Biology subjects

Yoshizaki, K.

Publications and source records attributed to Yoshizaki, K..

5 recordsLinked to original sources

bioRxiv2026

Left-right asymmetry of the microminipig brain.

Left-right asymmetry of the brain is well recognized in various animals including C. elegans, drosophila and zebrafish. In primates, most of the brain studies describe side of the brain. However, in spite of huge amounts of accumulating rodent studies on neuroscience, most of rodent studies do not distinguish the brain side. The pig brain is considered to occupy an intermediate position between primates and rodents in terms of structural complexity and brain function. Moreover, the numbers of studies using genetic manipulation of pigs are drastically increasing. So, we investigated microminipig (MMP) brain mesoscopic anatomy focusing on left-right differences of its morphology. Here, we show the anterior cingulate cortex, perirhinal cortex, and cerebellum of male and female MMPs, are structurally asymmetrical. The cerebellar vermis, paravermis is tilted from the midline and the consequently the cerebellar cortex exhibits asymmetrical morphology. The anterior cingulate gurus exhibited protrusion and invagination toward the midline on the right and left side, respectively. The left perirhinal lobe exhibited distinct patterns of cortical gyration between left and right side. These data demonstrate that MMPs are one of the suitable model animals for investigating cerebral and cerebellar asymmetry.

neuroscience↗

bioRxiv2025

Impaired store-operated Ca2+ entry in mouse epidermis leads to reduced epidermal barrier function via Klk activation.

Store-operated Ca2+ entry (SOCE) is a mechanism by which STIM1/2 detect calcium depletion in the endoplasmic reticulum (ER) and activate ORAI1/TRPC channels on the cell membrane to induce calcium influx into the cytoplasm. This study aimed to investigate SOCEs role in the skin epidermis in vivo, using female mice with epithelial tissue-specific Stim1 and Stim2 knockout (Stim1/2 cKO) and control mice (Stim1/2fl/fl). Keratinocytes from Stim1/2 cKO mice exhibited reduced Stim1 and Stim2 gene expression levels and impaired SOCE function compared with the controls. Histological analysis revealed hyperkeratosis in the Stim1/2 cKO tissues; however, no significant changes were observed in the proliferation or migration of keratinocytes or wound healing of the back skin. RNA-seq analysis indicated altered keratinization and cell-to-cell adhesion in the Stim1/2 cKO mice. Additionally, transepidermal water loss (TEWL) was increased significantly, and a biotinylated reagent diffused from the subcutaneous area into the granular layer, signifying compromised barrier function in the Stim1/2 cKO mice. The Stim1/2 cKO mice exhibited alterations in desmoglein 1 (Dsg1) and elevated levels of Kallikrein-related peptidase (Klk) 6 and Klk7, leading to increased trypsin- and chymotrypsin-like serine protease activities, respectively. These results suggest that SOCE dysfunction leads to hyperkeratosis and impaired epidermal barrier function via Klk activation without affecting skin cell proliferation in vivo. These novel findings improve understanding of the molecular mechanisms underlying calcium signaling in the epidermis barrier and suggest potential avenues for investigating related skin pathologies linked to calcium homeostasis, such as Hailey-Hailey disease (HHD) and Darier disease (DD).

cell biology↗

bioRxiv2022

Mediator 1 ablation induces enamel-to-hair lineage conversion through enhancer dynamics

Postnatal cell fate has been postulated to be primarily determined by the local tissue microenvironment. Here, we found that Mediator 1 (Med1) dependent epigenetic mechanisms dictate tissue-specific lineage commitment and progression of dental epithelia. Deletion of Med1, a key component of the Mediator complex linking enhancer activities to gene transcription, provokes a tissue extrinsic lineage shift, causing hair generation in the dental environment. Med1 deficiency gives rise to unusual hair growth via primitive cellular aggregates on incisors. Mechanistically, we found that Med1 establishes super-enhancers that control enamel lineage transcription factors in dental stem cells and their progenies. However, Med1 deficiency reshapes the enhancer landscapes and causes a switch from the dental epithelial transcriptional program towards hair and epidermis on incisors in vivo, and in dental epithelial stem cells in vitro. Med1 loss also provokes an increase in the number and size of enhancers. Interestingly, control dental epithelia already exhibit enhancers for hair and epidermal key transcription factors; these expand in size and transform into active super-enhancers upon Med1 loss suggesting that these epigenetic mechanisms cause the transcriptomic and phenotypic shift towards epidermal and hair lineages. Thus, we propose a role for Med1 in safeguarding lineage specific enhancers, highlight the central role of enhancer accessibility and usage in lineage reprogramming and provide new insights into ectodermal regeneration.

developmental biology↗

bioRxiv2019

Paternal aging affects the developmental patterns of ultrasonic vocalization induced by maternal separation in neonatal mice individually

Infant crying is an innate communicative behavior that is frequently impaired in certain neurodevelopmental disorders (NDDs). Since advanced paternal age is a reported risk factor for NDDs in offspring, we evaluated the impact of a fathers age on early vocal development in C57BL/6J mice. We recorded and applied a unique combination of computational analyses to ultrasonic vocalizations (USVs) emitted by mouse pups sired by young and aged fathers. Our data showed that advanced paternal age reduced the number and duration of USVs, and altered the syllable composition in pups. Moreover, pups born to young fathers showed convergent vocal characteristics with a rich repertoire during postnatal development, while those born to aged fathers exhibited more divergent vocal patterns with limited repertoire. Principal component analysis in conjunction with clustering analysis demonstrated that pups from aged fathers deviated from typical trajectories of vocal development, which were considered as atypical individuals. Thus, our study indicates that advanced paternal age has a significant effect on offsprings early vocal development. It is suggested that the trajectories of vocal development could be a useful marker of the NDD-like phenotype associated with the advanced paternal age. In addition, our comprehensive computational analysis described here is an effective approach to characterize the altered individual diversity relevant to neurodevelopmental disorders. One Sentence SummaryAdvanced paternal age affects vocal development in early postnatal mice, with more pups showing atypical developmental trajectories.

neuroscience↗

bioRxiv2019

Paternal age affects offspring's behavior possibly via an epigenetic mechanism recruiting a transcriptional repressor REST

Advanced paternal age has deleterious effects on mental health of next generation. Using a mouse model, we have confirmed that offspring derived from aged fathers showed impairments in behavior and abnormalities in the brain structure and activity. Comprehensive target DNA methylome analyses revealed in aged sperm more hypo-methylated genomic regions, in which REST/NRSF binding motif was enriched. Gene set enrichment analyses also identified enrichment of "REST/NRSF target genes", in addition to "Late-fetal genes" and autism spectrum disorder-related "SFARI genes", in up-regulated genes of developing brains from aged father. Indeed, gene sets near hypo-methylated genomic regions with REST/NRSF binding motif were also enriched in up-regulated genes of developing brains. Taken altogether, DNA hypo-methylation due to paternal aging in sperm will induce leaky expression of REST/NRSF target genes in the developing brain, thereby causing neuronal abnormalities and subsequent behavioral alteration in offspring.

neuroscience↗