Biology subjects

Okano, H. J.

Publications and source records attributed to Okano, H. J..

3 recordsLinked to original sources

bioRxiv2026

MECP2-mutant marmosets exhibit primate-specific phenotypes of Rett syndrome

We used genome editing to generate MECP2-knockout marmosets and establish a new primate model for Rett syndrome (RTT), a neurodevelopmental disorder. MRI analysis of this marmoset model revealed diminished cortico-cortical connections, particularly those originating in the prefrontal cortex. Detailed histological analysis revealed reduced dendritic arborization and synaptic density, particularly in the upper layers of the cerebral cortex. Cortical layer II/III excitatory neurons appeared to be immature based on single-nucleus RNA sequencing and spatial transcriptomics, while PVALB-positive interneurons exhibited upregulation of neuronal maturation-related transcripts. Moreover, the neurodevelopmental disease gene GABAB receptor 2 (GABBR2) emerged as a conserved downstream target of MECP2, illuminating a cellular cascade that could be targeted in preclinical and therapeutic drug development. Many of the gene expression changes observed in the marmoset model are common in RTT patients, thereby highlighting molecular links from cell type-specific phenotypes in the marmoset model to the RTT clinical presentation.

neuroscience↗

bioRxiv2023

Activity-regulated micro-exon splicing programs underlie late-onset plasticity at the axon initial segment

The axon initial segment (AIS) is a specialized neuronal compartment located at the proximal end of axons and initiates action potentials. AIS undergoes plastic changes with aging, disease, and activity levels; however, the molecular mechanisms underlying their plasticity remain unclear. We discovered that depolarization induces diffuse elongation of the AIS in cerebellar granule cells over the span of days via the Ca2+-dependent ERK/MAP kinase pathway. These structural changes were accompanied by a decrease in voltage-gated Na+ channel density, resulting in a homeostatic attenuation in neuronal excitability. Notably, we found that the late-onset AIS plasticity is associated with depolarization-induced alternative splicing of smaller exons (<100 nt) of transcripts encoding AIS-enriched proteins. In addition, depolarization-induced the skipping of the 53-nt exon19 from the transcript of the splicing protein Rbfox1. CRISPR-mediated removal of exon 19 from Rbfox1 promoted its nuclear localization and sequentially induced a series of downstream micro-exon splicing changes in several AIS proteins, recapitulating cerebellar AIS plasticity. In a Rbfox1-independent mechanism, depolarization-induced insertion of the developmentally regulated micro-exon 34 into the key AIS scaffolding protein Ankyrin G (AnkG). The constitutive insertion of exon 34 into AnkG disrupted its interaction with the AIS cytoskeletal protein {beta}IV spectrin and induced plastic changes in the AIS. Our findings provide fundamental mechanistic insights into the activity-mediated late-onset plasticity of AIS, highlighting the power of micro-scale splicing events in the homeostatic regulation of axonal remodeling.

neuroscience↗

bioRxiv2020

The Japan Monkey Centre Primates Brain Imaging Repository of high-resolution postmortem magnetic resonance imaging: the second phase of the archive of digital records

A comparison of neuroanatomical features of the brain between humans and our evolutionary relatives, nonhuman primates, is key to understanding the human brain system and the neural basis of mental and neurological disorders. Although most comparative MRI studies of human and nonhuman primate brains have been based on brains of primates that had been used as subjects in experiments, it is essential to investigate various species of nonhuman primates in order to elucidate and interpret the diversity of neuroanatomy features among humans and nonhuman primates. To develop a research platform for this purpose, it is necessary to harmonize the scientific contributions of studies with the standards of animal ethics, animal welfare, and the conservation of brain information for long-term continuation of the field. In previous research, we first developed an open-resource repository of anatomical images obtained using 9.4-T ex vivo MRI of postmortem brain samples from 12 nonhuman primate species, and which are stored at the Japan Monkey Centre. In the present study, as a second phase, we released a collection of T2-weighted images and diffusion tensor images obtained in nine species: white-throated capuchin, Bolivian squirrel monkey, stump-tailed macaque, Tibet monkey, Sykes monkey, Assamese macaque, pig-tailed macaque, crested macaque, and chimpanzee. Our image repository should facilitate scientific discoveries in the field of comparative neuroscience. This repository can also promote animal ethics and animal welfare in experiments with nonhuman primate models by optimizing methods for in vivo and ex vivo MRI scanning of brains and supporting veterinary neuroradiological education. In addition, the repository is expected to contribute to conservation, preserving information about the brains of various primates, including endangered species, in a permanent digital form.

neuroscience↗