URee Chon

All Publications

• Inverse expression of Ten3 and Lphn2 across the developing mouse brain suggests a global strategy for circuit assembly. Current biology : CB Chon, U., Pederick, D. T., Song, J. H., Zhang, Y., Rana, I., Luo, L. 2026

  Abstract

  Precise wiring of neural circuits requires molecular strategies that ensure accurate target selection across diverse brain regions. Here, we identify inverse expression between a ligand-receptor pair, teneurin-3 (Ten3) and latrophilin-2 (Lphn2), across the developing mouse brain. Ten3 and Lphn2 exhibit inverse expression gradients along a retinotopic axis orthogonal to the ephrinA and EphA gradients, along the tonotopic axis across multiple brainstem auditory nuclei, and along the dorsomedial-ventrolateral axis in striatum and pallidum. Their inverse expression also creates discrete domains of cerebellar Purkinje cells (PCs) and cerebellar nuclei (CN). Using conditional-tag mice, we show that inverse Ten3 and Lphn2 expression patterns predict connectivity, following a "Ten3→Ten3, Lphn2→Lphn2" rule in all above circuits, and that Lphn2 is required in executing this rule in PCs→CN projection. Our findings suggest a global strategy of coordinating gene expression of key wiring molecules with circuit connectivity across the developing brain.

  View details for DOI 10.1016/j.cub.2026.04.037

  View details for PubMedID 42105756

• Aging drives cerebrovascular network remodeling and functional changes in the mouse brain. Nature communications Bennett, H. C., Zhang, Q., Wu, Y. T., Manjila, S. B., Chon, U., Shin, D., Vanselow, D. J., Pi, H. J., Drew, P. J., Kim, Y. 2024; 15 (1): 6398

  Abstract

  Aging is frequently associated with compromised cerebrovasculature and pericytes. However, we do not know how normal aging differentially impacts vascular structure and function in different brain areas. Here we utilize mesoscale microscopy methods and in vivo imaging to determine detailed changes in aged murine cerebrovascular networks. Whole-brain vascular tracing shows an overall ~10% decrease in vascular length and branching density with ~7% increase in vascular radii in aged brains. Light sheet imaging with 3D immunolabeling reveals increased arteriole tortuosity of aged brains. Notably, vasculature and pericyte densities show selective and significant reductions in the deep cortical layers, hippocampal network, and basal forebrain areas. We find increased blood extravasation, implying compromised blood-brain barrier function in aged brains. Moreover, in vivo imaging in awake mice demonstrates reduced baseline and on-demand blood oxygenation despite relatively intact neurovascular coupling. Collectively, we uncover regional vulnerabilities of cerebrovascular network and physiological changes that can mediate cognitive decline in normal aging.

  View details for DOI 10.1038/s41467-024-50559-8

  View details for PubMedID 39080289

  View details for PubMedCentralID PMC11289283

• In situ cell-type-specific cell-surface proteomic profiling in mice. Neuron Shuster, S. A., Li, J., Chon, U., Sinantha-Hu, M. C., Luginbuhl, D. J., Udeshi, N. D., Carey, D. K., Takeo, Y. H., Xie, Q., Xu, C., Mani, D. R., Han, S., Ting, A. Y., Carr, S. A., Luo, L. 2022

  Abstract

  Cell-surface proteins (CSPs) mediate intercellular communication throughout the lives of multicellular organisms. However, there are no generalizable methods for quantitative CSP profiling in specific cell types in vertebrate tissues. Here, we present in situ cell-surface proteome extraction by extracellular labeling (iPEEL), a proximity labeling method in mice that enables spatiotemporally precise labeling of cell-surface proteomes in a cell-type-specific environment in native tissues for discovery proteomics. Applying iPEEL to developing and mature cerebellar Purkinje cells revealed differential enrichment in CSPs with post-translational protein processing and synaptic functions in the developing and mature cell-surface proteomes, respectively. A proteome-instructed in vivo loss-of-function screen identified a critical, multifaceted role for Armh4 in Purkinje cell dendrite morphogenesis. Armh4 overexpression also disrupts dendrite morphogenesis; this effect requires its conserved cytoplasmic domain and is augmented by disrupting its endocytosis. Our results highlight the utility of CSP profiling in native mammalian tissues for identifying regulators of cell-surface signaling.

