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
  • 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