Biology subjects

Asakura, Y.

Publications and source records attributed to Asakura, Y..

9 recordsLinked to original sources

bioRxiv2026

Ultra-Slow Rhythmic Movement in the Elongating Tail of Xenopus Tadpoles

Since Darwins time, ultra-slow oscillatory movements have been recognized as a characteristic feature of axis elongation in plant organs such as shoots and tendrils, yet have not been reported in elongating animal body axes. Here, using long-term imaging of multiple anesthetized Xenopus laevis embryos with a modified document scanner, we identify a previously unrecognized ultra-slow rhythmic movement in the developing tadpole tail. This movement emerged during tailbud development, persisted once established, and occurred at an ultra-low frequency of approximately 10-4 Hz, several orders of magnitude slower than known active animal tail movements. Temperature-dependent imaging showed that its period varied with developmental rate and converged after time rescaling based on tail elongation rate, indicating a close link to morphogenetic elongation rather than conventional locomotor behavior. The timescale and physical context of this movement resemble plant circumnutation, in which slow organ-scale movement arises during constrained elongation. These findings suggest that slow rhythmic motion may represent a morphogenetic mode of animal movement and may be a recurrent dynamic feature of constrained elongation in living structures.

developmental biology↗

bioRxiv2025

A thermodynamic chromatin polymer model characterizes the epigenetic conditions for Hox collinearity.

Hox genes consist of four clusters, A, B, C, and D, each containing up to 13 paralogous genes. They are linearly arrayed on cluster regions in the same order as their expression timings along the anterior-posterior (A-P) axis development. This correspondence is known as temporal collinearity, and when the expression order of Hox genes is disrupted, the A-P axis is not accurately established. Although essential molecules and genomic regulatory elements for Hox collinearity have been identified, it remains unclear whether they act on individual genes or instead coordinate the cluster-wide sequential activation along the genomic order. To address this question, we developed a theoretical framework based on the statistical thermodynamics of chromatin modeled as a polymer, interpreting collinearity as a sequential opening of nucleosomes along the gene cluster. The model incorporates interactions between nucleosomes and DNA-binding factors, including transcription factors, represented by energy terms for binding and chromatin bridging. This formulation links the thermodynamic stability of chromatin states with the sequential opening process along the Hox clusters. Our model characterized key quantities that determine the order of chromatin opening and revealed intrinsic constraints that limit sequential opening of chromatin, underlying Hox collinearity. Significance statementHox collinearity, a remarkable correspondence between the genomic order and expression timing of Hox genes, provides cells with positional information on the anterior-posterior axis during development. Although essential molecules and genomic regulatory elements have been identified, the mechanism of sequential activation along the genomic order remains elusive. To address this question, we theoretically investigated the epigenetic states of chromatin using a chromatin polymer model in statistical thermodynamics. Our model provides a possible explanation for the sequential activation of the chromatin underlying Hox collinearity. This work bridges developmental genetics and statistical thermodynamics, offering a quantitative framework for understanding gene activation order along the genome.

biophysics↗

bioRxiv2025

Inverse modeling unveils governing law of mechano-chemical dynamics of epithelial migration

Collective cell migration is fundamental to tissue homeostasis and underlies biological processes such as wound healing and cancer invasion. Previous work has proposed governing equations to describe how chemical and mechanical inputs regulate these movements, but the quantitative validity of such models remains to be thoroughly assessed. Here, we developed a machine-learning framework that infers the governing equation from live-cell imaging data. Applied to epithelial sheet migration driven by MAPK/ERK, our approach quantitatively predicted single-cell movement from local chemical and mechanical cues. Examination of the learned equations further indicated that cells process environmental signals by computing their spatiotemporal derivatives. Moreover, when applied to individual cells, our framework revealed cell-cell heterogeneity in the underlying migratory rules. Our framework offers a powerful tool for predictive modeling of multicellular dynamics in both physiological and pathological settings.

systems biology↗

bioRxiv2025

JAG2-related muscular dystrophy and Notch signaling dysfunction in muscle stem cells

