title: NOVA regulates Dcc alternative splicing during neuronal migration and axon guidance in the spinal cord.
abstract: RNA-binding proteins (RBPs) control multiple aspects of post-transcriptional gene regulation and function during various biological processes in the nervous system. To further reveal the functional significance of RBPs during neural development, we carried out an in vivo RNAi screen in the dorsal spinal cord interneurons, including the commissural neurons. We found that the NOVA family of RBPs play a key role in neuronal migration, axon outgrowth, and axon guidance. Interestingly, Nova mutants display similar defects as the knockout of the Dcc transmembrane receptor. We show here that Nova deficiency disrupts the alternative splicing of Dcc, and that restoring Dcc splicing in Nova knockouts is able to rescue the defects. Together, our results demonstrate that the production of DCC splice variants controlled by NOVA has a crucial function during many stages of commissural neuron development.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, United States.
authors.forename: Janelle C
authors.initials: JC
authors.lastname: Leggere
authors.affiliation: Laboratory of Molecular Neuro-Oncology, Howard Hughes Medical Institute, The Rockefeller University, New York, United States.
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Laboratory of Molecular Neuro-Oncology, Howard Hughes Medical Institute, The Rockefeller University, New York, United States.
authors.forename: Robert B
authors.identifier: 0000-0002-5134-8088
authors.initials: RB
authors.lastname: Darnell
authors.affiliation: Laboratory of Brain Development and Repair, The Rockefeller University, New York, United States.
authors.forename: Marc
authors.initials: M
authors.lastname: Tessier-Lavigne
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, United States.
authors.forename: Harald J
authors.initials: HJ
authors.lastname: Junge
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, United States.
authors.forename: Zhe
authors.identifier: 0000-0003-0683-9491
authors.initials: Z
authors.lastname: Chen
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D000071437:Axon Guidance; D066294:Commissural Interneurons / Q000502:physiology*; D000075389:DCC Receptor / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005820:Genetic Testing; D051379:Mice; D018345:Mice, Knockout; D000090682:Neuro-Oncological Ventral Antigen; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000196:embryology*
chemical_list: D000951:Antigens, Neoplasm; D000075389:DCC Receptor; C501910:Dcc protein, mouse; D000090682:Neuro-Oncological Ventral Antigen; C000608219:Nova1 protein, mouse; C515624:Nova2 protein, mouse; D016601:RNA-Binding Proteins
keywords: DCC; NOVA; RNA binding proteins; alternative splicing; axon guidance; developmental biology; mouse; neuronal migration; neuroscience; stem cells