  View details for DOI 10.1016/j.neuron.2022.09.025

  View details for PubMedID 36220098

• In Situ Cell-Surface Proteomics: Method Development and Applications in Neurobiology Li, J., Han, S., Xie, Q., Shuster, S. A., Li, H., Udeshi, N. D., Svinkina, T., Carey, D. K., Mani, D. R., Xu, C., Guajardo, R., Chon, U., Luginbuhl, D. J., McLaughlin, C. N., Takeo, Y. H., Li, T., Orlin, D., Hu, M. C., Kohani, S., Wu, B., Xie, A., Kaewsapsak, P., Murthy, S. E., Quake, S. R., Carr, S. A., Ting, A. Y., Luo, L. ELSEVIER. 2022: S71

  View details for DOI 10.1016/j.mcpro.2022.100382

  View details for Web of Science ID 000898188800091

• Quantitative relationship between cerebrovascular network and neuronal cell types in mice CELL REPORTS Wu, Y., Bennett, H. C., Chon, U., Vanselow, D. J., Zhang, Q., Munoz-Castarieda, R., Cheng, K. C., Osten, P., Drew, P. J., Kim, Y. 2022; 39 (12): 110978

  Abstract

  The cerebrovasculature and its mural cells must meet brain regional energy demands, but how their spatial relationship with different neuronal cell types varies across the brain remains largely unknown. Here we apply brain-wide mapping methods to comprehensively define the quantitative relationships between the cerebrovasculature, capillary pericytes, and glutamatergic and GABAergic neurons, including neuronal nitric oxide synthase-positive (nNOS+) neurons and their subtypes in adult mice. Our results show high densities of vasculature with high fluid conductance and capillary pericytes in primary motor sensory cortices compared with association cortices that show significant positive and negative correlations with energy-demanding parvalbumin+ and vasomotor nNOS+ neurons, respectively. Thalamo-striatal areas that are connected to primary motor sensory cortices also show high densities of vasculature and pericytes, suggesting dense energy support for motor sensory processing areas. Our cellular-resolution resource offers opportunities to examine spatial relationships between the cerebrovascular network and neuronal cell composition in largely understudied subcortical areas.

  View details for DOI 10.1016/j.celrep.2022.110978

  View details for Web of Science ID 000820772300002

  View details for PubMedID 35732133

  View details for PubMedCentralID PMC9271215

• Quantitative relationship between the cerebrovascular network and neuronal cell types in mice Wu, Y., Bennett, H., Chon, U. R., Vanselow, D., Zhang, Q., Munoz-Castaneda, R., Cheng, K., Osten, P., Drew, P., Kim, Y. SAGE PUBLICATIONS INC. 2022: 316-317

  View details for Web of Science ID 000802263300536

• Cellular anatomy of the mouse primary motor cortex NATURE Munoz-Castaneda, R., Zingg, B., Matho, K. S., Chen, X., Wang, Q., Foster, N. N., Li, A., Narasimhan, A., Hirokawa, K. E., Huo, B., Bannerjee, S., Korobkova, L., Park, C., Park, Y., Bienkowski, M. S., Chon, U., Wheeler, D. W., Li, X., Wang, Y., Naeemi, M., Xie, P., Liu, L., Kelly, K., An, X., Attili, S. M., Bowman, I., Bludova, A., Cetin, A., Ding, L., Drewes, R., D'Orazi, F., Elowsky, C., Fischer, S., Galbavy, W., Gao, L., Gillis, J., Groblewski, P. A., Gou, L., Hahn, J. D., Hatfield, J. T., Hintiryan, H., Huang, J., Kondo, H., Kuang, X., Lesnar, P., Li, X., Li, Y., Lin, M., Lo, D., Mizrachi, J., Mok, S., Nicovich, P. R., Palaniswamy, R., Palmer, J., Qi, X., Shen, E., Sun, Y., Tao, H. W., Wakemen, W., Wang, Y., Yao, S., Yuan, J., Zhan, H., Zhu, M., Ng, L., Zhang, L., Lim, B., Hawrylycz, M., Gong, H., Gee, J. C., Kim, Y., Chung, K., Yang, X., Peng, H., Luo, Q., Mitra, P. P., Zador, A. M., Zeng, H., Ascoli, G. A., Huang, Z., Osten, P., Harris, J. A., Dong, H. 2021; 598 (7879): 159-+

  Abstract

  An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted1. Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization. We defined around two dozen projection neuron types in the MOp-ul and derived an input-output wiring diagram, which will facilitate future analyses of motor control circuitry across molecular, cellular and system levels. This work provides a roadmap towards a comprehensive cellular-resolution description of mammalian brain architecture.

