title: Possible involvement of SINEs in mammalian-specific brain formation.
abstract: Retroposons, such as short interspersed elements (SINEs) and long interspersed elements (LINEs), are the major constituents of higher vertebrate genomes. Although there are many examples of retroposons' acquiring function, none has been implicated in the morphological innovations specific to a certain taxonomic group. We previously characterized a SINE family, AmnSINE1, members of which constitute a part of conserved noncoding elements (CNEs) in mammalian genomes. We proposed that this family acquired genomic functionality or was exapted after retropositioning in a mammalian ancestor. Here we identified 53 new AmnSINE1 loci and refined 124 total loci, two of which were further analyzed. Using a mouse enhancer assay, we demonstrate that one SINE locus, AS071, 178 kbp from the gene FGF8 (fibroblast growth factor 8), is an enhancer that recapitulates FGF8 expression in two regions of the developing forebrain, namely the diencephalon and the hypothalamus. Our gain-of-function analysis revealed that FGF8 expression in the diencephalon controls patterning of thalamic nuclei, which act as a relay center of the neocortex, suggesting a role for FGF8 in mammalian-specific forebrain patterning. Furthermore, we demonstrated that the locus, AS021, 392 kbp from the gene SATB2, controls gene expression in the lateral telencephalon, which is thought to be a signaling center during development. These results suggest important roles for SINEs in the development of the mammalian neuronal network, a part of which was initiated with the exaptation of AmnSINE1 in a common mammalian ancestor.
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-21 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Hidenori
authors.initials: H
authors.lastname: Nishihara
authors.forename: Mika
authors.initials: M
authors.lastname: Hirakawa
authors.forename: Koji
authors.initials: K
authors.lastname: Fujimura
authors.forename: Mikiko
authors.initials: M
authors.lastname: Tanaka
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kokubo
authors.forename: Chiharu
authors.initials: C
authors.lastname: Kimura-Yoshida
authors.forename: Isao
authors.initials: I
authors.lastname: Matsuo
authors.forename: Kenta
authors.initials: K
authors.lastname: Sumiyama
authors.forename: Naruya
authors.initials: N
authors.lastname: Saitou
authors.forename: Tomomi
authors.initials: T
authors.lastname: Shimogori
authors.forename: Norihiro
authors.initials: N
authors.lastname: Okada
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D002642:Chick Embryo; D002877:Chromosomes, Human / Q000235:genetics; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008322:Mammals / Q000196:embryology / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010802:Phylogeny; D020086:Short Interspersed Nucleotide Elements
chemical_list: D051524:Fibroblast Growth Factor 8