Bves Function in Corneal Development and Regeneration

Bves 在角膜发育和再生中的功能

• 批准号: 7024985
• 负责人: David M BADER
• 金额: $ 14.75万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7024985
• 关键词: cell adhesion molecules; chick embryo; chickens; cornea; corneal epithelium; eye regeneration; gene expression; histogenesis; laboratory mouse; protein structure function; tissue /cell culture; transfection; wound healing

DESCRIPTION (provided by applicant): Cell adhesion and movement play critical roles in the developing and adult cornea as well as in corneal regeneration. In all these processes, cell adhesion molecules regulate epithelial growth, movement, and stability. We have discovered a new cell adhesion molecule (Bves) that is expressed in specific cell populations of the developing and adult eye, including the corneal epithelium. Importantly, our preliminary data show: 1) Bves is one of the first adhesion molecules that traffics to points of cell/cell contact in developing and regenerating epithelia and 2) that disruption of Byes function inhibits epithelial formation and outgrowth. These emerging data lead to our central hypothesis that Bves plays an important role in the growth, maintenance and regeneration of corneal epithelium. To test this hypothesis, we propose the following specific aims: 1. To determine the precise temporal and spatial expression patterns of Bves during corneal development; 2. To determine the function of Bves during corneal development and; 3. To determine the function of Bves in the fully developed corneal epithelium. In vitro models of human corneal wounding will be used to determine cellular function of Bves in repair. While cell movement during development, renewal and regeneration is critical to corneal function, the underlying molecular mechanisms governing these processes are not known. As Bves is a regulator of cell adhesion and epithelial morphogenesis, elucidating its role in corneal development and homeostasis is an important step in understanding corneal biology. Our proposed studies will determine the role of Bves in the cornea and, in a larger sense, the cellular and molecular regulation of morphogenesis and wound healing in the eye.

描述（由申请人提供）：细胞粘附和运动在角膜的发育和成年以及角膜再生中发挥着关键作用。 在所有这些过程中，细胞粘附分子调节上皮生长、运动和稳定性。我们发现了一种新的细胞粘附分子 (Bves)，它在发育中和成年眼睛的特定细胞群（包括角膜上皮）中表达。 重要的是，我们的初步数据显示：1) Bves 是第一个在上皮细胞发育和再生过程中运输至细胞/细胞接触点的粘附分子之一，2) Byes 功能的破坏会抑制上皮细胞的形成和生长。这些新出现的数据引出了我们的中心假设：Bves 在角膜上皮的生长、维护和再生中发挥着重要作用。为了检验这一假设，我们提出以下具体目标： 1. 确定角膜发育过程中 Bves 的精确时空表达模式； 2. 确定 Bves 在角膜发育过程中的功能； 3.确定Bves在完全发育的角膜上皮中的功能。人类角膜损伤的体外模型将用于确定 Bves 在修复中的细胞功能。 当细胞在发育过程中运动时， 更新和再生对于角膜功能至关重要，但控制这些过程的潜在分子机制尚不清楚。 由于 Bves 是细胞粘附和上皮形态发生的调节剂，阐明其在角膜发育和稳态中的作用是了解角膜生物学的重要一步。 我们提出的研究将确定 Bves 在角膜中的作用，从更广泛的意义上讲，确定眼睛形态发生和伤口愈合的细胞和分子调节。