We previously identified a muscular dystrophy caused by biallelic variants in JAG2, whose protein product Jagged2 is a canonical Notch ligand. However, the disease mechanism remains unclear, particularly with respect to muscle stem cell (MuSC) function and muscle regeneration. We examined the consequences of JAG2 deficiency and modeled pathogenic JAG2 variants in vitro and in vivo, the latter in mouse and fly models and with particular attention to the MuSC-muscle endothelial cell (MuEC) niche. We found that both Jag2 deficiency and overexpression of pathogenic JAG2 variants impaired Notch signaling and myogenic self-renewal and differentiation. Hypomorphic Jag2 mutant (Jag2sm) mice display depleted MuSCs, corresponding with impaired muscle regeneration in those mice. Co-culture experiments and the examination of cell-type-specific Jag2 conditional knockout mice demonstrated that MuEC-specific Jag2 knockout resulted in reduced MuSC self-renewal, while MuSC-specific Jag2 knockout resulted in reduced myogenic differentiation. Human reference JAG2, but not human pathogenic variants of JAG2, rescued the deficiency of Serrate (Ser), the Drosophila ortholog of JAG2. Therefore, pathogenic variants in JAG2 impair muscle development and regeneration through disrupted cell-autonomous cis- inhibition and non-autonomous trans-activation involving Notch signaling dysfunction. Our findings indicate that optimizing JAG2-mediated Notch signaling is a potential therapeutic approach for JAG2-related muscular dystrophy.

developmental biology↗

bioRxiv2021

Endothelial cell signature in muscle stem cells showed by VEGFA-FLT1-AKT1 axis for muscle stem cell survival

Endothelial and skeletal muscle lineages arise from common embryonic progenitors. Despite their shared developmental origin, adult endothelial cells (ECs) and muscle stem cells (MuSCs) (satellite cells) have been thought to possess distinct gene signatures and signaling pathways. Here we shift this paradigm by uncovering how adult MuSC behavior is affected by the expression of a subset of EC transcripts. We used several computational analyses including single-cell RNAseq to show that MuSCs express low levels of canonical EC markers. We demonstrate that MuSC survival is regulated by one such prototypic endothelial signaling pathway (VEGFA-FLT1). Using pharmacological and genetic gain- and loss-of-function studies, we identify the FLT1-AKT1 axis as the key effector underlying VEGFA-mediated regulation of MuSC survival. All together, our data support that the VEGFA-FLT1-AKT1 pathway promotes MuSC survival during muscle regeneration, and highlights how the minor expression of select transcripts is sufficient for affecting cell behavior.

developmental biology↗

bioRxiv2020

Circadian timing-dependent myoblast differentiation and muscle regeneration

Circadian rhythms regulate cell proliferation and differentiation but circadian control of tissue regeneration remains elusive at the molecular level. Here, we show that proper myoblast differentiation and muscle regeneration are regulated by the circadian master regulators Per1 and Per2. Depletion of Per1 or Per2 suppressed myoblast differentiation in vitro and muscle regeneration in vivo, demonstrating their non-redundant functions. Both Per1 and Per2 were required for the activation of Igf2, an autocrine promoter of myoblast differentiation, accompanied by Per-dependent recruitment of RNA polymerase II, dynamic histone modifications at the Igf2 promoter and enhancer, and the promoter-enhancer interaction. This circadian epigenetic priming created a preferred time window for initiating myoblast differentiation. Consistently, muscle regeneration was faster if initiated at night when Per1, Per2, and Igf2 were highly expressed compared with morning. This study reveals the circadian timing as a significant factor for effective muscle cell differentiation and regeneration. eTOC SummaryKatoku-Kikyo et al. show that the circadian master regulators Per1 and Per2 control the efficiency of myoblast differentiation via Igf2 activation. This pathway creates a preferred circadian time window for myoblast differentiation in vitro and muscle regeneration in vivo.

developmental biology↗

bioRxiv2020

Co-expressed subunits of dual genetic origin define a conserved supercomplex mediating essential protein import into chloroplasts

