Biology subjects

Imoto, D.

Publications and source records attributed to Imoto, D..

5 recordsLinked to original sources

bioRxiv2026

Adhesion-mediated transition to a mesenchymal-like, fan-shaped migration mode in Dictyostelium discoideum

Cells migrate with varying degrees of polarization and directional persistence as exemplified by epithelial, mesenchymal and amoeboid cell types. Depending on the physiological and developmental context, these states are often interchangeable, reflecting the plastic and adaptive nature of the cytoskeleton. However, general principles governing such motility-mode transitions remain poorly established, and it is unclear whether they apply to non-metazoan cells. Here, we report previously overlooked features of the amoebozoan Dictyostelium discoideum, demonstrating that it undergoes pronounced adhesion-dependent changes in both motility and morphology. Unlike the well-known pseudopodia-rich forms observed on weakly adhesive surfaces, cells on highly adhesive substrates adopt fan-shaped morphologies reminiscent of cultured mesenchymal cells. These cells are characterized by lamellipodia-like protrusions enriched in the SCAR/WAVE complex, large focal adhesion-like plaques, F-actin-independent front-rear gradients of Ras/Rap activity. Furthermore, they exhibit a marked increase in cortical stiffness dependent on F-actin, talins, and the RhoA homolog RacE. Their high directional persistence depends on the persistent localization of the SCAR/WAVE complex, talin-mediated substrate anchoring, and RacE-dependent stabilization of the cell rear. We propose that adhesion-engaged remodeling of cell polarity and cortical mechanics is an evolutionarily ancient feature that predates the specialization of adhesion receptors.

cell biology↗

bioRxiv2023

Random walk and cell morphology dynamics in Naegleria gruberi

Amoeboid cell movement and migration are wide-spread across various cell types and species. Microscopy-based analysis of the model systems Dictyostelium and neutrophils over the years have uncovered generality in their overall cell movement pattern. Under no directional cues, the centroid movement can be quantitatively characterized by their persistence to move in a straight line and the frequency of re-orientation. Mathematically, the cells essentially behave as a persistent random walker with memory of two characteristic time-scale. Such quantitative characterization is important from a cellular-level ethology point of view as it has direct connotation to their exploratory and foraging strategies. Interestingly, outside the amoebozoa and metazoa, there are largely uncharacterized species in the excavate taxon Heterolobosea including amoeboflagellate Naegleria. While classical works have shown that these cells indeed show typical amoeboid locomotion on an attached surface, their quantitative features are so far unexplored. Here, we analyzed the cell movement of Naegleria gruberi by employing long-time phase contrast imaging to automatically track individual cells. We show that the cells move as a persistent random walker with two time-scales that are close to those known in Dictyostelium and neutrophils. Similarities were also found in the shape dynamics which is characterized by the appearance, splitting and annihilation of the curvature waves along the cell edge. Our analysis based on the Fourier descriptor and a neural network classifier point to importance of morphology features unique to Naegleria including complex protrusions and the transient bipolar dumbbell morphologies.

cell biology↗

bioRxiv2020

Comparative mapping of crawling-cell morphodynamics in deep learning-based feature space

Navigation of fast migrating cells such as amoeba Dictyostelium and immune cells are tightly associated with their morphologies that range from steady polarized forms that support high directionality to those more complex and variable when making frequent turns. Model simulations are essential for quantitative understanding of these features and their origins, however systematic comparisons with real data are underdeveloped. Here, by employing deep-learning-based feature extraction combined with phase-field modeling framework, we show that a low dimensional feature space for 2D migrating cell morphologies obtained from the shape stereotype of keratocytes, Dictyostelium and neutrophils can be fully mapped by interlinked signaling network of cell-polarization and protrusion dynamics. Our analysis links the data-driven shape analysis to the underlying causalities by identifying key parameters critical for migratory morphologies both normal and aberrant under genetic and pharmacological perturbations. The results underscore the importance of deciphering self-organizing states and their interplay when characterizing morphological phenotypes.

cell biology↗

bioRxiv2020

Activation of prodynorphin neurons in the dorsomedial hypothalamus inhibits food intake and promotes positive valence

The regulation of food intake is one of the major research areas in the study of metabolic syndromes such as obesity. Gene targeting studies have clarified the roles of hypothalamic neurons in feeding behaviour. However, our understanding of neural function under physiological conditions is still limited. Immediate early genes, such as activity-regulated cytoskeleton-associated protein (Arc/Arg3.1), are useful markers of neuronal activity. Here, we investigated the role of Arc/Arg3.1 gene-expressing neurons in the hypothalamus after refeeding using the targeted recombination in active populations method. We identified refeeding-responsive prodynorphin/cholecystokinin neurons in the dorsomedial hypothalamus that project to the paraventricular hypothalamic nucleus. Chemogenetic activation of these neurons decreased food intake and promoted positive valence. Our findings provide insight into the role of newly identified hedonic neurons in the process of feeding-induced satiety.

physiology↗

bioRxiv2020

Prostaglandin in the ventromedial hypothalamus regulates peripheral glucose metabolism

The hypothalamus plays a central role in monitoring and regulating systemic glucose metabolism. The brain is enriched with phospholipids containing poly-unsaturated fatty acids, which are biologically active in physiological regulation. Here, we show that intraperitoneal glucose injection induced changes in hypothalamic distribution and amount of phospholipids, especially arachidonic-acid-containing phospholipids, that were then metabolized to produce prostaglandins. Knockdown of cytosolic phospholipase A2 (cPLA2), a key enzyme for generating arachidonic acid from phospholipids, in the hypothalamic ventromedial nucleus (VMH), lowered insulin sensitivity in muscles during regular chow diet (RCD) feeding. Conversely, the down-regulation of glucose metabolism by high fat diet (HFD) feeding was improved by knockdown of cPLA2 in the VMH through changing hepatic insulin sensitivity and hypothalamic inflammation. Our data suggest that cPLA2-mediated hypothalamic phospholipid metabolism is critical for controlling systemic glucose metabolism during RCD, while continuous activation of the same pathway to produce prostaglandins during HFD deteriorates glucose metabolism.

physiology↗