Biology subjects

Shiraki, T.

Publications and source records attributed to Shiraki, T..

6 recordsLinked to original sources

bioRxiv2026

Basal ganglia output guides decision-making by state destabilization

To execute learned behavior, the nervous system can undergo an activity-state transition between the current and the learned activity states. Here, using adult zebrafish, we show that their basal ganglia output induces such state transitions for goal-directed behavior. After learning the Go/No-go task in virtual reality, the striatal indirect pathway responds to negative values of a conditioned cue and the absence of sensory feedback by different neuronal populations. The pallidal output pathway integrates these negative value signals and then broadcasts the integrated signal to the Dc area in the pallium (fish cortex). Optogenetics and mathematical modeling suggested that this pallidal output activity uniformly destabilizes ongoing Dc activity states, thereby facilitating behavioral state transitions toward the behavioral state with the minimum pallidal output activity. This mechanism explains how pallidal output activity guides goal-directed behavior beyond potential barriers between activity states underlying different behavioral states.

neuroscience↗

bioRxiv2026

RNA polymerase loss by nuclear rupture drives LMNA cardiomyopathy

Localized rupture of the nuclear envelope has recently been reported in various pathologies, including cancer 1,2, neurodegenerative disease 3-5, myocardial infarction 6, as well as dilated cardiomyopathy caused by Lamin A/C gene mutations (LMNA-DCM) 7. Whether and how nuclear rupture contributes to disease remains unknown. Here, we report that nuclear rupture causes global transcriptional deficiency in a mouse model of LMNA-DCM. We observed that ruptured nuclei lost RNA polymerase II, leading to downregulation of numerous genes essential for cardiomyocyte structure and function. We identified endogenous resealing of nuclear rupture as a cardioprotective mechanism in LMNA-DCM mouse hearts. Resealing involved the ESCRT-III membrane remodeling complex recruited to nuclear rupture sites. Resealed nuclei restored transcription while inhibiting ESCRT-III activity accelerated cardiomyopathy. However, resealed nuclei were short-lived: they re-ruptured at twice the rate of resealing. A kinetic model predicted progressive accumulation of ruptured nuclei despite ongoing resealing. Consistently, a human LMNA-DCM heart contained numerous ruptured nuclei at disease presentation. These findings linked nuclear rupture to organ deterioration through global transcriptional deficiency and suggested rupture resealing as a critical modifier of nuclear rupture-associated conditions.

molecular biology↗

bioRxiv2025

Molecular and functional dissection using CaMPARI-seq reveals the neuronal organization for dissociating optic flow-dependent behaviors

Optic flow processing is critical for the visual control of body and eye movements in many animals. Rotational and translational binocular optic flow patterns need to be clearly distinguished to induce different behavior outputs. However, the specific neuron types and their connectivity involved in this computation remain unclear. Here, we developed a method to link the functional labeling using a photoconvertible calcium indicator called CaMPARI2 and single-cell RNA-sequencing (CaMPARI-seq) to investigate the transcriptional profile of the pretectum, a center for processing optic flow in larval zebrafish. Using this technique, we identified a pretectal cluster expressing tcf7l2, which can be further classified into molecularly distinct subclusters. In vivo calcium imaging and cell ablation revealed that nkx1.2lb-positive pretectal neurons are commissural inhibitory neurons required for the optomotor response but not for the optokinetic response. Our genetic and functional dissection using CaMPARI-seq uncovered the neuronal organization essential for dissociating different optic flow-dependent behaviors.

neuroscience↗

bioRxiv2025

Th9-endothelial cell crosstalk promotes inflammatory atherosclerotic cardiovascular disease

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death, and understanding its pathogenic drivers is critical for effective prevention and treatment. Inflammation has a critical role in ASCVD, and patients with inflammatory diseases are at increased risk. However, the key inflammatory mediator promoting ASCVD are incompletely understood, a major barrier when targeting inflammation to prevent ASCVD. Here, we found that interleukin-9 (IL-9) producing T helper cells (Th9) were significantly associated with ASCVD in patients with the autoimmune disease psoriasis. Th9 cells were poised to migrate to coronary vessels and were identified in atherosclerotic plaque. In vivo, murine inflammatory atherogenesis was prevented by IL-9 blockade and by IL-9 receptor (IL-9R) deletion in endothelial cells. In human arterial endothelial cells, IL-9R/STAT3 signaling promoted endothelial dysfunction, angiogenesis, and release of leukocyte chemoattractants. These findings suggest that in autoimmune diseases like psoriasis, Th9/IL-9 promote atherosclerosis by directly targeting endothelial cells, and that IL-9R/STAT3 signaling could be a promising therapeutic target for ASCVD. eTOC SummaryBaral et. al. investigate individuals who are at high risk for atherosclerosis due to underlying inflammatory disease and use mouse models of cardiovascular disease to uncover a role for interleukin-9-producing T helper 9 cells in the pathogenesis of inflammatory atherosclerosis.

immunology↗

bioRxiv2023

Transgenic tools targeting striatal and pallidal subpopulations revealed evolutionary conservation and specialization of the cortico-basal ganglia circuit in zebrafish

The cortico-basal ganglia circuit mediates decision-making. Here, we generated transgenic tools for adult zebrafish targeting specific subpopulations of the components of this circuit and utilized them to identify evolutionary homologs of the mammalian direct- and indirect-pathway striatal neurons which respectively project to the homologs of the internal and external segment of the globus pallidus (dEN and Vl) as in mammals. Unlike in mammals, the Vl mainly projected to the dEN directly, not by way of the subthalamic nucleus. Further single-cell RNA sequencing analysis revealed two pallidal output pathways: a major shortcut pathway directly connecting the dEN with the pallium and the evolutionarily conserved closed loop by way of the thalamus. Our resources and circuit map provide the common basis for the functional study of the basal ganglia in a small and optically tractable zebrafish brain for the comprehensive mechanistic understanding of the cortico-basal ganglia circuit.

neuroscience↗

bioRxiv2021

Foxq2 determines blue cone identity in zebrafish

Most vertebrate lineages retain a tetrachromatic visual system, which is supported by a functional combination of spectrally distinct multiple cone photoreceptors, UV, blue, green, and red cones. The blue cone identity is ensured by selective expression of blue (sws2) opsin, and the mechanism is poorly understood because SWS2 gene has been lost in mammalian species such as mouse, whose visual system has been extensively studied. Here we pursued loss-of-function studies on transcription factors expressed predominantly in zebrafish cone photoreceptors and identified Foxq2 as a core factor driving sws2 gene expression. foxq2 is expressed only in the blue cone, and loss of foxq2 selectively abolishes sws2 expression. Comparative genomic analysis revealed that a wide range of vertebrate species retain both FOXQ2 and SWS2 genes. We propose that FOXQ2-dependent SWS2 expression is a prevalent regulatory mechanism that was acquired at the early stage of vertebrate evolution

neuroscience↗