Biology subjects

Yim, H.

Publications and source records attributed to Yim, H..

8 recordsLinked to original sources

bioRxiv2026

Terminal selector and subtype selector function across 200 million years of nematode evolution

The evolution of brains is subject to investigation in many different animal groups, each offering unique advantages to advance our understanding of the cellular, molecular and regulatory substrates of evolutionary change. Here, we use two nematode species, C. elegans and P. pacificus, separated by more than 200 million years of evolution to explore how neuronal cell types and the regulatory programs instructing the identity of these cell types have evolved over time. Using gene expression pattern analysis, we compare the differentiation programs of over half of all nematode neuron classes. To explore how the gene regulatory architecture of neuronal differentiation programs evolves, we apply our deep understanding of neuronal differentiation programs, controlled by terminal selectors and subtype selectors in C. elegans. Through mutant analysis of orthologous P. pacificus regulatory factors, we elucidate patterns of conservation and novelties over such substantial evolutionary distance. We discovered striking similarities in terminal selector expression and activities throughout the nervous system but also observed that terminal selectors can acquire novel sites of expression and distinct regulatory capabilities, manifested by changes in effector gene expression and, hence, neuronal phenotypes. Our mutant analysis argues for a buffering of terminal selector function and for an evolutionary lability of differences in closely related neuronal subtypes. Taken together, our analysis reveals molecular substrates of evolutionary change in nervous systems.

neuroscience↗

bioRxiv2026

Coexistence of phasmid sensory neurons and caudal glands offers a new perspective on cell type evolution in nematodes

The highly conserved body plan of nematodes makes members of this phylum excellent models to study cell type evolution. Early branching nematode lineages, mostly occupying aquatic habitats, usually contain caudal glands deployed for underwater attachment to a substrate, but have been thought to lack phasmid sensory organs, resulting in their historical classification as "Aphasmidia". With the transition to a terrestrial environment, nematodes lost caudal glands and gained phasmid sensory neurons. The supposed mutually exclusive existence of caudal glands and phasmids has led to the suggestion that phasmid neurons may have evolved from caudal glands. Here, we rule out this possibility through light and electron microscopical analysis of Mononchus aquaticus, a member of the early branching Dorylaimia lineage, showing that phasmid sensory neurons and caudal glands do coexist. This observation not only argues against a proposed cell type evolution scenario accompanying aquatic-to-terrestrial transitions but also indicates that the presence of phasmid sensory organs may have been an ancestral trait of the nematode phylum.

evolutionary biology↗

bioRxiv2025

Identity and functions of monoaminergic neurons in the predatory nematode Pristionchus pacificus reveal nervous system conservation and divergence

Changes in neurotransmitter usage in homologous neurons may drive evolutionary adaptations in neural circuits across animal phylogeny. The predatory nematode Pristionchus pacificus can be used as a model system to examine nervous system evolution by comparing neurotransmitter expression with that of C. elegans and other nematodes. Here we characterize P. pacificus neurotransmitter expression and function in specific neurons, focusing on its complete set of monoaminergic neurons. We discover patterns of conservation as well as novelties. We examine the roles of monoamines in specific behaviors using neurotransmitter synthesis and vesicular transporter mutants, finding possible differences in the control of host-finding and dispersal behavior.

neuroscience↗

bioRxiv2024

Structural diversity of mitochondria in the neuromuscular system across development

As an animal matures, its neural circuit undergoes alterations, yet the developmental changes in intracellular organelles to facilitate these changes is less understood. Using 3D electron microscopy and deep learning, we developed semi-automated methods for reconstructing mitochondria in C. elegans and collected mitochondria reconstructions from normal reproductive stages and dauer, enabling comparative study on mitochondria structure within the neuromuscular system. We found that various mitochondria structural properties in neurons correlate with synaptic connections and these properties are preserved across development in different neural circuits. To test the necessity of these universal mitochondria properties, we examined the behavior in drp-1 mutants with impaired mitochondria fission and discovered that it caused behavioral deficits. Moreover, we observed that dauer neurons display distinctive mitochondrial features, and mitochondria in dauer muscles exhibit unique reticulum-like structure. We propose that this specialized mitochondria structure may serve as an adaptive mechanism to support stage-specific behavioral and physiological needs.

