title: Rybp, a polycomb complex-associated protein, is required for mouse eye development.
abstract: BACKGROUND
  Rybp (Ring1 and YY1 binding protein) is a zinc finger protein which interacts with the members of the mammalian polycomb complexes. Previously we have shown that Rybp is critical for early embryogenesis and that haploinsufficiency of Rybp in a subset of embryos causes failure of neural tube closure. Here we investigated the requirement for Rybp in ocular development using four in vivo mouse models which resulted in either the ablation or overexpression of Rybp.
  
  
  RESULTS
  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-2alpha and Sox2, and reduced levels of betaA4-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA. mpirity@gmail.com <mpirity@gmail.com>
authors.forename: Melinda K
authors.initials: MK
authors.lastname: Pirity
authors.forename: Wei-Lin
authors.initials: WL
authors.lastname: Wang
authors.forename: Louise V
authors.initials: LV
authors.lastname: Wolf
authors.forename: Ernst R
authors.initials: ER
authors.lastname: Tamm
authors.forename: Nicole
authors.initials: N
authors.lastname: Schreiber-Agus
authors.forename: Ales
authors.initials: A
authors.lastname: Cvekl
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003103:Coloboma / Q000196:embryology / Q000235:genetics; D003315:Cornea / Q000002:abnormalities / Q000196:embryology / Q000648:ultrastructure; D004622:Embryo, Mammalian; D005123:Eye / Q000196:embryology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007908:Lens, Crystalline / Q000002:abnormalities / Q000196:embryology / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D011247:Pregnancy; D012097:Repressor Proteins / Q000235:genetics*; D012160:Retina / Q000002:abnormalities / Q000196:embryology / Q000648:ultrastructure; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D012097:Repressor Proteins; C120616:Rybp protein, mouse