiles has not been well studied. Here, we developed an in vitro method to monitor the formation of the SL signaling complex based on Time-Resolved Forster Resonance Energy Transfer (TR-FRET) technology. Our TR-FRET-based assay system allows us to analyze the mode of action of SL analogs from kinetic and quantitative perspectives. Notably, our method revealed differences in the intensity and time-dependency of PPI signals among different SL analogs with a range of hydrolyzabilities. In addition, we found that tolfenamic acid, an antagonist of the SL receptor, inhibited the SL-induced PPI but could not disrupt the already-formed signaling complex. The TR-FRET system was also used to rapidly and specifically detect naturally occurring SLs from root exudates containing many impurities. This work provides insights into the molecular mechanism of SL perception as well as a powerful tool for activity-based screening of SL signaling modulators. Significance statementThe dual roles of strigolactone (SL) receptors in both the perception and deactivation of SLs make it difficult to elucidate the underlying molecular mechanism of SL signaling. We developed a new in vitro method to evaluate the dynamic activation of the SL receptor, and used it to gain deeper insights into the molecular mechanism of SL-signaling complex formation in response to the SL receptor agonists.

plant biology↗

bioRxiv2025

The electrophilic metabolite of kynurenine, kynurenine-CKA, targets C151 in Keap1 to derepress Nrf2.

The Kelch-like ECH-associated protein 1 / Nuclear factor-erythroid 2 p45-related factor 2 (Keap1/Nrf2) system responds to a wide array of structurally diverse small molecules, of both exogenous and endogenous origin, by inducing a robust cytoprotective program that allows adaptation during oxidative, metabolic and inflammatory stress. Here, we report that exposure to the tryptophan metabolite kynurenine and its electrophilic derivative kynurenine-carboxyketoalkene (Kyn-CKA) leads to an increase in the abundance of transcription factor Nrf2 and induction of Nrf2-target genes, including NAD(P)H:quinone oxidoreductase 1 (NQO1), in murine and human cells. Additionally, both kynurenine and Kyn-CKA activate the aryl hydrocarbon receptor (AhR). Using cellular thermal shift assays, we found that Kyn-CKA increases the thermal stability of Keap1-mCherry fusion protein, but not free mCherry, indicating target engagement of Keap1, the principal repressor of Nrf2. The use of purified recombinant BTB domain of Keap1 and its C151S mutant counterpart revealed that Kyn-CKA reacts with wild-type, but not C151S mutant, Keap1-BTB, and at a much faster rate than with the small molecule thiol N-acetyl cysteine, demonstrating Kyn-CKA is targeted to react with C151 by the surrounding protein environment. In close agreement, Kyn-CKA increased the abundance of Nrf2 and expression of NQO1 in mouse embryonic fibroblast (MEF) cells expressing wild-type Keap1, but its inducer potency was greatly diminished in C151S-Keap1 mutant MEFs. Experiments in WT, AhR-knockout, and Nrf2-knockout primary murine bone marrow-derived macrophages showed that Nrf2 is required for the acute anti-inflammatory activity of Kyn-CKA, whereas AhR is dispensable. Together, these findings demonstrate that Kyn-CKA targets C151 in Keap1 to derepress Nrf2 and reveal that Nrf2, but not AhR, is a main contributor to the anti-inflammatory activity of Kyn-CKA in macrophages.

biochemistry↗

bioRxiv2025

Cytoplasmic roles of HSATIII RNAs in RNA granule assembly and production of actin cytoskeleton-associated repeat-containing proteins