neuroscience↗

bioRxiv2024

Discovery of the First-in-class G9a/GLP PROTAC Degrader

Aberrantly expressed lysine methyltransferases G9a and GLP, which catalyze mono- and di-methylation of histone H3 lysine 9 (H3K9), have been implicated in numerous cancers. Recent studies have uncovered both catalytic and non-catalytic oncogenic functions of G9a/GLP. As such, G9a/GLP catalytic inhibitors have displayed limited anticancer activity. Here, we report the discovery of the first-in-class G9a/GLP proteolysis targeting chimera (PROTAC) degrader, 10 (MS8709), as a potential anticancer therapeutic. 10 induces G9a/GLP degradation in a concentration-, time, and ubiquitin-proteasome system (UPS)-dependent manner, does not alter the mRNA expression of G9a/GLP and is selective for G9a/GLP over other methyltransferases. Moreover, 10 displays superior cell growth inhibition to the parent G9a/GLP inhibitor UNC0642 in prostate, leukemia, and lung cancer cells and has suitable mouse pharmacokinetic properties for in vivo efficacy studies. Overall, 10 is a valuable chemical biology tool to further investigate the functions of G9a/GLP and a potential therapeutic for treating G9a/GLP-dependent cancers. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=127 SRC="FIGDIR/small/582210v1_ufig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@1b3c923org.highwire.dtl.DTLVardef@5a22f0org.highwire.dtl.DTLVardef@1abbabeorg.highwire.dtl.DTLVardef@1711f29_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2023

Mind of a dauer: Comparative connectomics reveals developmental plasticity

A fundamental question in neurodevelopmental biology is how flexibly the nervous system changes during development. To address this, we reconstructed the complete connectome of dauer, an alternative developmental stage of nematodes with distinct behavioral characteristics, by volumetric reconstruction and automated synapse detection using deep learning. With the basic architecture of the nervous system preserved, structural changes in neurons, large or small, were closely associated with connectivity changes, which in turn evoked dauer-specific behaviors such as nictation. Graph theoretical analyses revealed significant dauer-specific rewiring of sensory neuron connectivity and increased clustering within motor neurons in the dauer connectome. We suggest that the nervous system in the nematode, probably animals in general, has evolved to respond to harsh environments by reversibly developing a quantitatively and qualitatively differentiated connectome.

neuroscience↗

bioRxiv2022

Negative Impact of Daily Screen Use on Inhibitory Control Network in Preadolescence: A Two Year Follow-Up Study

The COVID-19 pandemic has made an unprecedented shift in childrens daily lives. Children are increasingly spending time with screens to learn and connect with others. As the online environment rapidly substitutes in-person experience, understanding childrens neuropsychological trajectories associated with screen experiences is important. Previous findings suggest that excessive screen use can lead children to prefer more immediate rewards over delayed outcomes. We hypothesized that increased screen time delays a childs development of inhibitory control. By analyzing neuropsychological data from 8,324 children (9-11ys) from the ABCD Study, we found that children who had more screen time showed a higher reward orientation and a weaker inhibitory control system (i.e., fronto-striatal circuitry) in the brain. Importantly, we found that the interaction between screen exposure and reward sensitivity negatively influenced the development of the inhibitory control system in the brain over a two year period. These results indicate possible negative long-term impacts of increased daily screen time on childrens neuropsychological development. The results further demonstrated that screen time influences dorsal striatum connectivity, which suggests that the effect of daily screen use is a habitual seeking behavior. The study provides neural and behavioral evidence on the negative impact of daily screen use on developing children.

neuroscience↗

bioRxiv2021

The C. elegans DAF-19M module: a shift from general ciliogenesis to ciliary and behavioral specialization

In animals, cilia are important for the interaction with environments and the proper function of tissues and organs. Understanding the distinctive identities of each type of ciliated cell is essential for therapeutic solutions for ciliopathies, complex disorders with impairments of various organs caused by defective cilia development and function. Here, we report a regulatory module consisting of a cascade of transcription factors and their target genes that confer the cell type-specific ciliary identities on the IL2 ciliated neurons in C. elegans. We found that DAF-19M, isoform of the sole C. elegans RFX transcription factor DAF-19, through X-box promoter motif variants, heads a regulatory module in IL2 neurons, comprising the core target genes klp-6 (kinesin), osm-9 (TRP channel), and cwp-4 (novel); under the overall control of terminal selector proteins UNC-86 and CFI-1. Considering the conservation of this DAF-19M module in IL2 neurons for nictation, a dauer larva-specific behavior, and in male-specific neurons for mating behavior, we propose the existence of an evolutionarily adaptable, hard-wired genetic module for distinct behaviors that share the feature "recognizing the environment."

molecular biology↗