Brainwide Genetic Sparse Cell Labeling to Illuminate the Morphology of Neurons and Glia with Cre-Dependent MORF Mice.

Autor:	Veldman MB; Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, and Department of Psychiatry and Biobehavioral Sciences, Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA., Park CS; Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, and Department of Psychiatry and Biobehavioral Sciences, Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA., Eyermann CM; Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, and Department of Psychiatry and Biobehavioral Sciences, Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA., Zhang JY; Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, and Department of Psychiatry and Biobehavioral Sciences, Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA., Zuniga-Sanchez E; Department of Biological Chemistry, Howard Hughes Medical Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA., Hirano AA; Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Veterans Administration of Greater Los Angeles Health System, Los Angeles, CA 90073, USA., Daigle TL; Allen Institute for Brain Science, Seattle, WA 98109, USA., Foster NN; Center for Integrative Connectomics, University of Southern California Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, USC, Los Angeles, CA, 90033, USA., Zhu M; Center for Integrative Connectomics, University of Southern California Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, USC, Los Angeles, CA, 90033, USA., Langfelder P; Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, and Department of Psychiatry and Biobehavioral Sciences, Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA., Lopez IA; Cellular and Molecular Biology of the Inner Ear Laboratory, Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA., Brecha NC; Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Veterans Administration of Greater Los Angeles Health System, Los Angeles, CA 90073, USA; Departments of Medicine and Ophthalmology, Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA., Zipursky SL; Department of Biological Chemistry, Howard Hughes Medical Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA., Zeng H; Allen Institute for Brain Science, Seattle, WA 98109, USA., Dong HW; Center for Integrative Connectomics, University of Southern California Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, USC, Los Angeles, CA, 90033, USA; Zilkha Neurogenetic Institute, and Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA., Yang XW; Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, and Department of Psychiatry and Biobehavioral Sciences, Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: xwyang@mednet.ucla.edu.
Jazyk:	angličtina
Zdroj:	Neuron [Neuron] 2020 Oct 14; Vol. 108 (1), pp. 111-127.e6. Date of Electronic Publication: 2020 Aug 13.
DOI:	10.1016/j.neuron.2020.07.019
Abstrakt:	Cajal recognized that the elaborate shape of neurons is fundamental to their function in the brain. However, there are no simple and generalizable genetic methods to study neuronal or glial cell morphology in the mammalian brain. Here, we describe four mouse lines conferring Cre-dependent sparse cell labeling based on mononucleotide repeat frameshift (MORF) as a stochastic translational switch. Notably, the optimized MORF3 mice, with a membrane-bound multivalent immunoreporter, confer Cre-dependent sparse and bright labeling of thousands of neurons, astrocytes, or microglia in each brain, revealing their intricate morphologies. MORF3 mice are compatible with imaging in tissue-cleared thick brain sections and with immuno-EM. An analysis of 151 MORF3-labeled developing retinal horizontal cells reveals novel morphological cell clusters and axonal maturation patterns. Our study demonstrates a conceptually novel, simple, generalizable, and scalable mouse genetic solution to sparsely label and illuminate the morphology of genetically defined neurons and glia in the mammalian brain. Competing Interests: Declaration of Interests X.W.Y. and M.B.V. are co-inventors on a provisional patent related to this work. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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