Brainwide Genetic Sparse Cell Labeling to Illuminate the Morphology of Neurons and Glia with Cre-Dependent MORF Mice. Neuron 2020 Oct 14;108(1):111-127.e6
Date
08/17/2020Pubmed ID
32795398Pubmed Central ID
PMC7572760DOI
10.1016/j.neuron.2020.07.019Scopus ID
2-s2.0-85090058615 (requires institutional sign-in at Scopus site) 25 CitationsAbstract
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.
Author List
Veldman MB, Park CS, Eyermann CM, Zhang JY, Zuniga-Sanchez E, Hirano AA, Daigle TL, Foster NN, Zhu M, Langfelder P, Lopez IA, Brecha NC, Zipursky SL, Zeng H, Dong HW, Yang XWAuthor
Matthew B. Veldman PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAstrocytes
Brain
Frameshift Mutation
Green Fluorescent Proteins
Integrases
Mice
Mice, Transgenic
Microglia
Microsatellite Repeats
Neurons
Retinal Horizontal Cells
