| Description |
The eye originates from the prosencephalon, a region of the brain. Eye development studies may assist research in the central nervous system (CNS), since several CNS tissues (brain, spinal cord and eye etc.) exhibit similar gene expression profiles. In particular, homeobox genes have been shown to be crucial for patterning, specification and differentiation at tissue and cellular levels. Therefore, studying the function of single homeobox genes may be important for answering fundamental questions of developmental biology. In Chapter 1,1 review general eye structures and functions, and outline some genetic mutations causing anophthalmia (absence of eye) and microphthalmia (small eye). I focus on two developmental processes, patterning of optic vesicle and retinal histogenesis for this study. Moreover, molecular mechanisms are explored including the functions of homeobox genes involved in these two processes. Finally, the known functions of Lhx2 are introduced, which is crucial for eye development in several animal model systems. In Chapter 2,1 describe genetic inactivation experiments of Lhx2 and show that it plays important roles in optic vesicle patterning. Here, I tried to determine how Lhx2 inactivation causes anophthalmia and analyzed the expression patterns of both intrinsic and extrinsic factors crucial for optic vesicle patterning. I discovered that Lhx2 is required for optic vesicle patterning in both cell-autonomous and non-cell autonomous manners and surface ectoderm specification in a non-cell autonomous manner. In Chapter 3,1 describe experiments designed to test the function of Lhx2 in retinal progenitor cells by mating floxed Lhx2 mice with retinal specific ere line or inducible ere line. I discovered that Lhx2 is crucial for the maintenance of uncommitted progenitor cells, which have the potential to generate all cell types, by preventing cell cycle exit and differentiation. These studies also suggest that Lhx2 limits the acquisition of the biased progenitor state that has the capacity to generate only specific cell fates. In Chapter 4,1 summarize the diverse functions of Lhx2 during optic vesicle patterning and retinal histogenesis, and propose future studies that may help to elucidate molecular mechanisms mediated by Lhx2. |
