Bves Function in Corneal Development and Regeneration

描述（由申请人提供）：细胞粘附和运动在发育和成年角膜以及角膜再生中起关键作用。 在所有这些过程中，细胞粘附分子调节上皮细胞的生长、运动和稳定性。我们已经发现了一种新的细胞粘附分子（Bves），它在发育和成人眼睛的特定细胞群中表达，包括角膜上皮。 重要的是，我们的初步数据显示：1）Bves是在发育和再生上皮中运输到细胞/细胞接触点的第一种粘附分子之一，以及2）Byes功能的破坏抑制上皮形成和生长。这些新出现的数据导致我们的中心假设，即Bves在角膜上皮的生长，维持和再生中起着重要作用。为了验证这一假设，我们提出了以下具体目标：1。明确Bves在角膜发育过程中的时空表达模式; 2.明确Bves在角膜发育过程中的作用; 3.确定Bves在发育完全的角膜上皮中的功能。人角膜创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理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，以及在更大的意义上，眼睛中形态发生和伤口愈合的细胞和分子调节。

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.