Rybp, a polycomb complex-associated protein, is required for mouse eye development
1 Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
2 Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany
3 Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, NY 10461, USA
BMC Developmental Biology 2007, 7:39 doi:10.1186/1471-213X-7-39Published: 30 April 2007
Our results demonstrate that loss of a single Rybp allele in conventional knockout mice often resulted in retinal coloboma, an incomplete closure of the optic fissure, characterized by perturbed localization of Pax6 but not of Pax2. In addition, about one half of Rybp-/- <-> Rybp+/+ chimeric embryos also developed retinal colobomas and malformed lenses. Tissue-specific transgenic overexpression of Rybp in the lens resulted in abnormal fiber cell differentiation and severe lens opacification with increased levels of AP-2α and Sox2, and reduced levels of βA4-crystallin gene expression. Ubiquitous transgenic overexpression of Rybp in the entire eye caused abnormal retinal folds, corneal neovascularization, and lens opacification. Additional changes included defects in anterior eye development.
These studies establish Rybp as a novel gene that has been associated with coloboma. Other genes linked to coloboma encode various classes of transcription factors such as BCOR, CBP, Chx10, Pax2, Pax6, Six3, Ski, Vax1 and Vax2. We propose that the multiple functions for Rybp in regulating mouse retinal and lens development are mediated by genetic, epigenetic and physical interactions between these genes and proteins.