title: Human NDE1 splicing and mammalian brain development.
abstract: Exploring genetic and molecular differences between humans and other close species may be the key to explain the uniqueness of our brain and the selective pressures under which it evolves. Recent discoveries unveiled the involvement of Nuclear distribution factor E-homolog 1 (NDE1) in human cerebral cortical neurogenesis and suggested a role in brain evolution; however the evolutionary changes involved have not been investigated. NDE1 has a different gene structure in human and mouse resulting in the production of diverse splicing isoforms. In particular, mouse uses the terminal exon 8 T, while Human uses terminal exon 9, which is absent in rodents. Through chimeric minigenes splicing assay we investigated the unique elements regulating NDE1 terminal exon choice. We found that selection of the terminal exon is regulated in a cell dependent manner and relies on gain/loss of splicing regulatory sequences across the exons. Our results show how evolutionary changes in cis as well as trans acting signals have played a fundamental role in determining NDE1 species specific splicing isoforms supporting the notion that alternative splicing plays a central role in human genome evolution, and possibly human cognitive predominance.
authors.affiliation: Human Development and Health, Faculty of Medicine, University of Southampton, UK.
authors.forename: S
authors.initials: S
authors.lastname: Mosca
authors.affiliation: Human Development and Health, Faculty of Medicine, University of Southampton, UK.
authors.forename: M
authors.initials: M
authors.lastname: Raponi
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, UK.
authors.forename: A
authors.initials: A
authors.lastname: Meneghello
authors.affiliation: International Centre of Genetic Engineering and Biotechnology, Trieste, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Buratti
authors.affiliation: Cambridge Institute of Medical Research, University of Cambridge, Cambridge, UK.
authors.forename: C G
authors.initials: CG
authors.lastname: Woods
authors.affiliation: Human Development and Health, Faculty of Medicine, University of Southampton, UK.
authors.forename: D
authors.initials: D
authors.lastname: Baralle
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology* / Q000502:physiology*; D005091:Exons; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D012326:RNA Splicing; D012045:Regulatory Sequences, Nucleic Acid
chemical_list: D008869:Microtubule-Associated Proteins; C525094:Nde1 protein, human