Biology subjects

Omura, M.

Publications and source records attributed to Omura, M..

5 recordsLinked to original sources

bioRxiv2026

Functional Profiling of a Human Odorant Receptor Using Olfactory Cilia Links its Activation to Odor Quality

The mechanism governing singular odorant receptor (OR) gene choice restricts each olfactory sensory neuron (OSN) to expressing a single OR allele from a repertoire of more than 1,100 receptor genes. Consequently, only a small fraction of OSNs express any given OR, limiting studies of OR function, axonal wiring, and odor coding. Here, we show that multimerizing a 21-bp homeodomain enhancer dramatically increases the probability of receptor choice. We engineered a single-copy Olfr151 minigene carrying a 9x21 enhancer and the human odorant receptor OR10G4, integrated at a genomic site distant from all endogenous OR clusters. This transgene drives singular OR10G4 expression in approximately 75% of OSNs and is accompanied by widespread reductions in endogenous Class I, Class II, and TAAR receptor transcripts and proteins, indicating that cis-regulatory elements govern the probability of OR selection. The abundance of OR10G4-expressing cilia enabled highly sensitive ligand screening using CELIA (Cilia-based Evaluation of Ligands and receptor InterActions). Profiling guaiacol derivatives revealed a strong correspondence among receptor activation, cAMP production, and published human psychophysical responses. Although OR10G4 responds to guaiacol-related odorants, multiple canonical vanilla odorants failed to activate the receptor, arguing against a primary role in vanilla perception. Instead, the lowest EC50 ligands were enriched for compounds human subjects described as smoky. Together, these findings link activation of a single human odorant receptor to a defined perceptual odor-quality dimension and establish a general strategy for decoding the molecular basis of human odor perception.

neuroscience↗

bioRxiv2026

The mitochondrial genome of the hammerhead flatworm Bipalium nobile and its phylogenetic implications

We sequenced the nearly complete mitochondrial genome of the hammerhead flatworm Bipalium nobile Kawakatsu and Makino, 1982 using short-read sequencing technology, yielding a 16,018 bp genome comprising 12 protein-coding genes, 22 tRNA genes, and 2 rRNA genes. The composition and order of genes were consistent with those observed in the closely related species Bipalium kewense and Diversibipalium multilineatum, except for the position of tRNA-Glu. Phylogenetic analysis based on all mitochondrial proteins from species within the family Geoplanidae supports the monophyly of a clade comprising B. nobile, B. kewense, and D. multilineatum. The mitochondrial genome sequence obtained in this study provides a valuable resource for investigating the genetic diversity and population structure of B. nobile, a soil-dwelling predator with the potential for global spread as an invasive organism.

zoology↗

bioRxiv2022

Commonality of Odorant Receptor Choice Mechanism Revealed by Analysis of a Highly Represented Odorant Receptor Transgene

In the mouse, more than 1,100 odorant receptors (ORs) are expressed in a monogenic and monoallelic fashion, referred to as singular gene expression. Using a 21bp singular-choice enhancer (x21), we radically increase representation of olfactory sensory neurons (OSNs) choosing a 5x21 enhanced OR transgene, but not overexpression of its mRNA on a per cell basis. RNA-sequencing and differential expression analysis identified 425 differentially expressed genes (DEGs). ORs make up 86% of all DEGs, of which 325 have decreased representation and 40 have increased representation. Underrepresented ORs include Class I, Class II and TAAR genes and within each of their respective olfactory bulb domains: DI, DII, and DIII (TAAR) we committedly observe multiple homogeneous glomeruli with an OR1A1-identity. The underrepresentation of endogenous, class-specific ORs across evolutionarily distinct cell types in favor of the expression of the 5x21-OR1A1 transgene argues that a common mechanism of singular gene choice is present for all OR-expressing OSNs.

neuroscience↗

bioRxiv2021

A Genetic Platform for Functionally Profiling Odorant Receptors Ex Vivo Using Olfactory Cilia.

The molecular basis for odor perception in humans remains an enigma as odorant receptors (ORs) are notoriously difficult to study outside of their native environment. Efforts toward OR expression and functional profiling have been met with limited success due to poor efficiency of in vitro cell surface expression. Olfactory cilia are known to contain all components of the olfactory signal transduction machinery and can be placed into an ex vivo well-plate assay to rapidly measure robust, reproducible odor-specific responses. We now describe the isolation of cilia from mouse nose bioreactors for two human ORs, OR1A1 and OR5AN1, and reveal 10-100 fold more sensitivity compared to previously reported assays. A single animal can produce up to 4,000 384-well assay wells, and isolated olfactory cilia can be stored frozen and thus preserved. This pipeline offers a sensitive, highly scalable ex vivo odor screening platform that opens the door for decoding human olfaction. One Sentence Summaryolfactory-cilia based odor screening platform.

neuroscience↗

bioRxiv2018

Brain folding is initiated by mechanical constraints without a cellular pre-pattern

During human brain development the cerebellum and cerebral cortex fold into robust patterns that increase and compartmentalize neural circuits. Although differential expansion of elastic materials has been proposed to explain brain folding, the cellular and physical processes responsible at the time of folding have not been defined. Here we used the murine cerebellum, with 8-10 folds, as a tractable model to study brain folding. At folding initiation we considered the cerebellum as a bilayer system with a fluidlike outer layer of proliferating precursors and an incompressible core. We discovered that there is no obvious cellular pre-pattern for folding, since when folding initiates, the precursors within the outer layer have uniform sizes, shapes and proliferation, as well as a distribution of glial fibers. Furthermore, although differential expansion is created by the outer layer expanding faster than the core at folding initiation, thickness variations arise in the outer layer that are inconsistent with elastic material models. A multiphase model was applied that includes radial and circumferential tension and mechanical constraints derived from in vivo measurements. Our results demonstrate that cerebellar folding emerges from mechanical forces generated by uniform cell behaviors. We discuss how our findings apply to human cerebral cortex folding.

developmental biology↗