HSATIII architectural lncRNAs are nuclear short-tandem repeat ncRNAs induced upon thermal stress and serve as scaffolding molecules for nuclear stress bodies (nSBs), stress-induced membraneless organelles in the nucleus. We report that HSATIII lncRNAs are exported to the cytoplasm during stress recovery, where they form novel cytoplasmic bodies with nucleocytoplasmic RNA-binding proteins, including PURA, PURB, and m6A reader proteins. Recruitment of ALYREF to nSBs promotes HSATIII RNA export. These HSATIII-based granules, named HERALDs (Heat-removal-associated scaffolds), are transported along microtubules and accumulate at distal cellular regions. We further show that cytoplasmic HSATIII RNAs are translated into MEWNG-rich proteins, which interact with actin filaments and form complexes with HSPA8 and stress granule proteins such as ZC3HAV1 and ATXN2L. Together, these findings reveal previously unrecognized cytoplasmic roles of HSATIII RNAs, functioning both as lncRNAs to scaffold RNA granules and as mRNAs to produce proteins during the late phase of thermal stress recovery.

molecular biology↗

bioRxiv2025

Structural basis of lipid-mediated gating in a two-pore domain potassium channel

TOK1 is the first identified member of the K2P channel family and contains additional N- and C-terminal domains, displaying a configuration distinct from that of canonical K2P channels. Although recent advances in structural studies of K2P channels have elucidated their architectures, the structural basis of TOK1 has remained unknown, limiting our understanding of its unique configuration. Here, we present the cryo-electron microscopy (cryo-EM) structure of TOK1, unveiling its distinctive domain architecture. Furthermore, the structures of TOK1 in three distinct states provide mechanistic insights into its regulation through lipid binding and dissociation. Phosphorylation of TOK1 induces the formation of an additional lipid-binding site, leading to channel inactivation. Conversely, upon activation, the phospholipid dissociates, allowing ion permeation. Our comprehensive study, integrating cryo-EM structural analysis, molecular dynamics simulations, electrophysiological recordings, and mass spectrometry, elucidates the distinctive features of TOK1, an atypical K2P channel, and provides a framework for understanding lipid-mediated regulation within this family.

molecular biology↗

bioRxiv2025

MBOAT2 limits the amounts of PUFA in phosphatidylcholine of neonatal and dystrophic skeletal muscle and promotes muscle regeneration

Skeletal muscle regeneration is critically shaped by lipid remodeling, yet regulatory mechanisms involved remain unexplored. We identify MBOAT2, a lysophospholipid acyltransferase highly induced in activated satellite cells, as a key enzyme that limits the amounts of polyunsaturated fatty acids (PUFAs) in phosphatidylcholine (PC). Lipidomic profiling reveals a characteristic PC signature--high in monounsaturated fatty acids (MUFAs) and low in PUFAs--in dystrophic, injured, and neonatal muscle, paralleling elevated Mboat2 expression. Given the susceptibility of PUFAs to oxidative damage and the emerging role of lipid peroxidation in driving muscle atrophy during denervation, disuse, and aging, MBOAT2-mediated enrichment of MUFA-PC may represent a protective and pro-regenerative lipid environment. Loss- and gain-of-function approaches confirm that MBOAT2 remodels PC and promotes myogenic repair. Our findings uncover a lipid remodeling circuit in muscle stem cells that buffers oxidative stress and highlight that MBOAT2 may improve regenerative capacity in muscular dystrophy, sarcopenia, and other muscle-wasting conditions. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/686003v1_ufig1.gif" ALT="Figure 1"> View larger version (62K): org.highwire.dtl.DTLVardef@e9acddorg.highwire.dtl.DTLVardef@1541b14org.highwire.dtl.DTLVardef@bdfe54org.highwire.dtl.DTLVardef@1844b89_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2025

Differentially acetylated chitosan oligosaccharides as plant defense elicitors against spider mites

The increasing challenges of pesticide resistance and environmental degradation in modern agriculture require sustainable pest management strategies. This study investigates the efficacy of a specific type of hetero-chitooligosaccharide called DACOS, as a plant defense inducer against the two-spotted spider mite, Tetranychus urticae Koch. DACOS is characterized with 85% deacetylation and an average molecular weight of 1 kDa. In planta bioassays revealed a dose-dependent suppression of mite performance on DACOS-treated leaves of kidney bean seedlings, with peak efficacy occurring at 80 ppm. This concentration reduced mite survival by 30% and fecundity by 59% after six days. In addition to the local effects, mite survival and fecundity were also reduced on untreated leaves of the same seedlings, confirming that the effect of DACOS on plant defense is systemic. Behavioral choice assays revealed that DACOS-treated leaves induced 73% mite repellency. No direct acaricidal effects were observed, which confirms the role of DACOS as a plant defense elicitor. Metabolic profiling revealed enriched pathways (e.g., monoterpenoid biosynthesis and -linolenic acid metabolism) that produce volatile organic compounds with repellent properties. These findings suggest that DACOS is an environmentally friendly biostimulant that can enhance plant defense, bypass pesticide resistance, and promote the sustainability of crop production.

