Biology subjects

Toida, K.

Publications and source records attributed to Toida, K..

3 recordsLinked to original sources

bioRxiv2026

The Nkx2.3-Nr5a1 gene cascade plays a crucial role in spleen-specific vascular architecture and marginal zone formation

NR5A1 is a nuclear receptor and master regulator of steroidogenic tissue development and steroid hormone biosynthesis in the adrenal glands and gonads. Although NR5A1 is expressed in splenic vascular endothelial cells, its function in the adult spleen remains unclear. Using single-cell transcriptomics in mice, we show that NR5A1-positive endothelial cells are heterogeneous and exhibit distinct phenotypes according to their localization in the splenic sinus or marginal sinus. To assess NR5A1 function, we generated a spleen-specific Nr5a1 enhancer deletion model. Enhancer loss resulted in reduced spleen size and ablation of the marginal zone and marginal sinus. In addition, 21-hydroxylase activity in splenic sinusoidal endothelial cells was reduced, particularly in females, leading to decreased levels of adrenocortical steroids in the spleen. Enhancer deletion also induced ectopic lymphatic-like and high endothelial venule-like vasculature similar to those observed in Nkx2.3-deficient mice. Consistently, mutation of the NKX2.3-binding motif within the enhancer abolished NR5A1 expression. Together, these findings identify an Nkx2.3[->]Nr5a1 regulatory axis essential for spleen-specific endothelial cell differentiation and splenic architecture required for blood filtration and marginal zone formation.

developmental biology↗

bioRxiv2022

The dgc2 gene encoding di-guanylate cyclase suppresses both motility and biofilm formation in the filamentous cyanobacterium Leptolyngbya boryana.

Colony pattern formations of bacteria with motility manifest complicated morphological self-organization phenomena. Leptolyngbya boryana is the filamentous cyanobacterial species, which has been used as a genetic model organism for studying metabolism including photosynthesis and nitrogen-fixation. Although a widely used type strain (wild type) of this species has not been reported to show any motile activity, we isolated a spontaneous mutant strain which shows active motility (gliding activity) to give rise to complicated colony patters, including comet-like wandering clusters and disk-like rotating vortices on solid media. Whole-genome resequencing identified multiple mutations on the genome in the mutant strain. We confirmed that inactivation of a candidate gene, dgc2 (LBDG_02920), in the wild type background was sufficient to give rise to motility and the morphological colony patterns. This gene encodes a protein, containing the GGDEF motif, which is conserved at the catalytic domain of diguanylate cyclase (DGC). Although DGC has been reported to be involved in biofilm formation, the mutant strain lacking dgc2 significantly facilitated biofilm formation, suggesting a role of DGC for suppressing both gliding motility and biofilm formation. Thus, L. boryana provides an excellent genetic model to study dynamic colony pattern formation, and novel insight on a role of c-di-GMP for biofilm formation. ImportanceSelf-propelled bacteria often show complicated collective behaviors, such as the formation of dense moving clusters, which is exemplified by wandering comet-like and rotating disk-like colonies, while molecular details of forming such structures remain limited. We found that a strain deficient in the diguanylate cyclase gene dgc2 in the filamentous cyanobacterium L. boryana induces motility, complex and dynamic colony pattern formation including the comet-like and disk-like clusters. While c-di-GMP has been reported to activate biofilm formation in some bacterial species, disruption of the dgc2 gene unexpectedly enhanced it, providing a novel role for c-di-GMP regulatory system in both colony pattern formation and biofilm formation.

microbiology↗

bioRxiv2020

Maturation of complex synaptic connections of layer 5 cortical axons in the posterior thalamic nucleus requires SNAP25

Synapses are able to form in the absence of neuronal activity, but how is their subsequent maturation affected in the absence of regulated vesicular release? We explored this question using 3D electron microscopy and immuno electron microscopy analyses in the large, complex synapses formed between cortical sensory efferent axons and dendrites in the posterior thalamic nucleus. Using a Snap25 conditional knockout we found that during the first two postnatal weeks the axonal boutons emerge and increase in the size similar to the control animals. However, by P18, when an adult-like architecture should normally be established, axons were significantly smaller with 3D reconstructions showing that each Snap25-cko bouton only forms a single synapse with the connecting dendritic shaft. No excrescences from the dendrites were formed, and none of the normally large glomerular axon endings were seen. These results show that activity mediated through regulated vesicular release from the presynaptic terminal is not necessary for the formation of synapses, but it is required for the maturation of the specialised synaptic structures between layer 5 corticothalamic projections in Po.

neuroscience↗