Regulation of rRNA synthesis in corneal epithelium

描述(由申请人提供)：我们的长期目标是了解 碱性核蛋白在角膜角质形成细胞rRNA转录中的作用。这 知识将有助于阐明调节细胞生长的机制。 角膜的增殖！上皮组织。几个转录因子已经被 被证明参与rRNA转录的调节。这些因素， 然而，rRNA合成的普遍存在和细胞类型的特异性调节因子是 人们对此仍知之甚少。Basonuclin，一种丰富的锌指蛋白 在复层上皮的角质形成细胞和睾丸生殖细胞中 卵巢，很可能是一种特定类型的细胞，与增殖有关 RRNA基因的转录调节因子，这是同类中的第一个。巴索努克林 在新生儿和成人角膜上皮细胞中检测到。 我们的假设是，Basonuclin是正常发育所必需的， 小鼠角膜上皮细胞的维护。Basonuclin增强rRNA 转录以满足角膜蛋白质合成的需要 角质形成细胞在发育和伤口愈合中的作用。以下三项 为了检验这一假设，我们提出了具体的目标： 特异靶1，探讨Basonuclin+/-ES细胞能否形成角膜 玫瑰花鼠嵌合体中的角质形成细胞。 具体目标2，检查细胞rRNA含量之间的相关性 以及在角膜和其他眼组织中是否存在碱性核蛋白 眼睛发育。 特异靶3，干扰通透性rRNA转录 角膜角质形成细胞的碱性核蛋白功能显性负性反应。

DESCRIPTION (provided by applicant):Our long-term goal is to understand the role of basonuclin in rRNA transcription in corneal keratinocytes. This knowledge will help the elucidation of the mechanisms that regulate the proliferation of cornea! epithelium. Several transcription factors have been shown to be involved in the regulation of rRNA transcription. These factors, however, are ubiquitous and cell-type specific regulators of rRNA synthesis are still poorly understood. Basonuclin, a zinc finger protein found in abundance in the keratinocytes of stratified epithelia and the germ cells of testis and ovary, is likely to be a cell type-specific, and proliferation-related transcriptional regulator for the rRNA genes, the first of its kind. Basonuclin was detected in the neonatal and adult corneal epithelium. Our hypothesis is that basonuclin is required for the normal development and maintenance of the mouse corneal epithelium. Basonuclin enhances rRNA transcription to fulfill the demand of protein synthesis in corneal keratinocytes during development and wound healing. The following three specific aims are proposed to test this hypothesis: Specific Aim 1, To investigate if basonuclin +/- ES cells can form corneal keratinocytes in ROSA mouse chimeras. Specific Aim 2, To examine the correlation between the cellular rRNA content and the presence of basonuclin in the cornea and other ocular tissues during eye development. Specific Aim 3, To interfere with the rRNA transcription in permeabilized corneal keratinocytes by dominant-negative reagents of basonuclin function.