physiology↗

bioRxiv2025

The HDAC2-selective inhibitor KTT-1 attenuates autoimmune arthritis by inhibiting osteoclast differentiation in mice

Histone deacetylases (HDACs) are crucial epigenetic regulators of gene expression through the reversible acetylation of lysine residues, and their inhibition is known to exert anti-arthritic effects. Given the critical role of osteoclasts in bone destruction in rheumatoid arthritis (RA) pathogenesis, targeting HDAC2--whose expression is upregulated during osteoclast differentiation--represents a promising therapeutic strategy. Although the development of highly specific HDAC2 inhibitors has recently attracted considerable attention, no such inhibitor has yet been successfully developed. In the current study, we found that the kinetic-selective HDAC2 inhibitor KTT-1 effectively suppressed arthritis symptoms in the collagen-induced arthritis (CIA) mouse model without causing severe side effects. Furthermore, KTT-1 inhibited osteoclast differentiation at an early stage by downregulating c-Fos expression, suggesting that the KTT-1-mediated anti-arthritis effect was achieved by inhibiting osteoclast differentiation. These findings highlight KTT-1 as a promising therapeutic candidate for the development of targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs).

immunology↗

bioRxiv2025

Wounding activates the HSFA1 transcription factors to promote cellular reprogramming in Arabidopsis

Mechanical injury is a primary trigger for cellular reprogramming during organ regeneration, yet the molecular mechanisms that link wounding to reprogramming remain poorly understood. In this study we identify the Arabidopsis HEAT SHOCK FACTOR A1 (HSFA1) class of transcription factors, being key regulators of the heat stress response, as central players in wound-induced callus formation and shoot regeneration. Loss of HSFA1 function in the hsfa1abd triple mutants severely impairs cellular reprogramming, reducing callus formation from wounded hypocotyls, as well as shoot regeneration from explants. Conversely, overexpression of the HSFA1d gain-of-function variant markedly enhances regeneration. Time-series RNA-seq and ChIP-seq analyses revealed that HSFA1s directly activate the key reprogramming regulators WOUND-INDUCED DEDIFFERENTIATION 1 (WIND1), PLETHORA 3 (PLT3) and ZINC FINGER OF ARABIDOPSIS THALIANA 6 (ZAT6). Furthermore, we demonstrate that HSFA1d activity is attenuated by SIZ1-mediated SUMOylation, linking post-translational modification to the regulation of wound responses. Our findings establish HSFA1s as an early transcriptional hub that integrates wound signals with the activation of a broad gene network that drives cellular reprogramming, thereby providing a mechanistic framework for understanding how stress-responsive transcription factors control regeneration.

plant biology↗

bioRxiv2025

In vitro evaluation of protein-protein interactions in the rice KAI2 ligand signaling complex

KARRIKIN INSENSITIVE 2 (KAI2)/DWARF14-LIKE (D14L) plays key roles in land plant development, environmental responses, and the establishment of arbuscular mycorrhizal symbiosis, likely acting as the receptor for unidentified signaling molecules termed KAI2 ligands (KLs). KL perception by KAI2/D14L promotes DWARF3 (D3)/MORE AXILLARY GROWTH2 (MAX2) F-box protein-mediated ubiquitination of SUPPRESSOR OF MAX2 1 (SMAX1) proteins, thereby transducing the KL signals. Although genetic and in vivo assays have demonstrated the functions of these components, the biochemical details of their interactions remain elusive. Here we investigated physical interactions between rice D14L, D3, and OsSMAX1 in vitro using desmethyl germinone (dMGer), a recently developed KL analog. dMGer elicited KL responses in rice with higher activity and pathway specificity than a widely used KL analog (-)-GR24. dMGer, but not (-)-GR24, directly bound to D14L and promoted the interaction between D14L and D3 in vitro. The interaction between D14L and OsSMAX1 was also enhanced by dMGer. Furthermore, we identified the domain of OsSMAX1 that distinguishes it from its paralog DWARF53 (D53), which is associated with the strigolactone signaling complex. These findings propose a model of the interactions among KL signaling components and highlight the role of the ligand in the signaling complex.

