Research
Development and regeneration in the vertebrate retina
My research involves studying cellular differentiation and gene expression in the vertebrate retina, the photosensitive lining at the back of the eye. The light-capturing neurons of the retina are the photoreceptors. Rod photoreceptors mediate dim light vision, whereas cone photoreceptors mediate daytime and color vision.
Photoreceptor degeneration associated with ocular diseases such as retinitis pigmentosa (RP), macular degeneration, and retinal detachment is a significant cause of visual impairment and blindness, for which there is currently no cure. One promising avenue of research is to study the retinas of vertebrate animals that innately possess the capacity to regenerate retinal neurons following injury. For this reason, the zebrafish retina represents a valuable model system in which to study the mechanisms of neural progenitor proliferation, differentiation, and photoreceptor regeneration.The zebrafish is a small, freshwater teleost that is easily reared in the laboratory. Zebrafish offer several advantages for genetic and developmental studies, including robust reproduction, optical transparency of the embryo, and rapid development. Relevant to my research, zebrafish (like humans) are diurnal animals, and the zebrafish retina contains a large number of cones in addition to rods, which is advantageous for studying daytime and color vision. Some of the methods I use to study the zebrafish visual system include standard molecular, biochemical and immunohistochemical techniques, as well as a variety of more sophisticated genetic and molecular methods such as transgenesis, forward and reverse genetic approaches, and the creation of genetic mosaics.
The ability of the teleost retina to regenerate following injury has been known for many years. Regeneration of the damaged retina involves three basic phases. First, there must be an increase in proliferation of germinal cells. Second, the progenitor cells must receive the appropriate signals from the local environment directing them to migrate and differentiate into the missing cell type. And finally, the newly differentiated neurons must integrate into the existing retinal circuitry. As this is precisely the sequence of events that must take place for cell-based transplantation therapies to be successful in the human retina, it is important to learn how each of these steps is controlled in zebrafish. Accordingly, one of the projects in my laboratory involves identifying the genetic pathways that mediate photoreceptor development and regeneration in zebrafish. A second project will explore the establishment and role of chromatin organization during photoreceptor development and regeneration. Overall, my research spans several areas of interest, including developmental neurobiology, genetics, molecular, and cellular biology.
Selected Publications
1. Alvarez-Delfin K., Morris A.C., Snelson C., Gamse J.T., Mullins M.C., and Fadool J.M. (2009) Tbx2b regulates rod versus cone photoreceptor cell fate during retinal development in zebrafish. Proc. Natl. Acad. Sci. 106(6): 2023-2028.
2. Morris A.C., Scholz T.L., Brockerhoff S.E. and Fadool J.M. (2008) Genetic dissection reveals two separate pathways for rod and cone regeneration in the teleost retina. Dev. Neurobiol. 68(5): 605-19.
3. Morris A.C., Scholz T., and Fadool J.M. (2008) Rod progenitor cells in the mature zebrafish retina. Adv Exp Med Biol 613: 361-368.
4. Morris A.C., Schroeter E.H., Bilotta J., Wong R.O.L., and Fadool J.M. (2005) Cone survival despite rod degeneration in XOPS-mCFP transgenic zebrafish. IOVS 46(12):4762-71.
5. Morris A.C. and Fadool J.M. (2005) Studying rod photoreceptor development in zebrafish. Physiol. Behav. 86(3):306-13.
6. Morris A.C., Beresford G.W., Mooney M.R., and Boss J.M. (2002) Kinetics of a gamma interferon response: expression and assembly of CIITA promoter IV and inhibition by methylation. Mol Cell Biol. 13:4781-91.
7. Morris A.C., Spangler W.E., and Boss J.M. (2000) Methylation of Class II trans-Activator promoter IV: A novel mechanism of MHC class II gene control. J. Immunol. 164: 4143-4149.
8. Ping D., Boekhoudt G., Zhang F., Morris A., Philipsen S., Warren S.T., and Boss J.M. (2000) Sp1 binding is critical for promoter assembly and activation of the MCP-1 gene by Tumor Necrosis Factor. J. Biol. Chem. 275: 1708-1714.
9. Moreno C.S., Beresford G.W., Louis-Plence P., Morris A.C., and Boss J.M. (1999) CREB regulates MHC class II expression in a CIITA-dependent manner. Immunity 10:143-1
10. Morris A.C., Riley J.L., Fleming W.H., and Boss J.M. (1998) MHC class II gene silencing in trophoblast cells is caused by inhibition of CIITA expression. Am. J. Reprod. Immunol. 40: 385-394.