We study the gene networks that transform the embryonic cells into a complex, differentiated organ. We focused on exploring this question by studying the process of eye development as a model for organogenesis. We apply cutting-edge technologies including mouse genetic tools (Cre/loxP), molecular biology, and microarray analysis to identify and functionally characterize genes that regulate the development of the eye in mammals. Understanding the normal developmental regulation of the different eye structures is essential for understanding visual disorders and designing treatments for ocular phenotypes including retinal degeneration, glaucoma and cataracts, all of which are leading causes of blindness. Current topics of research in the laboratory include: Study of gene networks controlling cell fate decisions in retinal neurogenesis. (1-5) Study of the molecular mechanisms regulating lens development (6-11) Investigating the transcription factors regulating the development of the pigmented cell types of the eye; retinal pigmented epithelium, iris and ciliary body. (12-14) Investigating the roles of miRNA in eye development. (15) 1. Marquardt T, Ashery-Padan R, Andrejewski N, Scardigli R, Guillemot F, Gruss P: Pax6 is required for the multipotent state of retinal progenitor cells. Cell 2001, 105:43-55. 2. Yaron O, Farhy C, Marquardt T, Applebury M, Ashery-Padan R: Notch1 functions to suppress conephotoreceptor fate specification in the developing mouse retina. Development 2006, 133:1367-1378. 3. Bumsted-O'Brien KM, Hendrickson A, Haverkamp S, Ashery-Padan R, Schulte D: Expression of the homeodomain transcription factor Meis2 in the embryonic and postnatal retina. J Comp Neurol 2007, 505:58-72. 4. Oron-Karni V, Farhy C, Elgart M, Marquardt T, Remizova L, Yaron O, Xie Q, Cvekl A, Ashery-Padan R: Dual requirement for Pax6 in retinal progenitor cells. Development 2008, 135:4037-4047. 5. Xu S, Sunderland ME, Coles BL, Kam A, Holowacz T, Ashery-Padan R, Marquardt T, McInnes RR, van der Kooy D: The proliferation and expansion of retinal stem cells require functional Pax6. Dev Biol 2007, 304:713-721. 6. Ashery-Padan R, Marquardt T, Zhou X, Gruss P: Pax6 activity in the lens primordium is required for lens formation and for correct placement of a single retina in the eye. Genes Dev 2000, 14:2701-2711. 7. Pontoriero GF, Deschamps P, Ashery-Padan R, Wong R, Yang Y, Zavadil J, Cvekl A, Sullivan S, Williams T, West-Mays JA: Cell autonomous roles for AP-2alpha in lens vesicle separation and maintenance of the lens epithelial cell phenotype. Dev Dyn 2008, 237:602-617. 8. Dwivedi DJ, Pontoriero GF, Ashery-Padan R, Sullivan S, Williams T, West-Mays JA: Targeted Deletion of AP-2{alpha} Leads to Disruption in Corneal Epithelial Cell Integrity and Defects in the Corneal Stroma. Invest Ophthalmol Vis Sci 2005, 46:3623-3630. 9. Smith AN, Miller LA, Radice G, Ashery-Padan R, Lang RA: Stage-dependent modes of Pax6-Sox2 epistasis regulate lens development and eye morphogenesis. Development 2009, 136:29772985. 10. Shaham O, Smith AN, Robinson ML, Taketo MM, Lang RA, Ashery-Padan R: Pax6 is essential for lens fiber cell differentiation. Development 2009, 136:2567-2578. 11. He S, Pirity MK, Wang WL, Wolf L, Chauhan BK, Cveklova K, Tamm ER, Ashery-Padan R, Metzger D, Nakai A, et al.: Chromatin remodeling enzyme Brg1 is required for mouse lens fiber cell terminal differentiation and its denucleation. Epigenetics Chromatin 2010, 3:21. 12. Davis N, Yoffe C, Raviv S, Antes R, Berger J, Holzmann S, Stoykova A, Overbeek PA, Tamm ER, AsheryPadan R: Pax6 dosage requirements in iris and ciliary body differentiation. Dev Biol 2009, 333:132-142. 13. Davis-Silberman N, Ashery-Padan R: Iris development in vertebrates; genetic and molecular considerations. Brain Res 2008, 1192:17-28. 14. Davis-Silberman N, Kalich T, Oron-Karni V, Marquardt T, Kroeber M, Tamm ER, Ashery-Padan R: Genetic dissection of Pax6 dosage requirements in the developing mouse eye. Hum Mol Genet 2005, 14:2265-2276. 15. Davis N, Mor E, Ashery-Padan R: Roles for Dicer1 in the patterning and differentiation of the optic cup neuroepithelium. Development 2011, 138:127-138.