Rybp, a polycomb complex-associated protein, is required for mouse eye development.
Rybp, a polycomb complex-associated protein, is required for mouse eye development.
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DOI：
10.1186/1471-213x-7-39
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发表时间：
2007-04-30
影响因子：
--
通讯作者：
Cvekl, Ales
中科院分区：
文献类型：
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作者：
Pirity, Melinda K.;Wang, Wei-Lin;Wolf, Louise V.;Tamm, Ernst R.;Schreiber-Agus, Nicole;Cvekl, Ales
Rybp（Ring1 和 YY1 结合蛋白）是一种锌指蛋白，可与哺乳动物多梳复合体的成员相互作用。之前我们已经证明 Rybp 对于早期胚胎发生至关重要，并且胚胎子集中 Rybp 单倍体不足会导致神经管闭合失败。在这里，我们使用四种体内小鼠模型研究了 Rybp 在眼部发育中的需求，这些模型导致 Rybp 的消融或过度表达。我们的结果表明，传统敲除小鼠中单个 Rybp 等位基因的缺失通常会导致视网膜缺损，即视裂的不完全闭合，其特征是 Pax6 的定位受到干扰，但 Pax2 的定位不受干扰。此外，大约一半的Rybp-/-<->Rybp+/+嵌合胚胎也出现了视网膜缺损和畸形晶状体。晶状体中 Rybp 的组织特异性转基因过度表达导致纤维细胞分化异常和严重的晶状体混浊，同时 AP-2α 和 Sox2 水平增加，βA4-晶状体蛋白基因表达水平降低。整个眼睛中普遍存在的 Rybp 转基因过度表达导致异常视网膜褶皱、角膜新生血管形成和晶状体混浊。其他变化包括前眼发育缺陷。这些研究确定 Rybp 是一种与缺损相关的新基因。与缺损相关的其他基因编码各种类型的转录因子，例如 BCOR、CBP、Chx10、Pax2、Pax6、Six3、Ski、Vax1 和 Vax2。我们认为 Rybp 在调节小鼠视网膜和晶状体发育中的多种功能是由这些基因和蛋白质之间的遗传、表观遗传和物理相互作用介导的。
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. 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.