We propose to study the role of Gremlin, a Bone Morphogenetic Protein (BMP) antagonist, in the development of the eye, in Xenopus laevìs, a well-established model system for studying vertebrate embryogenesis. BMP signalling pathways are known to regulate cell proliferation, differentiation and programmed cell death. It is known that the temporal and spatial patterns of BMPs and their antagonists in the developing vertebrate control the patterning of tissues and organogenesis. Previous work in our laboratory has shown that gremlin is expressed in the developing kidney and eye and that over-expression of gremlin results in enlarged eyes and kidneys.
The main aim of my research will be to further investigate the role of gremlin in the development of the eye. We propose to thoroughly characterize the expression of gremlin in the developing eye in various stages of development and compare this to the expression of BMPs and other genes known to be involved in eye development. In addition to characterizing the enlarged eye phenotype already produced in our laboratory, we propose to use further over-expression and knockdown studies designed to direct mis-expression of gremlin to the developing eye. Morphological affects of gremlin mis-expression will be assessed by histological analysis of sections and with the use of known cell-type specific markers. Analysis of the expression of other key regulators of eye development will help determine the place of gremlin in the developmental pathway. Since gremlin has been demonstrated to have a r ole in regulating apoptosis and cell proliferation, we will determine whether gremlin expression correlates with areas of apoptosis or cell proliferation in the developing eye. We will determine whether the morphological changes caused by gremlin mis-expression are due to mis-regulation of one of these processes.
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