The Pax6 isoform bearing an alternative spliced exon promotes the development of the neural retinal structure.
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.
Azuma
Noriyuki
N
Department of Ophthalmology, National Center for Child Health and Developent, Tokyo, Japan. azuma-n@ncchd.go.jp
Tadokoro
Keiko
K
Asaka
Astuko
A
Yamada
Masao
M
Yamaguchi
Yuki
Y
Handa
Hiroshi
H
Matsushima
Satsuki
S
Watanabe
Takashi
T
Kohsaka
Shinichi
S
Kida
Yasuyuki
Y
Shiraishi
Tomoki
T
Ogura
Toshihiko
T
Shimamura
Kenji
K
Nakafuku
Masato
M
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
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