Biology subjects

Ishimaru, Y.

Publications and source records attributed to Ishimaru, Y..

6 recordsLinked to original sources

bioRxiv2026

Early origin of sugar sensing in jawed vertebrates

Sweet taste guides animals to consume carbohydrate-rich foods, and many different vertebrate groups, from fish to mammals, rely on sugar-rich fruits or nectar produced by flowering plants (angiosperms). Although the genes encoding T1R2-T1R3, the receptor pair that mammals use to sense sugars, exist in the genomes of many vertebrates, their functions are unclear--and whether sugar sensing arose once early in vertebrate evolution or independently in different lineages after angiosperms evolved is currently unknown. Here, we combined ancestral reconstruction and receptor functional profiling to examine the evolutionary history of T1R taste receptors--including recently-described non-canonical receptors--across all major vertebrate clades. Our results pinpoint the origin of sugar sensing to before the emergence of angiosperms and uncover a myriad of alternative T1R-based sugar-sensing mechanisms, suggesting multiple independent T1R trajectories and revealing uncharted sensory diversity across vertebrates.

evolutionary biology↗

bioRxiv2026

Neural correlates of licking behavior modulated by target position in the striatal matrix compartment

The striatum is a major cortical input site of the basal ganglia and plays a critical role in the control of orofacial movements such as licking. However, how striatal activity relates to the spatial features of licking behavior remains unclear. In this study, we examined whether neural activity in the striatal matrix and striosomal compartments is associated with the spatial position of a licking target during an operant task. Head-fixed mice performed a licking task in which the target positions were varied across three spatial dimensions. Using fiber photometry in Calb1-IRES-Cre and Pdyn-IRES-Cre mice, we recorded calcium signals from matrix and striosomal neurons. Associations between neural activity, target position, and behavioral variables were quantified using linear mixed-effects modeling with cross-validation. Matrix activity prior to licking onset was primarily associated with the dorsal-ventral target position and reaction time. During licking, matrix activity was modulated by anterior-posterior and medial-lateral positions, independent of reaction time and lick count. In contrast, striosomal activity during licking was predominantly associated with the dorsal-ventral position. These findings demonstrate that neural matrix activity is systematically associated with spatial features of licking behavior, with distinct contributions before and during movement. Our results suggest that striatal matrix circuits provide task-relevant spatial signals for the control of orofacial actions. Significant StatementWe show that neural activity in the striatal matrix is associated with the three-dimensional position of a licking target during an operant task. Activity prior to licking onset reflects dorsal-ventral position, whereas activity during licking is modulated by the anterior-posterior and medial-lateral positions. These findings indicate that matrix activity represents spatial aspects of licking behavior, supporting a role for the striatum in integrating motor execution with task-specific spatial information and pointing to the matrix compartment as a substrate for transforming spatial coordinates into action-specific motor commands.

neuroscience↗

bioRxiv2025

Structural basis of stereochemical promiscuity by an umami taste receptor ortholog, Tas1r1/Tas1r3 from pufferfish

Taste receptor type 1 (TAS1R), which consists of sweet and umami receptors in humans, senses nutrients (such as sugars and amino acids) with substrate specificity that is often broad and varies among animals and subtypes. However, the structural basis for achieving diverse specificities remains largely elusive. Here, we present the crystal structure of the ligand-binding domain (LBD) of Tas1r1/Tas1r3 heterodimer from pufferfish, an ortholog of the human umami taste receptor. The overall structure of Tas1r1/Tas1r3LBD resembles previously reported TAS1R structures, indicating a conserved core architecture within the family. Nevertheless, pufferfish Tas1r1/Tas1r3 was found to bind and respond to both L- and D-amino acids, even though TAS1Rs are considered to respond to either enantiomer. Structural and mutational analyses revealed that this non-rigorous stereochemical recognition is attributed to inter- subdomain interactions that latch the cleft containing the amino acid-binding site. These interactions prevent the cleft from fully opening, thereby stabilizing the active conformation, even if the ligand shares a different chirality. These results suggest that different substrate specificities in TAS1Rs can be acquired not only by the gain or loss of direct interactions with the substrate but also by the gain of intramolecular interactions, which alter the conformational equilibrium of the receptor.

biochemistry↗

bioRxiv2025

Neural responses prior to licking onset in the striatal matrix compartment in mice

