title: Vesicular stomatitis virus enables gene transfer and transsynaptic tracing in a wide range of organisms.
abstract: Current limitations in technology have prevented an extensive analysis of the connections among neurons, particularly within nonmammalian organisms. We developed a transsynaptic viral tracer originally for use in mice, and then tested its utility in a broader range of organisms. By engineering the vesicular stomatitis virus (VSV) to encode a fluorophore and either the rabies virus glycoprotein (RABV-G) or its own glycoprotein (VSV-G), we created viruses that can transsynaptically label neuronal circuits in either the retrograde or anterograde direction, respectively. The vectors were investigated for their utility as polysynaptic tracers of chicken and zebrafish visual pathways. They showed patterns of connectivity consistent with previously characterized visual system connections, and revealed several potentially novel connections. Further, these vectors were shown to infect neurons in several other vertebrates, including Old and New World monkeys, seahorses, axolotls, and Xenopus. They were also shown to infect two invertebrates, Drosophila melanogaster, and the box jellyfish, Tripedalia cystophora, a species previously intractable for gene transfer, although no clear evidence of transsynaptic spread was observed in these species. These vectors provide a starting point for transsynaptic tracing in most vertebrates, and are also excellent candidates for gene transfer in organisms that have been refractory to other methods.
authors: Department of Genetics, Harvard Medical School, Boston, Massachusetts, 02115.|Department of Ophthalmology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, 02115.
authors: Nathan A
authors: NA
authors: Mundell
authors: Department of Genetics, Harvard Medical School, Boston, Massachusetts, 02115.|Department of Ophthalmology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, 02115.
authors: Kevin T
authors: KT
authors: Beier
authors: Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, Massachusetts, 01238.
authors: Y Albert
authors: YA
authors: Pan
authors: Department of Genetics, Harvard Medical School, Boston, Massachusetts, 02115.|Department of Ophthalmology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, 02115.
authors: Sylvain W
authors: SW
authors: Lapan
authors: Department of Genetics, Harvard Medical School, Boston, Massachusetts, 02115.|Department of Ophthalmology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, 02115.
authors: Didem
authors: D
authors: Göz Aytürk
authors: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, 02115.
authors: Vladimir K
authors: VK
authors: Berezovskii
authors: Department of Genetics, Harvard Medical School, Boston, Massachusetts, 02115.
authors: Abigail R
authors: AR
authors: Wark
authors: Department of Genetics, Harvard Medical School, Boston, Massachusetts, 02115.|Department of Ophthalmology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, 02115.
authors: Eugene
authors: E
authors: Drokhlyansky
authors: Department of Ecology, Evolution and Marine Biology, University of California, Santa Barbara, Santa Barbara, California, 93106.
authors: Jan
authors: J
authors: Bielecki
authors: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, 02115.
authors: Richard T
authors: RT
authors: Born
authors: Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, Massachusetts, 01238.
authors: Alexander F
authors: AF
authors: Schier
authors: Department of Genetics, Harvard Medical School, Boston, Massachusetts, 02115.|Department of Ophthalmology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, 02115.
authors: Constance L
authors: CL
authors: Cepko
mesh_terms: D000818:Animals; D002460:Cell Line / Q000166:cytology / Q000378:metabolism; D018014:Gene Transfer Techniques; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007448:Invertebrates / Q000033:anatomy & histology / Q000378:metabolism; D056347:Neuroanatomical Tract-Tracing Techniques; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011820:Rabies virus / Q000235:genetics; D014714:Vertebrates / Q000033:anatomy & histology / Q000378:metabolism; D054243:Vesicular Stomatitis; D018116:Vesiculovirus / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014795:Visual Pathways / Q000033:anatomy & histology / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D014764:Viral Proteins
keywords: AB_10562207; AB_531908; AB_591819; RRID: AB_10053281; SciRes_000161; VSV; anterograde; centrifugal; in vivo; polysynaptic; retina; retrograde; transsynaptic; visual pathways