title: Neural differentiation modulates the vertebrate brain specific splicing program.
abstract: Alternative splicing patterns are known to vary between tissues but these patterns have been found to be predominantly peculiar to one species or another, implying only a limited function in fundamental neural biology. Here we used high-throughput RT-PCR to monitor the expression pattern of all the annotated simple alternative splicing events (ASEs) in the Reference Sequence Database, in different mouse tissues and identified 93 brain-specific events that shift from one isoform to another (switch-like) between brain and other tissues. Consistent with an important function, regulation of a core set of 9 conserved switch-like ASEs is highly conserved, as they have the same pattern of tissue-specific splicing in all vertebrates tested: human, mouse and zebrafish. Several of these ASEs are embedded within genes that encode proteins associated with the neuronal microtubule network, and show a dramatic and concerted shift within a short time window of human neural stem cell differentiation. Similarly these exons are dynamically regulated in zebrafish development. These data demonstrate that although alternative splicing patterns often vary between species, there is nonetheless a core set of vertebrate brain-specific ASEs that are conserved between species and associated with neural differentiation.
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle NE1 3BZ, United Kingdom.
authors.forename: Alicia
authors.initials: A
authors.lastname: Madgwick
authors.affiliation: Centre Nationale de la Recherche Scientifique, CRBM-UMR5237, Université de Montpellier, Montpellier, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Fort
authors.affiliation: Medical Toxicology Centre, Wolfson Building, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Hanson
authors.affiliation: Département de Microbiologie et d'Infectiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Québec, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Thibault
authors.affiliation: Institut de recherches cliniques de Montréal, Université de Montréal, Québec, Canada; Département de Microbiologie, Infectiologie, et Immunologie, Université de Montréal, Québec, Canada.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Gaudreau
authors.affiliation: Dynamique des Interactions Membranaires Normales et Pathologiques, UMR 5235 CNRS-Université de Montpellier, Montpellier, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Lutfalla
authors.affiliation: Institut de recherches cliniques de Montréal, Université de Montréal, Québec, Canada; Département de Microbiologie, Infectiologie, et Immunologie, Université de Montréal, Québec, Canada.
authors.forename: Tarik
authors.initials: T
authors.lastname: Möröy
authors.affiliation: Département de Microbiologie et d'Infectiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Québec, Canada.
authors.forename: Sherif
authors.initials: S
authors.lastname: Abou Elela
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle NE1 3BZ, United Kingdom.
authors.forename: Bill
authors.initials: B
authors.lastname: Chaudhry
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle NE1 3BZ, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Elliott
authors.affiliation: Medical Toxicology Centre, Wolfson Building, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Morris
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle NE1 3BZ, United Kingdom.
authors.forename: Julian P
authors.initials: JP
authors.lastname: Venables
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002454:Cell Differentiation; D006801:Humans; D051379:Mice; D009474:Neurons / Q000166:cytology*; D060888:Real-Time Polymerase Chain Reaction; D014714:Vertebrates / Q000378:metabolism*; D015027:Zebrafish