Biology subjects

Mishina, T.

Publications and source records attributed to Mishina, T..

4 recordsLinked to original sources

bioRxiv2025

Century-old ethanol-preserved Vega Collection reveal the unexpected phylogeography of Slender bitterling Tanakia lanceolata in Japan

Recent genetic advancements offer new opportunities for studying natural history museum collections. The genetic analysis of century-old aquatic animal specimens, mostly preserved in ethanol, can provide valuable insights into the changes in genetic diversity caused by anthropogenic impacts. However, knowledge of the characteristics of degraded DNA from such specimens remains limited. In this study, we evaluated the DNA quality of bitterling fish, Tanakia lanceolata (Temminck and Schlegel), collected during the Vega Expedition in Japan in 1879 and preserved in ethanol. We then performed genomic analysis to test its hypothesized translocation-involved population history. The historical DNA was degraded, peaking around 50 bp, but a minor fraction exceeded 300 bp. Mitochondrial genetic analysis revealed high genetic similarity between the eastern and western sides of the Central Highland, typically impeding the dispersal of primary freshwater fish. These findings suggest an unexpected dispersal ability in T. lanceolata or undocumented translocations before the large-scale domestic translocations recorded since the 1910s. The customized workflow for historical ethanol-preserved specimens, based on historical DNA quality in this study, provides a foundation for studying historical archives.

evolutionary biology↗

bioRxiv2025

Kif11-haploinsufficient oocytes reveal spatially differential requirements for chromosome biorientation in the spindle

Bipolar spindle assembly and chromosome biorientation are prerequisites for chromosome segregation during cell division. The kinesin motor KIF11 drives spindle bipolarization by sliding antiparallel microtubules bidirectionally, elongating a spherical spindle into a bipolar-shaped structure in oocytes. This process stretches chromosomes, establishing chromosome biorientation at the spindle equator. The quantitative requirement for KIF11 in spindle bipolarization and chromosome biorientation remains unclear. Here, using a genetic strategy to modulate KIF11 expression levels, we show that Kif11 haploinsufficiency impairs spindle elongation, leading to the formation of a partially bipolarized spindle during meiosis I in mouse oocytes. While the partially bipolarized spindle allows chromosome stretching in the inner region of its equator, it fails to do so in the outer region. These findings demonstrate the necessity of biallelic functional Kif11 for bipolar spindle assembly in oocytes and reveal a spatially differential requirement for chromosome biorientation within the spindle.

cell biology↗

bioRxiv2024

Transcriptomic Signatures of WNT-Driven Pathways and Granulosa Cell-Oocyte Interactions during Primordial Follicle Activation

Primordial follicle activation (PFA) is a pivotal event in female reproductive biology, coordinating the transition from quiescent to growing follicles. This study employed comprehensive single-cell RNA sequencing to gain insights into the detailed regulatory mechanisms governing the synchronized dormancy and activation between granulosa cells (GCs) and oocytes with the progression of the PFA process. Wntless (Wls) conditional knockout (cKO) mice served as a unique model, suppressing the transition from pre-GCs to GCs, and disrupting somatic cell-derived WNT signaling in the ovary. Our data revealed immediate transcriptomic changes in GCs post-PFA in Wls cKO mice, leading to a divergent trajectory, while oocytes exhibited modest transcriptomic alterations. Subpopulation analysis identified the molecular pathways affected by WNT signaling on GC maturation, along with specific gene signatures linked to dormant and activated oocytes. Despite minimal evidence of continuous up-regulation of dormancy-related genes in oocytes, the loss of WNT signaling in (pre-)GCs impacted gene expression in oocytes even before PFA, subsequently influencing them globally. The infertility observed in Wls cKO mice was attributed to compromised GC-oocyte molecular crosstalk and the microenvironment for oocytes. Our study highlights the pivotal role of the WNT-signaling pathway and its molecular signature, emphasizing the importance of intercellular crosstalk between (pre-)GCs and oocytes in orchestrating folliculogenesis. Author summaryIn mammalian ovaries, primordial follicles protect dormant oocytes from wasteful consumption. We explored the complex molecular dynamics of the critical process of primordial follicle activation (PFA) that underlies female reproductive health, with a focus on the role of WNT signaling. By utilizing a unique mouse model with disrupted WNT signaling, our study reveals novel insights into the regulatory dynamics of granulosa cells (GCs) and oocytes during PFA. Single-cell transcriptome profiling uncovered distinct cell populations and highlighted the impact of WNT signaling on ovarian cell types. This study reveals distinct transcriptomic changes in GCs post-PFA, which affects their differentiation trajectories and highlights the critical role of WNT signaling in establishing GC function. We further examined the consequences of disrupted microenvironments on oocytes and GC-oocyte interactions, which elucidated altered oocyte subclusters and potential links to infertility. These findings provide a foundation for understanding the connections between WNT signaling and ovarian function. Our comprehensive analysis contributes valuable knowledge to reproductive biology, emphasizing the clinical relevance of WNT signaling in female fertility.

bioinformatics↗

bioRxiv2018

NRSF-mediated repression of neuronal genes in developing brain persists in the absence of NRSF-Sin3 interaction

Repression of target genes by the transcriptional repressor neuronal restrictive silencing factor (NRSF)/repressor element 1 silencing transcription factor (REST) contributes to enduring plasticity in the developing brain. However, the cofactor(s) interacting with NRSF to enable target gene repressor are not well understood, and may vary among neuronal populations and brain regions as well as with different contexts. Here we employed the novel designer drug mS-11 to block the interactions of the cofactor Sin3 with NRSF. We tested if NRSF-Sin3 interaction is required for repression of NRSF target genes in developing hypothalamus after activity-dependent modulation of NRSF function. In the hypothalamus in vitro, blocking glutamatergic neurotransmission robustly increased NRSF binding to the target gene Crh, resulting in its repression. Blocking the binding of NRSF to the chromatin with decoy NRSE-oligodeoxynucleotides abrogated this repression. In contrast, mS-11 at several concentrations did not impede Crh repression. NRSF-mediated repression may underlie disease processes such as the onset of epilepsy. Therefore, identifying small-molecule antagonists of NRSF is crucial for the development of disease-preventing or modifying interventions.

neuroscience↗