DESCRIPTION (provided by applicant): The overall goal of this proposal is to identify novel genes and associated pathways involved in the development of the anterior segment. Genetic studies have contributed a great deal to our current understanding of the developmental processes as well as associated genes and pathways during the ocular development. However, many genes as well as molecular mechanisms are still unclear. To aid in the discovery of the gene/pathway/mechanism associated with anterior segment development, phenotype driven approaches have been utilized extensively. This proposal focuses on the woe and woe2 mouse models. Both woe and woe2 are autosomal recessive loci that exhibit the eyelid open at birth (EOB) phenotype, microphthalmia/anopthalmia, cataracts and defects in the anterior segment structures originating from the neural crest (NC) cells. The woe2 mice unlike woe exhibit optic nerve hypoplasia. Both mice exhibit the wavy fur phenotype. Based on the phenotypic similarities, we hypothesized that woe and woe2 genes play a role in overlapping molecular pathways essential for ocular development. By applying the positional cloning strategies we identified genes and mutations responsible for woe and woe2. The woe mice carry a hypomorphic mutation in the Adam17 gene whereas the woe2 mice carry a deletion in the Ppp1r13l gene. The goal of this proposal is to understand the role of Adam17 and Ppp1r13l during the eye development. The Specific Aim 1 focuses on evaluation of Adam17 role during the embryonic eyelid closure, development of NC-derived anterior structures and a role of Adam17 during corneal wound healing. The Specific Aim2 focuses on evaluation of the role of Ppp1r13l during embryonic eyelid closure, anterior segment development and the role of Ppp1r13l during optic nerve development. This approach will provide novel information about the functions of Adam17 and Ppp1r13l and the associated pathways during anterior segment development. PUBLIC HEALTH RELEVANCE: This proposal focuses on the identification of novel regulatory genes and the pathways governing the anterior segment development. In order to better understand the etiology of common anterior segment eye diseases such as cataracts and glaucoma, it is essential that we gain a better understanding about the mechanisms that play a central role during development.

Principal Investigator: Sidjanin, D.J. This proposal focuses on the identification of novel regulatory genes and the pathways governing the anterior segment development. In order to better understand the etiology of common anterior segment eye diseases such as cataracts and glaucoma, it is essential that we gain a better understanding about the mechanisms that play a central role during development.