In photosynthetic eukaryotes, thousands of proteins are translated in the cytosol and imported into the chloroplast through the concerted action of two translocons — termed TOC and TIC — located in the outer and inner membranes of the chloroplast envelope, respectively. The degree to which the molecular composition of the TOC and TIC complexes is conserved over phylogenetic distances has remained controversial. Here, we combine transcriptomic, biochemical, and genetic tools in the green alga Chlamydomonas (Chlamydomonas reinhardtii) to demonstrate that, despite a lack of evident sequence conservation for some of its components, the algal TIC complex mirrors the molecular composition of a TIC complex from Arabidopsis thaliana. The Chlamydomonas TIC complex contains three nuclear-encoded subunits, Tic20, Tic56 and Tic100, and one chloroplast-encoded subunit, Tic214, and interacts with the TOC complex, as well as with several uncharacterized proteins to form a stable supercomplex (TicToc), indicating that protein import across both envelope membranes is mechanistically coupled. Expression of the nuclear and chloroplast genes encoding both known and the here newly identified TicToc components is highly coordinated, suggesting that a mechanism for regulating its biogenesis across compartmental boundaries must exist. Conditional repression of Tic214, the only chloroplast-encoded subunit in the TicToc complex, impairs the import of chloroplast proteins with essential roles in chloroplast ribosome biogenesis and protein folding and induces a pleiotropic stress response, including several proteins involved in the chloroplast unfolded protein response. These findings underscore the functional importance of the TicToc supercomplex in maintaining chloroplast proteostasis.Competing Interest StatementThe authors have declared no competing interest.View Full Text

plant biology↗

bioRxiv2019

Hierarchical modeling of mechano-chemical dynamics of epithelial sheets across cells and tissue

Collective cell migration is a macroscopic population-level phenomenon that has emerged across hierarchy from mi-croscopic interactions between cells; however, the underlying mechanism remains unclear. Here, we targeted epithe-lial collective cell migration, driven by the mechanical force regulated by chemical signals of traveling ERK activation waves, observed in wound healing. We propose a hierarchical mathematical framework for understanding how cells are orchestrated through mechanochemical cell-cell interaction. We mathematically transformed a particle-based model at the cellular level into a continuum model at the tissue level. The continuum model described relationships between cell migration and mechanochemical variables, namely, ERK activity gradients, cell density, and velocity field, which could be compared with live-cell imaging data. The continuum model recapitulated the ERK wave-induced collective cell migration in wound healing. We also numerically confirmed a consistency between the two models. This framework allows us to connect hierarchical causality from the single-cell level to the tissue level.

biophysics↗

bioRxiv2019

Amelioration of muscular dystrophy phenotype in mdx mice by inhibition of Flt1

Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disease in which the dystrophin coding for a membrane stabilizing protein is mutated. Recently, the vasculature has also shown to be perturbed in DMD and DMD model mdx mice. Data-mining DMD transcriptomics revealed the defects were correlated to a vascular endothelial growth factor (VEGF) signaling pathway. To reveal the relationship between DMD and VEGF signaling, mdx mice were crossed with constitutive (CAG/CreERTM:Flt1LoxP/LoxP) and endothelial cell-specific conditional gene knockout mice (Cdh5CreERT2:Flt1LoxP/LoxP) for Flt1 which is a decoy receptor for VEGF. Previous work demonstrated that heterozygous global Flt1 knockout mice increased vascular density and improved DMD phenotypes when crossed with DMD model mdx and mdx:utrn-/- mice. Here, we showed that while constitutive deletion of Flt1 is detrimental to the skeletal muscle function, endothelial cell-specific Flt1 deletion resulted in increased vascular density and improvement in the DMD-associated phenotype in the mdx mice. These decreases in pathology, including improved muscle histology and function, were recapitulated in mdx mice given anti-FLT1 peptides or monoclonal antibodies, which blocked VEGF-FLT1 binding. The histological and functional improvement of dystrophic muscle by FLT1 blockade provides a novel pharmacological strategy for the potential treatment of DMD.

developmental biology↗