Licking is a continuous tongue thrust observed during drinking in rodents and humans and is often studied as an essential tongue movement for feeding and swallowing. The striatum, a component of the basal ganglia, plays a critical role in licking onset; however, it is unclear how the two compartments of the striatum--the matrix and striosomes--contribute to the control of licking onset. In this study, we used male and female transgenic mice that selectively expressed Cre recombinase in matrix or striosome neurons and subjected them to operant conditioning based on licking of a spout, during which neuronal activity in both compartments was measured using fiber photometry. Only matrix neurons showed responses prior to licking onset. In addition, the matrix neural response before licking onset was larger when mice licked a spout ipsilateral to the recording hemisphere of the brain than that observed when licking the contralateral spout. This response was observed similarly in mice conditioned to receive a reward regularly and those conditioned to receive a reward randomly, suggesting that the response was unrelated to whether the reward was predictable or unpredictable. Matrix neural activity was negatively correlated with the number of licks during the water intake behavior following the first lick. These findings suggest that matrix neurons are involved in the preparatory process for licking onset as well as in the regulation of licking frequency during water intake. Significant StatementThis study demonstrated that during the expression of operant conditioning behaviors based on licking, striatal matrix neurons showed responses prior to licking onset. Additionally, these responses were larger when the mouse licked the spout ipsilateral to the brain hemisphere undergoing recording than when a spout in the contralateral direction was licked. This result was also true for mice conditioned using either regular or random reward conditions. Additionally, the number of licks during water ingestion behavior following the initial lick was negatively correlated with matrix neuron activity. These changes in matrix neuron activity are suggested to be involved in the preparatory process for licking onset, independent of reward prediction, and in the regulation of licking frequency during drinking.

neuroscience↗

bioRxiv2023

Latent taste diversity revealed by a vertebrate-wide catalogue of T1R receptors

Taste is a vital chemical sense for feeding behavior. In mammals, the umami and sweet taste receptors are composed of three members of the taste receptor type 1 (T1R/TAS1R) family: T1R1, T1R2, and T1R3. Because their functional homologs exist in teleosts, only three TAS1R genes generated by gene duplication are believed to have been inherited from the common ancestor of bony vertebrates. Here, we report five previously uncharacterized TAS1R members in vertebrates, named TAS1R4, 5, 6, 7, and TAS1Rcf, through a genome-wide survey of diverse taxa. For TAS1R2 and TAS1R3, mammalian and teleost fish genes were found to be paralogous. Phylogenetic analysis suggests that the bony vertebrate ancestor had nine TAS1Rs due to multiple gene duplications, and some TAS1Rs were lost independently in each lineage; ultimately, mammals and teleosts have retained only three TAS1Rs, whereas other lineages have retained more TAS1Rs. Functional assays and expression analysis in non-teleost fishes suggest that the novel T1Rs form heterodimers in taste receptor cells and contribute to the recognition of a broad range of ligands such as essential amino acids, including branched-chain amino acids, which were not previously considered as T1R ligands. These results highlight an unexpected diversity of taste sensations in both modern and the ancestors of vertebrates. The complex evolution of the taste receptor family might have enabled vertebrates to adapt to diverse habitats on Earth.

evolutionary biology↗

bioRxiv2020

Cricket genomes: the genomes of future food

Most of our knowledge of insect genomes comes from Holometabolous species, which undergo the complete metamorphosis and have genomes under 2Gb with little signs of DNA methylation. In contrast, Hemiemetabolous insects undergo the ancestral incomplete metamorphosis and have larger genomes with high levels of DNA methylation. Hemimetabolous species from the Orthopteran order (grasshoppers and crickets) have some of the largest insect genomes. What drives the evolution of these unusual insect genome sizes, remains unknown. Here we report the sequencing, assembly and annotation of the 1.66-Gb genome of the Mediterranean field cricket Gryllus bimaculatus, and the annotation of the 1.60-Gb genome of the Hawaiian cricket Laupala kohalensis. We compare these two cricket genomes with those of 14 additional insects, and find evidence that hemimetabolous genomes expanded due to transposable element activity. Based on the ratio of observed to expected CpG sites, we find higher conservation and stronger purifying selection of methylated genes than non-methylated genes. Finally, our analysis suggests an expansion of the pickpocket class V gene family in crickets, which we speculate might play a role in the evolution of cricket courtship, including their characteristic chirping.

genomics↗