plant biology↗

bioRxiv2025

ibSLS: A Biobank for Democratizing Access to Multi-Omics Data and Biospecimens from Spaceflight Research

During spaceflight, astronauts are exposed to extreme conditions such as microgravity, cosmic radiation, and confinement, which can cause a wide range of health problems. To elucidate the molecular mechanisms underlying these issues and to develop intervention strategies for maintaining physiological homeostasis during space missions, space life science research using mouse models is actively conducted on the International Space Station (ISS). However, because of the high cost and technical complexity of spaceflight experiments, it is critical to maximize the scientific value of each mission by ensuring broad accessibility to both data and biospecimens. To this end, we developed the integrated biobank for Space Life Sciences (ibSLS; https://ibsls.megabank.tohoku.ac.jp), a data-visualization and sample-sharing platform that provides access to transcriptomic and metabolomic datasets generated from JAXAs Mouse Habitat Unit (MHU) missions. The platform features a user-friendly interface, tools for cross-mission analysis, and integration with human multi-omics databases, enabling cross-species comparisons. In addition, ibSLS facilitates biospecimen requests to support downstream research. By promoting open access to spaceflight-derived data and biological resources, ibSLS encourages the participation of researchers from diverse fields in space life science. We believe that ibSLS will make a valuable contribution to both biomedical research on spaceflight-related health issues and the study of diseases on Earth.

bioinformatics↗

bioRxiv2025

An Innate Immune Receptor Toll-1 converts chronic light stress into glial phagocytosis

Chronic stress can cause progressive neuronal degeneration, yet the molecular mechanisms linking stress sensing to neuroimmune responses remain elusive. In this study, using a Drosophila model of chronic light-induced stress, we show that photoreceptor neurons accumulate reactive oxygen species (ROS) and exhibit Toll-1 activation which involves Spatzle ligands and receptor endocytosis. Toll-1 activation in neurons promotes axonal degeneration by inducing expression of the glial phagocytic receptor Draper (Drpr), leading to the engulfment of stressed axons. Genetic interaction analyses indicate that Toll-1 functions upstream of Drpr in a stress-responsive signaling cascade. Blocking either Toll-1 or Drpr attenuates axon loss under light stress, while Toll-1 overexpression exacerbates it. Toll-1 also plays a similar pro-degenerative role in an activity-dependent olfactory neuron degeneration paradigm, pointing to a broader role for this mechanism in neural degeneration. Together, these findings identify a neuron-glia signaling axis that converts sustained stress into structural degeneration.

neuroscience↗

bioRxiv2025

Cytokinin receptor AHK3 modulates root-to-shoot transport of trans-zeatin type cytokinin

Trans-zeatin (tZ)-type cytokinins (CKs) are synthesized in roots in response to nitrate, transported to shoot via xylem, and coordinate diverse physiological processes in aerial organs. Within this mechanism, the regulation of CK biosynthesis by nitrate signaling via NIN-like protein 7 as well as the loading of tZ-type CKs into xylem by ATP-binding cassette transporter G14 have been well studied. However, the roles of other components remain unclear. Here, we show that CK perception and degradation in roots, as mediated by Arabidopsis histidine kinase 3 (AHK3) and CK oxidase/dehydrogenase 4 (CKX4), modulate xylem tZ-type CKs transport and leaf CK status. Grafting experiments demonstrated that root-specific AHK3 deficiency systemically increased leaf blade area through long-distance signals of root-derived tZ-type CK, perceived by shoot-expressed AHK3. Transcriptome and hormonome analyses revealed that root-specific AHK3 deficiency reduced CKX4 expression in roots, elevating tZ-type CK levels in roots and xylem sap and thereby enhancing leaf CK response. Transfer experiments manipulating root nitrate levels showed that root-specific AHK3 deficiency promoted leaf blade area in a manner dependent on both nitrate and root-derived tZ-type CK signaling. Moreover, both nitrate signals and root-expressed AHK3 are required for maximal CKX4 induction in roots, and root-specific CKX4 deficiency enhanced leaf blade area in a nitrate-dependent manner. These findings reveal a novel mechanism in which an AHK3-CKX4 module governs xylem transport of tZ-type CKs, fine-tuning leaf size according to nitrogen availability in roots. SIGNIFICANCE STATEMENTTo clarify a mechanism that attenuates trans-zeatin-type cytokinin transport from roots to shoots in response to nitrate signaling, this study examined the root-specific role of cytokinin receptors. Our results show that cytokinin perception and degradation, as mediated by Arabidopsis histidine kinase 3 and cytokinin oxidase/dehydrogenase 4, modulate xylem trans-zeatin-type cytokinin transport, thereby fine-tuning leaf cytokinin status and growth in a nitrate-dependent manner, providing new insights into long-distance cytokinin transport according to nitrogen availability.

plant biology↗

bioRxiv2025

Lysine lactylation regulates ATF4-mediated stress responses under glucose starvation in canine hemangiosarcoma

Hemangiosarcoma (HSA) is a malignant endothelial tumor that occurs frequently in dogs but is rare in other species including humans. Due to its aggressive behavior and limited therapeutic options, patient prognosis is generally poor. Tumor cells produce excess lactate via anerobic glycolysis, and it regulate gene expressions through histone lactylation in response to cellular metabolic conditions. However, how histone lactylation affects biological behavior under glucose-limited conditions in HSA remains unknown. Here, we established canine HSA cell lines and patient-derived xenograft models and investigated the role of histone lactylation during glucose deprivation. HSA cells exhibited higher global histone lactylation levels than normal endothelial cells. Although glucose restriction reduced global histone lactylation levels, Cleavage Under Targets and Tagmentation (CUT&Tag) analysis revealed enrichment of lactylation peaks at transcription-start sites (TSSs) of ATF4-regulated stress-response, asparagine biosynthesis and immune-related genes. TSSs of stress-response genes were co-occupied with RNA polymerase II phosphorylated at serine 5 and showed increased gene expressions, suggesting that lactylation at TSSs activated transcription under glucose-deprived conditions. [U-13C]glutamine tracing indicated that HSA cells synthesized asparagine from glutamine when glucose was scarce. Asparagine supplementation modestly activated cell proliferation. In HSA patient tissues, H3K18la levels were heterogeneous, and M2-like macrophages preferentially infiltrated tumor regions showing low histone lactylation levels. Consistently, glucose-starved HSA cells attracted macrophages and induced M2-like polarization in vitro. These findings demonstrate that lysine lactylation, possibly histone lactylation, persists even under glucose-deprived conditions and regulate transcription that supports tumor cell survival and fosters a pro-tumor microenvironment. One Sentence SummaryLysine lactylation is enriched at TSSs of stress-response genes under glucose starvation and associated with their transcription in canine hemangiosarcoma.

cancer biology↗

bioRxiv2025

WIND1 controls cell fate transition through histone acetylation and deacetylation during somatic embryogenesis

