Gene expression in lens fiber cell differentiation

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DESCRIPTION: (Applicant's Abstract) The mammalian lens is a relatively simple organ composed of terminally differentiated and amitotic lens fiber cells capped on the anterior surface by a layer of immature, mitotic epithelial cells. Development of the lens can be divided into two stages. The first stage results in the formation of the lens vesicle and the second stage involves growth and differentiation of the lens vesicle. The lens vesicle is derived from the head ectoderm in a region called lens placode. Under the induction of optic vesicle (the future retina), the lens placode invaginates and eventually pinches off the head ectoderm to form a single cell layered sphere, the lens vesicle. Cells in the posterior portion (those facing optic vesicle or retina) of the lens vesicle differentiate into primary lens fiber cells. The anterior portion of the lens vesicle remains as an undifferentiated epithelium. At the second stage of lens development, the epithelial cells continue to proliferate in a region slightly anterior to the lens equator and the progeny of these proliferative epithelial cells differentiate into lens fiber cells (secondary lens fiber cells) at the equator (bow region). Formation of lens fiber cells from lens epithelial cells involves dramatic changes in cell size and shape. How do these changes occur? Obviously, they are genetically controlled. It very important for us to understand the genetic program that underlies these dramatic changes. Alterations in gene expression are ultimately responsible for these changes. Our aim is to identify those genes whose expression is altered during, the formation of lens fiber cells, by taking advantage of mouse genetic models that fail to from lens fiber cells properly. Identification of these genes may provide clinical targets for treatment of lens related vision impairment, such as cataracts.