title: Dcc regulates asymmetric outgrowth of forebrain neurons in zebrafish.
abstract: The guidance receptor DCC (deleted in colorectal cancer) ortholog UNC-40 regulates neuronal asymmetry development in Caenorhabditis elegans, but it is not known whether DCC plays a role in the specification of neuronal polarity in vertebrates. To examine the roles of DCC in neuronal asymmetry regulation in vertebrates, we studied zebrafish anterior dorsal telencephalon (ADt) neuronal axons. We generated transgenic zebrafish animals expressing the photo-convertible fluorescent protein Kaede in ADt neurons and then photo-converted Kaede to label specifically the ADt neuron axons. We found that ADt axons normally project ventrally. Knock down of Dcc function by injecting antisense morpholino oligonucleotides caused the ADt neurons to project axons dorsally. To examine the axon projection pattern of individual ADt neurons, we labeled single ADt neurons using a forebrain-specific promoter to drive fluorescent protein expression. We found that individual ADt neurons projected axons dorsally or formed multiple processes after morpholino knock down of Dcc function. We further found that knock down of the Dcc ligand, Netrin1, also caused ADt neurons to project axons dorsally. Knockdown of Neogenin1, a guidance receptor closely related to Dcc, enhanced the formation of aberrant dorsal axons in embryos injected with Dcc morpholino. These experiments provide the first evidence that Dcc regulates polarized axon initiation and asymmetric outgrowth of forebrain neurons in vertebrates.
authors.affiliation: Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors.forename: Jingxia
authors.initials: J
authors.lastname: Gao
authors.forename: Changwen
authors.initials: C
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Liu
authors.initials: L
authors.lastname: Sun
authors.forename: Cuizhen
authors.initials: C
authors.lastname: Zhang
authors.forename: Monte
authors.initials: M
authors.lastname: Westerfield
authors.forename: Gang
authors.initials: G
authors.lastname: Peng
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D001483:Base Sequence; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D000075389:DCC Receptor; D017931:DNA Primers / Q000235:genetics; D055785:Gene Knockdown Techniques; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D000075388:Netrin-1; D009474:Neurons / Q000166:cytology; D016548:Prosencephalon / Q000166:cytology / Q000196:embryology*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
chemical_list: D000075389:DCC Receptor; D017931:DNA Primers; C513582:Kaede protein, Trachyphyllia geoffroyi; D060850:LIM-Homeodomain Proteins; C514539:Lhx5 protein, zebrafish; D008164:Luminescent Proteins; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D029961:Zebrafish Proteins; C506552:dcc protein, zebrafish; C091279:neogenin; D000075388:Netrin-1