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Here, we show that neutralization of neuronal Nogo-A or Nogo-A gene ablation (KO) leads to longer neurites, increased fasciculation, and decreased branching of cultured dorsal root ganglion neurons. The same effects are seen with antibodies against the Nogo receptor complex components NgR and Lingo1, or by blocking the downstream effector Rho kinase (ROCK). In the chicken embryo, in ovo injection of anti-Nogo-A antibodies leads to aberrant innervation of the hindlimb. Genetic ablation of Nogo-A causes increased fasciculation and reduced branching of peripheral nerves in Nogo-A KO mouse embryos. Thus, Nogo-A is a developmental neurite growth regulatory factor with a role as a negative regulator of axon-axon adhesion and growth, and as a facilitator of neurite branching.<\/jats:p>","DOI":"10.1242\/dev.048371","type":"journal-article","created":{"date-parts":[[2010,6,24]],"date-time":"2010-06-24T00:59:18Z","timestamp":1277341158000},"page":"2539-2550","source":"Crossref","is-referenced-by-count":79,"title":["Neuronal Nogo-A regulates neurite fasciculation, branching and extension in the developing nervous system"],"prefix":"10.1242","volume":"137","author":[{"given":"Marija M.","family":"Petrinovic","sequence":"first","affiliation":[{"name":"Brain Research Institute, University of Zurich and Department of Biology, ETH Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carri S.","family":"Duncan","sequence":"additional","affiliation":[{"name":"Brain Research Institute, University of Zurich and Department of Biology, ETH Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitris","family":"Bourikas","sequence":"additional","affiliation":[{"name":"Institute of Zoology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Weinman","sequence":"additional","affiliation":[{"name":"Brain Research Institute, University of Zurich and Department of Biology, ETH Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Montani","sequence":"additional","affiliation":[{"name":"Brain Research Institute, University of Zurich and Department of Biology, ETH Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aileen","family":"Schroeter","sequence":"additional","affiliation":[{"name":"Brain Research Institute, University of Zurich and Department of Biology, ETH Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Maerki","sequence":"additional","affiliation":[{"name":"Cell and Developmental Biology, Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Sommer","sequence":"additional","affiliation":[{"name":"Cell and Developmental Biology, Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther T.","family":"Stoeckli","sequence":"additional","affiliation":[{"name":"Institute of Zoology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin E.","family":"Schwab","sequence":"additional","affiliation":[{"name":"Brain Research Institute, University of Zurich and Department of Biology, ETH Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042606032545700_R1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s11068-007-9014-3","article-title":"Synaptic destabilization by neuronal Nogo-A","volume":"35","author":"Aloy","year":"2006","journal-title":"Brain Cell Biol."},{"key":"2021042606032545700_R2","doi-asserted-by":"crossref","first-page":"pe24","DOI":"10.1126\/stke.2352004pe24","article-title":"From cell death to neuronal regeneration, effects of the p75 neurotrophin receptor depend on interactions with partner subunits","volume":"2004","author":"Bandtlow","year":"2004","journal-title":"Sci. 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Neurobiol."},{"key":"2021042606032545700_R41","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0896-6273(03)00226-5","article-title":"Systemic deletion of the myelin-associated outgrowth inhibitor Nogo-A improves regenerative and plastic responses after spinal cord injury","volume":"38","author":"Simonen","year":"2003","journal-title":"Neuron"},{"key":"2021042606032545700_R42","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/0896-6273(92)90125-W","article-title":"Polysialic acid influences specific pathfinding by avian motoneurons","volume":"8","author":"Tang","year":"1992","journal-title":"Neuron"},{"key":"2021042606032545700_R43","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/0896-6273(94)90356-5","article-title":"Polysialic acid regulates growth cone behavior during sorting of motor axons in the plexus region","volume":"13","author":"Tang","year":"1994","journal-title":"Neuron"},{"key":"2021042606032545700_R44","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0012-1606(85)90360-4","article-title":"Development of the major pathways for neurite outgrowth in the chick hindlimb","volume":"109","author":"Tosney","year":"1985","journal-title":"Dev. 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