Tiffany Cook, PhD
Cell Type Specification During Eye Development
Our lab is interested in understanding the molecular basis of eye development, and how these processes are disrupted in disease states. Using the fruit fly Drosophila melanogaster as a model, we combine cellular, molecular, biochemical, and genetic approaches to dissect the events underlying the development of the retina. These studies have led to the finding that many of the same factors involved in retinogenesis in the fly are also necessary for vertebrate eye development. For instance, Crx/Otd is a transcription factor necessary for photoreceptor differentiation in flies, mice, and humans, and mutations in this gene are responsible for retinal dystrophic diseases such as retinitis pigmentosa (RP), Leber amaurosis, and cone-rod dystrophy. Thus, our studies will not only help to understand basic developmental questions related to how different cell types arise and the conservation of retinal cell type differentiation across species, but should also aid us in developing tools for fighting otherwise blinding human diseases.
Our lab has also recently led to the identification of a new genetic pathway that is necessary for lens formation in species ranging from flies to humans. This pathway involves the recently identified tumor suppressor, Prospero, and provides some of the first evidence that lens development is conserved between vertebrate camera-like eyes and invertebrate compound eyes. The work also has important implications for patients suffering from cataract disease.
Areas of research include:
- Differentiation of color photoreceptor subtypes in the Drosophila retina
- Cell-specific regulation of opsin gene expression
- Mechanisms of cell-specific transcriptional activation and repression
Publications
McDonald EC, Workman M, Reischl J, Meier K , Wimmer E, Gebelein B, Cook TA. Distinct spatial-specific regulatory domains are important for Otd/Otx-mediated regulation of nervous system development (in preparation)
Li-Kroeger D, Witt LM, Grimes HL, Cook TA, Gebelein B. Hox and Senseless antagonism functions as a molecular switch to regulate EGF secretion in the Drosophila PNS. Dev Cell 15:298-308, 2008
Mazzoni EO, Celik A, Wernet MW, Vasiliauskas D, Cook TA, Johnston RJ, Pichaud F, Desplan C. Iroquois-Complex genes induce co-expression of visual pigments in Drosophila. PLoS Biology 6(4):e97, 2008
Ranade SS, Yang-Zhou D, Kong SW, McDonald EC, Cook TA, and Pignoni F. The regulation of photoperception-related genes by Otd supports the conservation of CRX/OTX/OTD gene family functions in flies and vertebrates. Dev Biol 315(2):521-34, 2008.
Xie B, Charlton-Perkins M, McDonald EC, Gebelein B, Cook TA. Senseless functions as a molecular switch for color photoreceptor differentiation in Drosophila. Development 134:4243-4253, 2007.
Jackowska M, Bao R, Liu Z, McDonald EC, Cook TA, and Friedrich M. Replacement and loss of blue sensitive photoreceptors through expansion of green and UV-green double sensitive photoreceptors in the red flour beetle Tribolium castaneu. BMC Frontiers in Zoology 4:24, 2007
Neve C, Fernandez-Zapico ME, Ashkenazi-Katalan V, Dina C, Hamid YH, Joly E, Vaillant E, Benmezrona Y, Durand E, Bakaher N, Delannoy V, Vaxillnire M, Cook T, Dallina-Thie GM, Jansen H, Charles MA, Clement K, Galan P, Hercberg S, Helgecque N, Charpentier G, Prentki M, Hansen T, Perdersen O, Urrutia R, Melloul D. Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic b-cell function. PNAS 2005;102:4807-12.
Cao S, Fernandez-Zapico ME, Jin D, Puri V, Cook TA, Lerman LO, Zhu XY, Urrutia R, Shah V. KLF11-mediated repression antagonizes Sp1/sterol-responsive element-binding protein-induced transcriptional activation of caveolin-1 in response to cholesterol signaling. J Biol Chem 2005;280:1901-10.
Tahayato A, Sonneville R, Pichaud F, Papatsenko D, Beaufils P, Wernet M, Cook T, Desplan C. Otd/Crx, a dual regulator for the mosaic expression of Drosophila rhodopsins. Dev Cell 2003;5:391-402.
Cook T, Pichaud F, Sonneville R, Papatsenko D, Desplan C. Distinction between color photoreceptor cell fates is controlled by Prospero in Drosophila. Dev Cell 2003;4:853-64. (selected as F1000 Biology must read article; cover image)
Cook T. Cell diversity in the retina: More than meets the eye. Bioessays 2003;25:921-25.
Kaczynski J, Cook T, and Urrutia R. Sp1- and Kruppel-like transcription factors. Genome Biology 2003;4:206.
Cook T, Desplan C. Photoreceptor subtype specification: from flies to humans. Sem Cell Dev Biol 2001;12:509-18.
Contact Information
Tiffany Cook, PhD
TCHRF 3045, MLC 7007
3333 Burnet Avenue, CCHMC
Cincinnati, OH 45229
Email: tiffany.cook@cchmc.org
Phone: 513-636-6991 (office); 513-636-1659 (lab)
