title: The Pax6 isoform bearing an alternative spliced exon promotes the development of the neural retinal structure.
abstract: The vertebrate retina has an area where visual cells are closely packed for proper vision that is known as a fovea, an area centralis or a visual streak. The molecular mechanism that regulates the formation of these structures and visual cell gradients is unknown. The transcription factor Pax6 is a master regulator of eye development. A Pax6 isoform that contains an exon 5a-encoded 14 amino acid insertion in its paired domain, Pax6(+5a), has different DNA-binding properties compared with the Pax6(-5a) isoform. Little is known about the functional significance of Pax6(+5a). Here, we show that Pax6(+5a) is expressed especially in the retinal portion where visual cells accumulate during eye development and, when overexpressed, induces a remarkable well-differentiated retina-like structure. Pax6(+5a) proteins that bear point mutations that are found in patients with foveal hypoplasia are unable to induce these ectopic retina-like structures. We propose that Pax6(+5a) induces a developmental cascade in the prospective fovea, area centralis or visual streak region that leads to the formation of a retinal architecture bearing densely packed visual cells.
authors.affiliation: Department of Ophthalmology, National Center for Child Health and Developent, Tokyo, Japan. azuma-n@ncchd.go.jp
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Azuma
authors.forename: Keiko
authors.initials: K
authors.lastname: Tadokoro
authors.forename: Astuko
authors.initials: A
authors.lastname: Asaka
authors.forename: Masao
authors.initials: M
authors.lastname: Yamada
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Handa
authors.forename: Satsuki
authors.initials: S
authors.lastname: Matsushima
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kohsaka
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kida
authors.forename: Tomoki
authors.initials: T
authors.lastname: Shiraishi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ogura
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimamura
authors.forename: Masato
authors.initials: M
authors.lastname: Nakafuku
mesh_terms: D017398:Alternative Splicing / Q000502:physiology*; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002642:Chick Embryo; D002645:Chickens; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000096:biosynthesis* / Q000235:genetics; D005584:Fovea Centralis / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D017354:Point Mutation; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D020033:Protein Isoforms; D012097:Repressor Proteins