  View details for DOI 10.1038/s41586-021-03970-w

  View details for Web of Science ID 000733963000017

  View details for PubMedID 34616071

  View details for PubMedCentralID PMC8494646

• Striatal Direct Pathway Targets Npas1<SUP>+</SUP> Pallidal Neurons JOURNAL OF NEUROSCIENCE Cui, Q., Du, X., Chang, I. Y. M., Pamukcu, A., Lilascharoen, V., Berceau, B. L., Garcia, D., Hong, D., Chon, U., Narayanan, A., Kim, Y., Lim, B., Chan, C. 2021; 41 (18): 3966-3987

  View details for DOI 10.1523/JNEUROSCI.2306-20.2021

  View details for Web of Science ID 000647691100004

• Mycobacterial HelD is a nucleic acids-clearing factor for RNA polymerase NATURE COMMUNICATIONS Kouba, T., Koval, T., Sudzinova, P., Pospisil, J., Brezovska, B., Hnilicova, J., Sanderova, H., Janouskova, M., Sikova, M., Halada, P., Sykora, M., Barvik, I., Novacek, J., Trundova, M., Duskova, J., Skalova, T., Chon, U. R., Murakami, K. S., Dohnalek, J., Krasny, L. 2020; 11 (1): 6419

  Abstract

  RNA synthesis is central to life, and RNA polymerase (RNAP) depends on accessory factors for recovery from stalled states and adaptation to environmental changes. Here, we investigated the mechanism by which a helicase-like factor HelD recycles RNAP. We report a cryo-EM structure of a complex between the Mycobacterium smegmatis RNAP and HelD. The crescent-shaped HelD simultaneously penetrates deep into two RNAP channels that are responsible for nucleic acids binding and substrate delivery to the active site, thereby locking RNAP in an inactive state. We show that HelD prevents non-specific interactions between RNAP and DNA and dissociates stalled transcription elongation complexes. The liberated RNAP can either stay dormant, sequestered by HelD, or upon HelD release, restart transcription. Our results provide insights into the architecture and regulation of the highly medically-relevant mycobacterial transcription machinery and define HelD as a clearing factor that releases RNAP from nonfunctional complexes with nucleic acids.

  View details for DOI 10.1038/s41467-020-20158-4

  View details for Web of Science ID 000608512400003

  View details for PubMedID 33339823

  View details for PubMedCentralID PMC7749160

• Disinhibition of somatostatin interneurons confers resilience to stress in male but not female mice NEUROBIOLOGY OF STRESS Jefferson, S. J., Feng, M., Chon, U. R., Guo, Y., Kim, Y., Luscher, B. 2020; 13: 100238

  Abstract

  Chronic stress represents a vulnerability factor for anxiety and depressive disorders and has been widely used to model aspects of these disorders in rodents. Disinhibition of somatostatin (SST)-positive GABAergic interneurons in mice by deletion of γ2 GABAA receptors selectively from these cells (SSTCre:γ2f/f mice) has been shown to result in behavioral and biochemical changes that mimic the responses to antidepressant doses of ketamine. Here we explored the extent to which SSTCre:γ2f/f mice exhibit resilience to unpredictable chronic mild stress (UCMS). We found that male SSTCre:γ2f/f mice are resilient to UCMS-induced (i) reductions in weight gain, (ii) reductions in SST-immuno-positive cells in medial prefrontal cortex (mPFC), (iii) increases in phosphorylation of eukaryotic elongation factor 2 (eEF2) in mPFC, and (iv) increased anxiety in a novelty suppressed feeding test. Female SSTCre:γ2f/f mice were resilient to UCMS-induced reductions in SST-immuno-positive cells indistinguishably from males. However, in contrast to males, they showed no UCMS effects on weight gain independent of genotype. Moreover, in mPFC of female γ2f/f control mice, UCMS resulted in paradoxically reduced p-EF2 levels without stress effects in the SSTCre:γ2f/f mutants. Lastly, female SSTCre:γ2f/f mice showed increased rather than reduced UCMS induced anxiety compared to γ2f/f controls. Thus, disinhibition of SST interneurons results in behavioral resilience to UCMS selectively in male mice, along with cellular resilience of SST neurons to UCMS independent of sex. Thus, mechanisms underlying vulnerability and resilience to stress are sex specific and map to mPFC rather than hippocampus but appear unrelated to changes in expression of SST as a marker of corresponding interneurons.

