Patterning is a fundamental process that allows tissues to develop complexity through the use of relatively simple 'rules'. To explore these rules and understand how epithelia assemble into useful tissues, my laboratory has focused on the developing Drosophila pupil eye. The fly eye is a relatively simple neuroepithelium composed of several hundred 'ommatidia'(visual units) precisely arranged in a hexagonal array across the eye field. This precise pattern is required to re-create a coherent visual field. Patterning of the ommatidial array is achieved by precise arrangement of interommatidial precursor cells. These IPCs are glial-like support cells;movement within the epithelium coupled with selective cell death re-arranges them into an interweaving hexagonal lattice. This process requires several surface factors including Drosophila orthologs of heterophilic adhesion molecules of the Nephrin super family and E-Cadherin. Notch, Wingless, and Dpp pathways provide local signaling. In this proposal, we extend our understanding of these surface events to the Drosophila EGF-Receptor. Further, we connect surface events to intracellular signaling, which in turn leads to dynamic remodeling of the Actin cytoskeleton. Pathways include the fly CD2AP/CIN85 ortholog Cindr and the ZO-1 ortholog Pyd. We extend this work to include new regulators of the Actin cytoskeleton, with an emphasis on their ability to mediate the dynamic cytoskeletal re-arrangements necessary for a cell to respond to extracellular signals and move into its correct niche.

Public Health Relevance

Directed cell movement is a key step in assembly of neuroepithelia such as the developing retina. This Proposal explored the mechanisms that guide specific cell types into the niches required to assemble a functional eye.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Biology and Diseases of the Posterior Eye Study Section (BDPE)
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Neuhold, Lisa
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Icahn School of Medicine at Mount Sinai
Schools of Medicine
New York
United States
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Rudrapatna, V A; Bangi, E; Cagan, R L (2014) A Jnk-Rho-Actin remodeling positive feedback network directs Src-driven invasion. Oncogene 33:2801-6
Rudrapatna, Vivek A; Bangi, Erdem; Cagan, Ross L (2013) Caspase signalling in the absence of apoptosis drives Jnk-dependent invasion. EMBO Rep 14:172-7
Cagan, Ross L (2011) The Drosophila nephrocyte. Curr Opin Nephrol Hypertens 20:409-15
Bao, Sujin; Fischbach, Karl-Friedrich; Corbin, Victoria et al. (2010) Preferential adhesion maintains separation of ommatidia in the Drosophila eye. Dev Biol 344:948-56
Cordero, Julia B; Cagan, Ross L (2010) Canonical wingless signaling regulates cone cell specification in the Drosophila retina. Dev Dyn 239:875-84
Cagan, Ross (2009) Principles of Drosophila eye differentiation. Curr Top Dev Biol 89:115-35
Larson, David E; Liberman, Zoe; Cagan, Ross L (2008) Cellular behavior in the developing Drosophila pupal retina. Mech Dev 125:223-32
Seppa, Midori J; Johnson, Ruth I; Bao, Sujin et al. (2008) Polychaetoid controls patterning by modulating adhesion in the Drosophila pupal retina. Dev Biol 318:1-16
Cordero, Julia B; Larson, David E; Craig, Caroline R et al. (2007) Dynamic decapentaplegic signaling regulates patterning and adhesion in the Drosophila pupal retina. Development 134:1861-71
Vidal, Marcos; Cagan, Ross L (2006) Drosophila models for cancer research. Curr Opin Genet Dev 16:10-6

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