Integrated signaling is critical both during retinal development and in maintenance of mature neurons. Using zebrafish, we have developed a series of transgenic and mutant tools to probe the regulation and relationships between two pathways important for normal retinal development, Notch and Hippo-Yap/Taz. We will investigate how individual cellular processes, particularly endocytosis and endomembrane trafficking, shape these pathways. Attention will be placed on components of each pathway as well a Crumbs, which has been shown to tune both Notch and Hippo-Yap/Taz. In addition to assessing the nuances of pathway regulation, we will also test the precise function of each signaling module on retinogenesis. Last, we address the function of Crumbs mediated Hippo-Yap/Taz-Tead signaling in photoreceptor homeostasis. The proposed experiments address basic cellular questions on the nature of Notch and Hippo/Yap signaling. This research, therefore, has implications for improving stem cell manipulation and a better defining targets for slowing or preventing photoreceptor degenerations. !

Public Health Relevance

During both retinal development and in the maintenance of mature retinal neurons such as photoreceptor cells, various signaling pathways must be precisely regulated. In this proposal we describe studies primarily in zebrafish to understand the relationships between two signaling modules implicated both during development and in tissue homeostasis.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Special Emphasis Panel (BVS)
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Greenwell, Thomas
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Medical College of Wisconsin
Anatomy/Cell Biology
Schools of Medicine
United States
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Miesfeld, Joel B; Gestri, Gaia; Clark, Brian S et al. (2015) Yap and Taz regulate retinal pigment epithelial cell fate. Development 142:3021-32
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Insinna, Christine; Baye, Lisa M; Amsterdam, Adam et al. (2010) Analysis of a zebrafish dync1h1 mutant reveals multiple functions for cytoplasmic dynein 1 during retinal photoreceptor development. Neural Dev 5:12

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