  View details for DOI 10.1016/j.ynstr.2020.100238

  View details for Web of Science ID 000612170000009

  View details for PubMedID 33344694

  View details for PubMedCentralID PMC7739040

• Topographically Distinct Projection Patterns of Early-Generated and Late-Generated Projection Neurons in the Mouse Olfactory Bulb ENEURO Chon, U., LaFever, B. J., Nguyen, U., Kim, Y., Imamura, F. 2020; 7 (6)

  Abstract

  In the mouse brain, olfactory information is transmitted to the olfactory cortex via olfactory bulb (OB) projection neurons known as mitral and tufted cells. Although mitral and tufted cells share many cellular characteristics, these cell types are distinct in their somata location and in their axonal and dendritic projection patterns. Moreover, mitral cells consist of heterogeneous subpopulations. We have previously shown that mitral cells generated at different embryonic days differentially localize within the mitral cell layer (MCL) and extend their lateral dendrites to different sublayers of the external plexiform layer (EPL). Here, we examined the axonal projection patterns from the subpopulations of OB projection neurons that are determined by the timing of neurogenesis (neuronal birthdate) to understand the developmental origin of the diversity in olfactory pathways. We separately labeled early-generated and late-generated OB projection neurons using in utero electroporation performed at embryonic day (E)11 and E12, respectively, and quantitatively analyzed their axonal projection patterns in the whole mouse brain using high-resolution 3D imaging. In this study, we demonstrate that the axonal projection of late-generated OB projection neurons is restricted to the anterior portion of the olfactory cortex while those of the early-generated OB projection neurons innervate the entire olfactory cortex. Our results suggest that the late-generated mitral cells do not extend their axons to the posterior regions of the olfactory cortex. Therefore, the mitral cells having different birthdates differ, not only in cell body location and dendritic projections within the OB, but also in their axonal projection pattern to the olfactory cortex.

  View details for DOI 10.1523/ENEURO.0369-20.2020

  View details for Web of Science ID 000657320100008

  View details for PubMedID 33158934

  View details for PubMedCentralID PMC7716433

• Quantitative cellular-resolution map of the oxytocin receptor in postnatally developing mouse brains NATURE COMMUNICATIONS Newmaster, K. T., Nolan, Z. T., Chon, U., Vanselow, D. J., Weit, A. R., Tabbaa, M., Hidema, S., Nishimori, K., Hammock, E. A. D., Kim, Y. 2020; 11 (1): 1885

  Abstract

  The oxytocin receptor (OTR) plays critical roles in social behavior development. Despite its significance, brain-wide quantitative understanding of OTR expression remains limited in postnatally developing brains. Here, we develop postnatal 3D template brains to register whole brain images with cellular resolution to systematically quantify OTR cell densities. We utilize fluorescent reporter mice (Otrvenus/+) and find that cortical regions show temporally and spatially heterogeneous patterns with transient postnatal OTR expression without cell death. Cortical OTR cells are largely glutamatergic neurons with the exception of cells in layer 6b. Subcortical regions show similar temporal regulation except the hypothalamus and two hypothalamic nuclei display sexually dimorphic OTR expression. Lack of OTR expression correlates with reduced dendritic spine densities in selected cortical regions of developing brains. Lastly, we create a website to visualize our high-resolution imaging data. In summary, our research provides a comprehensive resource for postnatal OTR expression in the mouse brain.

