Research Interest
Development & Degenerative Diseases of the Visual System, Stem Cell Biology, Zebrafish Genetics
Current Projects
Our research goal is to identify fundamental mechanisms governing the development of the vertebrate central nervous system through systematic genetic and cellular analyses. We concentrate our efforts on the neural retina, the photosensitive lining of the back of the eye. Like many regions of the brain, the anatomical organization, biochemical processes and gene expression patterns in the retina are conserved in virtually all vertebrate species. Our hope is that an understanding of the pathways that regulate gene expression and ultimately cellular differentiation in the neural retina will aid in the identification and management of genetic disorders affecting the visual system such as retinitis pigmentosa, macular degeneration and glaucoma.
As a genetic model of vertebrate development, we utilize the zebrafish (Danio rerio), a small fresh water fish that is easily reared in the lab. Following in the footsteps of the genetic studies of Drosophila ommatidial arrangement, we are the first laboratory to successfully taking advantage of the well patterned mosaic of photoreceptors in zebrafish to uncover novel genes or novel gene functions regulating photoreceptor cell development in a vertebrate (Alvarez-Delfin, et al., 2009 PNAS). Students and fellows in the lab have also successfully discovered genetic mutations affecting photoreceptor cell survival, the development of the eye and the crystalline lens. In our studies we routinely use methods such as immunofluorescences, confocal microscopy, in situ hybridization, PCR and molecular genetics.
A second project in the laboratory explores molecular mechanisms regulating regeneration in the zebrafish retina (Morris, et al., Dev Neurobiology 2008). Unlike mammals, fish possess the ability to regenerate many tissues in response to injury or genetic lesions including the retina. Our laboratory developed the first genetic models showing specific photoreceptor cell loss to understand the cellular mechanisms regulating stem cell proliferation and neurogenesis. Using these genetic lines, we have characterized different regenerative responses to rod versus cone cell death.
Current Projects
We are currently seeking students to pursue two different projects in the laboratory. First, we are continuing the genetic screen for mutations affecting eye development and photoreceptor cell patterning. In this project, we hope to add more complex behavioral studies to answers questions related to the visual system function in the fish demonstrating changes in photoreceptor cell number and patterning. Secondly, we are continuing the investigations of photoreceptor cell regeneration. Current research is aimed at understanding signaling mechnisms that regulate the generation of new neurons by the two populations of stem cells and how the new neurons integrate into the existing retinal circuitry.
Publications
- Alvarez-Delfin K, Morris AC, Snelson CD, Gamse JT, Gupta T, Marlow FL, Mullins MC, Burgess HA, Granato M, Fadool JM. Tbx2b is required for ultraviolet photoreceptor cell specification during zebrafish retinal development. Proc Natl Acad Sci U S A. 106:2023-2028. (2009) Abstract
- Morris AC, Scholz TL, Brockerhoff SE, Fadool JM. Genetic dissection reveals two separate pathways for rod and cone regeneration in the teleost retina. Dev Neurobiol. 68:605-19. (2008) Abstract
- Fadool JM, Dowling JE. Zebrafish: A Model System for the Study of Eye Genetics. Prog Retin Eye Res. 1, 89-110. (2008) Abstract
- Stearns G, Evangelista M, Fadool JM, Brockerhoff SE. A mutation in the cone-specific pde6 gene causes rapid cone photoreceptor degeneration in zebrafish. J Neurosci. 27:13866-74. (2007) Abstract
- Fuller RC, Carleton KL, Fadool JM, Spady TC, Travis J. Genetic and environmental variation in the visual properties of bluefin killifish, Lucania goodei. J Evol Biol. 18:516-23. (2005) Abstract
- Vihtelic TS, Fadool JM, Thornton K, Hyde DR, Wistow G. Expressed sequence tag analysis of zebrafish eye tissues for NEIBank. Mol Vision. 11:1083-1100. (2005) Abstract
- Morris AC, