Biology subjects

Naruse, K.

Publications and source records attributed to Naruse, K..

At least 19 recordsLinked to original sources

bioRxiv2026

A multi-tissue RNA-seq atlas of adult medaka (Oryzias latipes) under salinity and winter-summer sampling contrasts

Medaka (Oryzias latipes) is a euryhaline and eurythermal teleost widely used in genetics and environmental biology. We generated an RNA-sequencing atlas of 11 adult tissues (brain, eye, gill, heart, intestine, kidney, liver, muscle, spleen, ovary, testis) of the strain d-rR/TOKYO, sampled under two independent environmental contrasts: salinity (freshwater versus seawater) and season (winter versus summer). The freshwater and summer groups, reared indoors and outdoors under long days, provide a third contrast between laboratory and outdoor rearing. Typically, one male and one female were sampled per condition, with ten tissues taken from each individual. Ninety libraries were quantified against the medaka RefSeq transcript set (GCF_053564925.1). The resource comprises gene-level TPM and count matrices, differential expression tables for each tissue and contrast, tissue-specificity indices, human ortholog annotations, sample metadata, and a self-contained interactive browser. Because replication is limited and each condition was sampled on its own date, the differential expression tables are intended for hypothesis generation. The dataset supports studies of gene-expression plasticity and comparisons between medaka and humans.

genetics↗

bioRxiv2026

Limitation of External Nutrient Supply Effects by Iron-Driven Internal Phosphorus Cycling in Semi-Enclosed Coastal Waters: A Case Study of Mikawa Bay

The decline in fishery yields in Japan's enclosed coastal seas has been accompanied by a reduction in phytoplankton biomass, suggesting a widespread decrease in ecosystem productivity. Oligotrophication in Mikawa Bay has caused substantial declines in phytoplankton biomass and Manila clam (Ruditapes philippinarum) production. To assess whether external nutrient enhancement could stimulate phytoplankton growth, a controlled demonstration experiment using treated effluent from two sewage treatment plants (WWTPs) was conducted (spanning fiscal years 2022 to 2024) based on analysis using a three-dimensional non-hydrostatic model. Although effluent DIP and nitrogen concentrations were increased, model results showed that WWTP-derived nutrients represent only a minor portion of the total nutrient budget. Field observations revealed limited increases in surface water phosphorus, strong seasonal variability, and only temporary rises in chlorophyll-a and clam harvests. Monthly TP data demonstrated that seasonal DIP pulses, especially spring phosphorus bursts, dominate nutrient dynamics and overshadow external loading effects. Laboratory experiments further showed that phosphate is efficiently fixed by Fe(III) under oxidizing conditions and rapidly released during reductive dissolution of [FeOOH-HPO4]2- complexes, confirming iron as the principal regulator of internal P cycling. Because current numerical models omit iron-driven internal cycling, they cannot accurately predict bioavailable P or ecosystem responses. Overall, the study indicates that localized nutrient enhancement is insufficient to counter long-term oligotrophication, and effective management must integrate nitrogen limitation, internal Fe and P cycling, oceanic exchange, and seasonal variability in Ise and Mikawa Bays.

ecology↗

bioRxiv2026

Oxytocin regulates TN-GnRH3 circuit maturation and mate preference through C1q-dependent synaptic mechanisms

Oxytocin is a key regulator of social behavior, yet how it shapes the neural circuits underlying these behaviors remains unclear. Here, we show that oxytocin signaling is required for the proper maturation of terminal nerve gonadotropin-releasing hormone 3 (TN-GnRH3) circuits that regulate female mate preference in medaka. Disruption of oxytocin signaling reduced expression of the complement component C1q, altered microglial properties, and increased TN-GnRH3 innervation in the optic tectum and dorsolateral telencephalon, suggesting impaired synaptic refinement. In addition, TN-GnRH3 neurons in mutants exhibited disrupted clustering and failed to increase firing frequency in response to visual stimulation, indicating functional deficits. Furthermore, c1qb mutants phenocopied the behavioral and neuronal abnormalities observed in oxytocin signaling-deficient mutants. Together, our findings suggest that oxytocin signaling links microglia-associated synaptic refinement to neural circuit maturation, thereby revealing a previously unrecognized role for oxytocin in shaping social behavior.

neuroscience↗

bioRxiv2026

Heterochrony of axis segmentation underlies extreme morphogenesis in the Japanese eel

Heterochrony is a major mode of vertebrate body plan evolution, yet its molecular and cellular basis remains poorly characterized. Here, we show that axis segmentation in Anguilla japonica--a species that forms 120 vertebrae--is driven by the temporal extension of somitogenesis. This is achieved through the prolonged maintenance of axial progenitors in the tail beyond the hatching stage, coupled to an extreme segment scaling regime that operates under the constraint of minimal axis growth. We identify delayed Hox13 activation and sustained Oct4 expression as molecular signatures of the prolonged segmentation program. Furthermore, we describe two spatially distinct axial progenitor pools that expand stemness in the tail. These findings reveal how the modulation of stemness in time and space drives extreme morphological evolution in vertebrates. One-Sentence SummarySpatiotemporal modulation of stemness drives extreme axis segmentation in the Japanese eel.

developmental biology↗

bioRxiv2025

Empowering medaka fish biology with versatile genomic resources in MedakaBase

Medaka, a group of small, mostly freshwater fishes in the teleost order Beloniformes, includes the rice fish Oryzias latipes, which is a prominent model organism for diverse biological fields. Chromosome-scale genome sequences of the Hd-rR strain of this species were obtained in 2007, and its improved version has facilitated various genome-wide studies. However, despite its widespread utility, omics data for O. latipes are dispersed across various public databases and lack a centralized platform. To address this, the medaka section of the National Bioresource Project (NBRP) of Japan established a genome informatics team in 2022 tasked with providing versatile in silico solutions for bench biologists. This initiative led to the launch of MedakaBase (https://medakabase.nbrp.jp), a web server that enables gene-oriented analysis including exhaustive sequence similarity searches. MedakaBase also provides genome-wide browsing of diverse datasets, including tissue-specific transcriptomes and intraspecific genomic variations, integrated with gene models from different sources. Additionally, the platform offers gene models optimized for single-cell transcriptome analysis, which often requires coverage of the 3' untranslated region (UTR) of transcripts. Currently, MedakaBase provides genome-wide data for seven Oryzias species, including original data for O. mekongensis and O. luzonensis produced by the NBRP team. This article outlines technical details behind the data provided by MedakaBase.

genomics↗

bioRxiv2025

From Red Tides to Healthy Ecosystems by NutrientManagement in Ise Bay and Mikawa Bay

Ise Bay and Mikawa Bay, situated near major urban and industrial areas, have been increasingly affected by water pollution due to human activities. Over time, eutrophication--primarily driven by excess phosphorus (P) and nitrogen (N)--has led to frequent occurrences of red tides and blue tides, significantly impacting coastal fisheries. To mitigate environmental pollution, efforts have focused on purifying the rivers and brackish lakes that flow into these bays. However, as pollution loads have decreased, these bays have transitioned from a eutrophic to an oligotrophic state, leading to a decline in the populations of benthic organisms and their higher consumers. In this study, we examine the relationship between phytoplankton growth--indicated by chlorophyll a (Chl-a)--and nutrient concentrations, particularly P and N. Through this analysis, we determine the optimal levels of P and N necessary to support healthy phytoplankton growth while preventing harmful algal blooms. Based on our findings, we propose a balanced approach to enhancing the nutritional conditions of enclosed coastal waters without triggering red or blue tides.

ecology↗

bioRxiv2025

Discovery and characterisation of gene by environment and epistatic genetic effects in a vertebrate model

Phenotypic variation arises from the interplay between genetic and environmental factors. However, disentangling these interactions for complex traits remains challenging in observational cohorts such as human biobanks. Instead, model organisms where genetic (G) and environmental (E) variation can be controlled offer a valuable complement to human studies in the analysis of higher-order genetic effects such as GxE interactions, dominance, and epistasis. Here, we utilized 76 medaka strains of the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel, to compare heart rate plasticity across temperatures. An F2 segregation analysis identified 16 quantitative trait loci (QTLs), with many exhibiting dominance, GxE, GxG, and GxGxE interactions. We experimentally validated four candidate genes using gene editing, revealing their temperature-sensitive impact on heart function. Finally, we devised simulations to assess how GWAS discovery power is influenced by the choice of statistical models, showing that the apparent additivity in human GWAS is to be expected given study design and sample sizes of current studies. This work demonstrates the value of controlled model organism studies for dissecting the genetics of complex traits and provides guidance on the design of genetic association studies.

genetics↗

bioRxiv2025

Photoperiod decoder 1 regulates seasonal changes in energy metabolism through the growth hormone signaling pathway

Seasonal changes in metabolism are crucial for animals to adapt to annual environmental fluctuations. However, the molecular mechanisms underlying these adaptations remain poorly understood. Here, we identified a novel gene, photoperiod decoder 1 (phod1), which exhibits a unique bimodal expression pattern under long-day conditions in Japanese medaka fish (Oryzias latipes). While phod1 is conserved across many vertebrates, except for eutherians, its function remained unknown. Single-cell RNA sequencing analysis revealed that phod1 is predominantly expressed in specific pituitary cells that co-express opsin and circadian clock genes. Transcriptomic analysis using phod1 knockout fish demonstrated that phod1 is essential for photoperiodic regulation of growth hormone. Furthermore, transcriptomic and metabolomic analyses of the liver, the primary target of growth hormone, revealed significant alterations in energy metabolism. Behavioral analysis also showed that phod1 knockout fish exhibited significantly reduced locomotor activity. These findings indicate that phod1 plays a crucial role in seasonal metabolic adaptation through modulation of the growth hormone signaling pathway.

physiology↗

bioRxiv2024

Nicotine enhances the stemness and tumorigenicity in intestinal stem cells via Hippo-YAP/TAZ and Notch signal pathway

Cigarette smoking is a well-known risk factor inducing the development and progression of various diseases. Nicotine (NIC) is the major constituent of cigarette smoke. However, knowledge of the mechanism underlying the NIC-regulated stem cell functions is limited. In this study, we demonstrate that NIC increases the abundance and proliferative activity of intestinal stem cells (ISCs) in vivo and ex vivo. Moreover, NIC induces Yes-associated protein (YAP) /Transcriptional coactivator with PDZ-binding motif (TAZ) and Notch signaling in ISCs via 7-nicotinic acetylcholine receptor (nAchR) and protein kinase C (PKC) activation; this effect was not detected in Paneth cells. The inhibition of Notch signaling by dibenzazepine (DBZ) nullified the effects of NIC on ISCs. NIC enhances in vivo tumor formation from ISCs after loss of the tumor suppressor gene Apc, DBZ inhibited NIC-induced tumor growth. Hence, this study identifies a NIC-triggered pathway regulating the stemness and tumorigenicity of ISCs and suggests the use of DBZ as a potential therapeutic strategy for treating intestinal tumors.

cell biology↗

bioRxiv2023

Effect of mechanical stretching stimulation on maturation of human iPS cell-derived cardiomyocytes co-cultured with human gingival fibroblasts

In the realm of regenerative medicine, despite the various techniques available for inducing the differentiation of induced pluripotent stem (iPS) cells into cardiomyocytes, there remains a need to enhance the efficiency of this induction process. This study aimed to improve the differentiation efficiency of iPS-derived cardiomyocytes (iPS-CMs) by incorporating mechanical stretching. Human iPS cells were co-cultured with human gingival fibroblasts (HGF) on a polydimethylsiloxane (PDMS) stretch chamber, where mechanical stretching stimulation was applied during the induction of cardiomyocyte differentiation. The maturation of iPS-CMs was assessed using qRT-PCR, immunofluorescence staining, transmission electron microscopy, and contractility comparisons. Results indicated significantly elevated gene expression levels of cardiomyocyte markers (cTnT) and the mesodermal marker (Nkx2.5) in the stretch group compared to the control group. Fluorescent immunocytochemical staining revealed the presence of cardiac marker proteins (cTnT and HCN4) in both groups, with higher protein expression in the stretch group. Additionally, sarcomere length in the stretch group was notably larger than in the control group. A significant increase in the contractility of iPS-CMs was observed in the stretch group. These findings demonstrate that mechanical stretching stimulation enhances the maturity and differentiation efficiency of iPS-CMs co-cultured with fibroblasts.

cell biology↗

bioRxiv2023

Development of a human heart-on-a-chip model using induced pluripotent stem cells, fibroblasts and endothelial cells

In recent years, research on organ-on-a-chip technology has been flourishing, particularly for drug screening and disease model development. Fibroblasts and vascular endothelial cells engage in crosstalk through paracrine signaling and direct cell-cell contact, which is essential for the normal development and function of the heart. Therefore, to faithfully recapitulate cardiac function, it is imperative to incorporate fibroblasts and vascular endothelial cells into a heart-on-a-chip model. Here, we report the development of a human heart-on-a-chip composed of induced pluripotent stem cell (iPSC)-derived cardiomyocytes, fibroblasts, and vascular endothelial cells. Vascular endothelial cells cultured on microfluidic channels responded to the flow of culture medium mimicking blood flow by orienting themselves parallel to the flow direction, akin to in vivo vascular alignment in response to blood flow. Furthermore, the flow of culture medium promoted stronger junction formation between vascular endothelial cells, as evidenced by CD31 staining and lower apparent permeability. The triculture condition of iPSC-derived cardiomyocytes, fibroblasts, and vascular endothelial cells resulted in higher expression of the ventricular cardiomyocyte marker IRX4 and increased contractility compared to the biculture condition with iPSC-derived cardiomyocytes and fibroblasts alone. Such triculture-derived cardiac tissues exhibited cardiac responses similar to in vivo hearts, including an increase in heart rate upon noradrenaline administration. In summary, we have achieved the development of a heart-on-a-chip composed of cardiomyocytes, fibroblasts, and vascular endothelial cells that mimics in vivo cardiac behavior.

cell biology↗

bioRxiv2023

Modular control of time and space during vertebrate axis segmentation

How temporal and spatial control of developmental processes are linked remains a fundamental question. Do underlying mechanisms form a single functional unit or are these dissociable modules? We address this question by studying the periodic process of embryonic axis segmentation, using genetic crosses of inbred medaka fish strains representing two species, Oryzias sakaizumii and latipes. Our analysis revealed correlated interspecies differences with regard to the timing of segmentation, the size of segments and of the presomitic mesoderm (PSM), from which segments are periodically formed. We then did interspecies crosses and real-time imaging quantifications, which revealed extensive phenotypic variation in [~]600 F2 embryos. Importantly, while the F2 analysis showed correlated changes of PSM and segment size, these spatial measures were not correlated to the timing of segmentation. This shows that the control of time and space of axis segmentation can, in principle, be decoupled. In line with this finding, we identified, using developmental quantitative trait loci (devQTL) mapping, distinct chromosomal regions linked to either the control of segmentation timing or PSM size. We were able to validate the devQTL findings using a CRISPR/Cas9 loss-of-function approach on several candidate genes in vivo. Combined, this study reveals that a developmental constraint mechanism underlies spatial scaling of axis segmentation, while its spatial and temporal control are dissociable modules. Our findings emphasise the need to reveal the selective constraints linking these modules in the natural environment.

developmental biology↗

bioRxiv2023

Mechanical signalling via membrane tension drives saltatory neuronal migration

Neurons migrate in a saltatory manner by repeating two distinct steps: extension of the leading process and translocation of the cell body. The former step is critical for determining the migratory route in response to extracellular guidance cues. In the latter step, neurons must generate robust forces that translocate the bulky soma against mechanical barriers of the surrounding three-dimensional environment. However, the link between the leading process extension and subsequent somal translocation remains unknown. By using scanning ion conductance microscopy, we show that leading process extension increases plasma membrane tension. The tension elevation activated mechanosensitive ion channels and triggered Ca2+ influx, leading to actomyosin activation at the rear of the cell. Blockade of this signaling pathway disturbed somal translocation, thereby inhibiting neuronal migration in three-dimensional environments. Thus, mechanical signaling through plasma membrane tension and mechano-channels links the leading process extension to somal translocation, allowing rapid and saltatory neuronal migration.

cell biology↗

bioRxiv2023

Pax3 and Pax7 function in combination with Mitf to generate melanophores and xanthophores in medaka and zebrafish

Neural crest cells generate numerous derivatives, including pigment cells, and are a model for studying how fate specification from multipotent progenitors is controlled. In mammals, the core gene regulatory network (GRN) for melanocytes (their only pigment cell-type) contains three transcription factors Sox10, Pax3 and Mitf, with the latter considered a master regulator of melanocyte development. In teleosts, which have three to four pigment cell types (melanophores, iridophores and xanthophores, plus leucophores e.g. in medaka), GRNs governing fate specification are poorly understood, although Mitf function is considered conserved. Here, we show that the regulatory relationships between Sox10, Pax3 and Mitf are conserved in zebrafish, but the role for Mitf is more complex than previously emphasised, affecting xanthophore development too. Similarly, medaka Mitf is necessary for melanophore, xanthophore and leucophore formation. Furthermore, expression patterns and mutant phenotypes of pax3 and pax7 suggest that Pax3 and Pax7 act sequentially, activating mitf expression. Pax7 modulates Mitf function, driving co-expressing cells to differentiate as xanthophores and leucophores rather than melanophores. We propose that pigment cell fate specification is better considered as resulting from the combinatorial activity of Mitf with other transcription factors.

developmental biology↗

bioRxiv2022

Origin, Prospective Identification, and Function of Circulating Endothelial Colony Forming Cells in Mouse and Human

Most circulating endothelial cells are apoptotic, but rare circulating endothelial colony forming cells (C-ECFCs) with proliferative and vasculogenic activity can be cultured; the origin and naive function of these C-ECFCs remains obscure. Herein, detailed lineage tracing reveals murine C-ECFCs emerge in the early postnatal period, display high vasculogenic potential, with enriched frequency of clonal proliferative cells compared to tissue-resident ECFCs, and are not committed to or derived from the bone marrow hematopoietic system but from tissue-resident ECFCs. In human subjects, C-ECFCs are present in the CD34bright cord blood mononuclear subset, possess proliferative potential and in vivo vasculogenic function in a naive or cultured state, and display a single cell transcriptome sharing some umbilical venous endothelial cell features like, higher Protein C Receptor and extracellular matrix gene expression. This study provides an advance for the field by identifying the origin, naive function, and antigens to prospectively isolate C-ECFCs for translational studies.

cell biology↗

bioRxiv2021

Myosin phosphatase target subunit 1 governs integrity of the embryonic gut epithelium to circumvent atresia development in medaka, Oryzias latipes

Congenital intestinal atresia (IA) is a birth defect characterised by the absence or closure of part of the intestine. Although genetic factors are implicated, mechanistic understanding has been hindered by the lack of suitable animal models. Here, we describe a medaka (Oryzias latipes) mutant, generated by N-ethyl-N-nitrosourea (ENU) mutagenesis, that develops IA during embryogenesis. Positional cloning identified a nonsense mutation in mypt1, encoding myosin phosphatase target subunit 1. Mutant embryos exhibited ectopic accumulation of F-actin and phosphorylated myosin regulatory light chain (Mrlc) in the intestinal epithelium, consistent with disrupted actomyosin regulation. These cytoskeletal abnormalities were accompanied by epithelial disorganisation without notable alterations in cell proliferation, motility, or apoptosis. Inhibition of myh11a, encoding smooth muscle (SM) myosin heavy chain, ameliorated the IA phenotype but Blebbistatin treatment completely rescued the defect, suggesting a non-contractile role prior to SM maturation. Together, these findings demonstrate that mypt1 loss disrupts intestinal morphogenesis through actomyosin dysregulation. Given the recent clinical identification of IA associated with MYPT1 mutations, this medaka model offers a valuable platform to investigate the developmental and molecular basis of MYPT1-associated IA in human.

developmental biology↗

bioRxiv2021

The Medaka Inbred Kiyosu-Karlsruhe (MIKK) Panel

Unraveling the relationship between genetic variation and phenotypic traits remains a fundamental challenge in biology. Mapping variants underlying complex traits while controlling for confounding environmental factors is often problematic. To address this, we have established a vertebrate genetic resource specifically to allow for robust genotype-to-phenotype investigations. The teleost medaka (Oryzias latipes) is an established genetic model system with a long history of genetic research and a high tolerance to inbreeding from the wild. Here we present the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel: the first near-isogenic panel of 80 inbred lines in a vertebrate model derived from a wild founder population. Inbred lines provide fixed genomes that are a prerequisite for the replication of studies, studies which vary both the genetics and environment in a controlled manner and functional testing. The MIKK panel will therefore enable phenotype-to-genotype association studies of complex genetic traits while allowing for careful control of interacting factors, with numerous applications in genetic research, human health, and drug development and fundamental biology. Here we present a detailed characterisation of the genetic variation across the MIKK panel, which provides a rich and unique genetic resource to the community by enabling large-scale experiments for mapping complex traits.

genomics↗

bioRxiv2021

Genomic variations and epigenomic landscape of the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel

The teleost medaka (Oryzias latipes) is a well-established vertebrate model system, with a long history of genetic research, and multiple high-quality reference genomes available for several inbred strains (HdrR, HNI and HSOK). Medaka has a high tolerance to inbreeding from the wild, thus allowing one to establish inbred lines from wild founder individuals. We have exploited this feature to create an inbred panel resource: the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel. This panel of 80 near-isogenic inbred lines contains a large amount of genetic variation inherited from the original wild population. We used Oxford Nanopore Technologies (ONT) long read data to further investigate the genomic and epigenomic landscapes of a subset of the MIKK panel. Nanopore sequencing allowed us to identify a much greater variety of high-quality structural variants compared with Illumina sequencing. We also present results and methods using a pan-genome graph representation of 12 individual medaka lines from the MIKK panel. This graph-based reference MIKK panel genome revealed novel differences between the MIKK panel lines compared to standard linear reference genomes. We found additional MIKK panel-specific genomic content that would be missing from linear reference alignment approaches. We were also able to identify and quantify the presence of repeat elements in each of the lines. Finally, we investigated line-specific CpG methylation and performed differential DNA methylation analysis across the 12 lines. We thus present a detailed analysis of the MIKK panel genomes using long and short read sequence technologies, creating a MIKK panel specific pan genome reference dataset allowing for the investigation of novel variation types that would be elusive using standard approaches.

genomics↗