  View details for DOI 10.1038/s41467-020-15659-1

  View details for Web of Science ID 000558827500020

  View details for PubMedID 32313029

  View details for PubMedCentralID PMC7171089

• Npas1<SUP>+</SUP>-Nkx2.1<SUP>+</SUP> Neurons Are an Integral Part of the Cortico-pallido-cortical Loop JOURNAL OF NEUROSCIENCE Abecassis, Z. A., Berceau, B. L., Win, P. H., Garcia, D., Xenias, H. S., Cui, Q., Pamukcu, A., Cherian, S., Hernandez, V. M., Chon, U., Lim, B., Kim, Y., Justice, N. J., Awatramani, R., Hooks, B. M., Gerfen, C. R., Boca, S. M., Chan, C. 2020; 40 (4): 743-768

  Abstract

  Within the basal ganglia circuit, the external globus pallidus (GPe) is critically involved in motor control. Aside from Foxp2+ neurons and ChAT+ neurons that have been established as unique neuron types, there is little consensus on the classification of GPe neurons. Properties of the remaining neuron types are poorly defined. In this study, we leverage new mouse lines, viral tools, and molecular markers to better define GPe neuron subtypes. We found that Sox6 represents a novel, defining marker for GPe neuron subtypes. Lhx6+ neurons that lack the expression of Sox6 were devoid of both parvalbumin and Npas1. This result confirms previous assertions of the existence of a unique Lhx6+ population. Neurons that arise from the Dbx1+ lineage were similarly abundant in the GPe and displayed a heterogeneous makeup. Importantly, tracing experiments revealed that Npas1+-Nkx2.1+ neurons represent the principal noncholinergic, cortically-projecting neurons. In other words, they form the pallido-cortical arm of the cortico-pallido-cortical loop. Our data further show that pyramidal-tract neurons in the cortex collateralized within the GPe, forming a closed-loop system between the two brain structures. Overall, our findings reconcile some of the discrepancies that arose from differences in techniques or the reliance on preexisting tools. Although spatial distribution and electrophysiological properties of GPe neurons reaffirm the diversification of GPe subtypes, statistical analyses strongly support the notion that these neuron subtypes can be categorized under the two principal neuron classes: PV+ neurons and Npas1+ neurons.SIGNIFICANCE STATEMENT The poor understanding of the neuronal composition in the external globus pallidus (GPe) undermines our ability to interrogate its precise behavioral and disease involvements. In this study, 12 different genetic crosses were used, hundreds of neurons were electrophysiologically characterized, and >100,000 neurons were histologically- and/or anatomically-profiled. Our current study further establishes the segregation of GPe neuron classes and illustrates the complexity of GPe neurons in adult mice. Our results support the idea that Npas1+-Nkx2.1+ neurons are a distinct GPe neuron subclass. By providing a detailed analysis of the organization of the cortico-pallidal-cortical projection, our findings establish the cellular and circuit substrates that can be important for motor function and dysfunction.

  View details for DOI 10.1523/JNEUROSCI.1199-19.2019

  View details for Web of Science ID 000508635400005

  View details for PubMedID 31811030

  View details for PubMedCentralID PMC6975296

• Enhanced and unified anatomical labeling for a common mouse brain atlas NATURE COMMUNICATIONS Chon, U., Vanselow, D. J., Cheng, K. C., Kim, Y. 2019; 10: 5067

  Abstract

  Anatomical atlases in standard coordinates are necessary for the interpretation and integration of research findings in a common spatial context. However, the two most-used mouse brain atlases, the Franklin-Paxinos (FP) and the common coordinate framework (CCF) from the Allen Institute for Brain Science, have accumulated inconsistencies in anatomical delineations and nomenclature, creating confusion among neuroscientists. To overcome these issues, we adopt here the FP labels into the CCF to merge the labels in the single atlas framework. We use cell type-specific transgenic mice and an MRI atlas to adjust and further segment our labels. Moreover, detailed segmentations are added to the dorsal striatum using cortico-striatal connectivity data. Lastly, we digitize our anatomical labels based on the Allen ontology, create a web-interface for visualization, and provide tools for comprehensive comparisons between the CCF and FP labels. Our open-source labels signify a key step towards a unified mouse brain atlas.

  View details for DOI 10.1038/s41467-019-13057-w

  View details for Web of Science ID 000494938600001

  View details for PubMedID 31699990

  View details for PubMedCentralID PMC6838086