Regeneration involves large-scale transcriptional reprogramming to drive cell identity transitions. These transcriptional changes are tightly coupled with chromatin remodelling but molecular mechanisms that coordinate these changes remain unclear. Here we show that WOUND INDUCED DEDIFFERENTIATION 1 (WIND1) transcription factor promotes somatic embryogenesis by repressing pre-existing cell fate and activating new cell identity programmes. WIND1 interacts with histone deacetylase HISTONE DEACETYLASE 9 (HDA9) and histone acetyltransferase complex component HOMOLOG OF YEAST ADA1 2a (ADA2a) via conserved N-terminal domain. These interactions enable WIND1 to mediate both H3K27 deacetylation and acetylation at distinct target loci, leading to repression of shoot identity genes such as AINTEGUMENTA (ANT) and activation of embryogenesis regulators including LEAFY COTYLEDON 2 (LEC2). Our findings identify WIND1 as a bifunctional chromatin regulator that integrates opposing histone acetylation dynamics to coordinate transcriptional reprogramming. This mechanism provides a molecular framework for how a transcription factor directs complex cell fate transitions during regeneration

plant biology↗

bioRxiv2025

Cell-Free Protein Crystallization Enables Rapid Structure Determination of Disaccharides and Trisaccharides Using Galectin-10 Crystals

It is critical to understand the conformational selection and dynamics of flexible saccharides via protein-ligand interactions in efforts to elucidate their biofunctional roles. Protein crystals can serve as scaffolds to immobilize small molecules, enabling structural and dynamic analysis of saccharides that are difficult to study by conventional approaches. However, constructing versatile scaffold crystals for high-throughput structural analysis remains challenging because this work involves laborious protein production and crystallization workflows. Here, we report rapid crystallization and structural analysis of saccharide-bound scaffolds by applying cell-free protein crystallization (CFPC) to galectin-10 (Gal-10), a lectin known to crystallize spontaneously in vivo. Using CFPC-generated Gal-10 crystals, we obtained the first atomic-resolution structures of melezitose, one of the trisaccharide, bound to the protein scaffold, revealing binding modes inaccessible by conventional approaches. Normalized B-factor analysis combined with molecular dynamics simulations reveals how the binding-site architecture modulates saccharide flexibility and immobilization. This platform can be extended to other flexible ligands and fragment-based screening.

biophysics↗

bioRxiv2025

Protein kinase C inhibitor suppresses 2-cell stage development and perinuclear vesicle formation in mouse zygotes

Nuclear structure and nucleocytoplasmic interaction are closely linked to the regulation of cellular and higher-order biological processes. An alternative pathway for nucleocytoplasmic transport involving perinuclear vesicle formation and release, termed nuclear envelope budding (NEB), has been observed in diverse species and cell types. NEB-like events have also been reported in mammalian zygotes, including mice. However, their molecular basis remains unclear. Recent results suggest that protein kinase C (PKC) signaling regulates perinuclear vesicle biogenesis during NEB. While multiple PKC isoforms are expressed in mouse oocytes, their functions in zygotes are not fully understood. We investigated the effects of pharmacological PKC inhibition on zygotic development and NEB-like perinuclear vesicle formation. Our results suggest that NEB-like events in mouse zygotes may involve PKC-dependent mechanisms and that PKC activity might be critical for the 1-to 2-cell transition.

developmental biology↗

bioRxiv2025

Reversed functional gradient in primate prefrontal cortex: posterior dominance and frontopolar deactivation

The frontopolar cortex (FPC) is thought to coordinate the more posterior lateral prefrontal cortex (LPFC) during complex, non-routine behaviors through high-level functions such as management of multiple goals, exploration, and self-generated decision-making. However, direct neurophysiological comparisons with other prefrontal regions are lacking, leaving the FPCs putative dominance untested. Contrary to this view, our comparison of neuronal activity across the full anteroposterior LPFC in macaques during six distinct tasks probing these functions revealed a posterior-to-mid LPFC dominance, with resource-allocation, novelty-detection (including reward prediction error), and modality invariant decision-monitoring signals all showing a common posterior bias. In contrast, regardless of task demands, the FPCs strongest encoding was about the most recently executed action, and it displayed minimal object selectivity, even when objects were task-critical. We identified a turning point in this graded posterior-to-anterior transition from task-positive to task-negative regions around the border between the anterior and middle thirds of the LPFC. These findings challenge the prevailing notion that the LPFC is anterior-dominant across primate species, and provide evolutionary constraints on theories of human prefrontal organization.

neuroscience↗