Davis-Silberman, Noa and Kalich, Tomer and Oron-Karni, Varda and Marquardt, Till and Kroeber, Markus and Tamm, Ernst. R. and Ashery-Padan, Ruth (2005) Genetic dissection of Pax6 dosage requirements in the developing mouse eye. HUMAN MOLECULAR GENETICS, 14 (15). pp. 2265-2276. ISSN 0964-6906, 1460-2083
Full text not available from this repository. (Request a copy)Abstract
Haploinsufficiency of the transcription factor Pax6/PAX6 has been implicated in a number of congenital eye disorders in humans and mice, such as aniridia and Small-eye, which affect the development and function of the lens, cornea, anterior eye segment and neuroretina. However, the widespread distribution of Pax6/PAX6 protein within the developing and adult eye preclude the identification and direct study of the ocular tissues affected by a reduction in Pax6/PAX6 dosage. Here, we employed Cre/loxP-mediated inactivation of a single Pax6 allele in either the lens/cornea or the distal optic cup to dissect the tissue-specific sensitivity to Pax6 haploinsufficiency. Exclusive inactivation of a single Pax6 allele in the lens recapitulates the Small-eye lens and corneal defects, while only mildly affects iris morphology in a non-cell-autonomous fashion. Conversely, selective inactivation of a single Pax6 allele in the distal optic cup revealed primarily cell-autonomous dosage requirements for proper iris differentiation, with no affects on either lens or corneal morphology. Pax6 dosage within the distal optic cup is found here to influence the number of progenitors destined for the anterior ocular structures, the timing of iris muscle-cell differentiation and iris stroma development. Taken together, we genetically dissected the complex mouse Small-eye phenotype, thereby pinpointing the underlying Pax6/PAX6 haploinsufficiency to autonomous dosage requirements within the developing iris and lens/cornea tissues.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MIDBRAIN CREST CELLS; ANTERIOR SEGMENT; LENS DEVELOPMENT; TRANSGENIC MICE; CILIARY BODY; EXPRESSION; DIFFERENTIATION; MORPHOGENESIS; ABNORMALITIES; INDUCTION; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie > Prof. Dr. Ernst Tamm |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 May 2021 06:49 |
| Last Modified: | 03 May 2021 06:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/35804 |
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