Davis, Noa and Yoffe, Chen and Raviv, Shaul and Antes, Ran and Berger, Joachim and Holzmann, Silvia and Stoykova, Anastassia and Overbeek, Paul A. and Tamm, Ernst R. and Ashery-Padan, Ruth (2009) Pax6 dosage requirements in iris and ciliary body differentiation. DEVELOPMENTAL BIOLOGY, 333 (1). pp. 132-142. ISSN 0012-1606, 1095-564X
Full text not available from this repository. (Request a copy)Abstract
Pax6 is a highly conserved transcription factor that controls the morphogenesis of various organs. Changes in Pax6 dosage have been shown to affect the formation of multiple tissues. PAX6 haploinsufficiency leads to aniridia, a pan-ocular disease primarily characterized by iris hypoplasia. Herein, we employ a modular system that includes null and overexpressed conditional alleles of Pax6. The use of the Tyrp2-Cre line, active in iris and ciliary body (CB) primordium, enabled us to investigate the effect of varying dosages of Pax6 on the development of these ocular sub-organs. Our findings show that a lack of Pax6 in these regions leads to dysgenesis of the iris and CB, while heterozygosity impedes growth of the iris and maturation of the iris sphincter. Overexpression of the canonical, but not the alternative splice variant of Pax6 results in severe structural aberrations of the CB and hyperplasia of the iris sphincter. A splice variant-specific rescue experiment revealed that both splice variants are able to correct iris hypoplasia, while only the canonical form rescues the sphincter. Overall, these findings demonstrate the dosage-sensitive roles of Pax6 in the formation of both the CB and the iris. (C) 2009 Elsevier Inc. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COMPLEX MATERNAL REARRANGEMENT; RETINAL PIGMENTED EPITHELIUM; PARTIAL TRISOMY; EYE DEVELOPMENT; PAIRED DOMAIN; PROGENITOR CELLS; SMOOTH-MUSCLE; NEURAL RETINA; GENE; LENS; Pax6; Pax6-5a; Alternative splicing; Gene dosage; Eye; Iris; Sphincter muscle; Ciliary body; Cre/loxP |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Biology, Preclinical Medicine > Institut für Anatomie Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie > Prof. Dr. Ernst Tamm |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Sep 2020 04:46 |
| Last Modified: | 08 Sep 2020 04:46 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28436 |
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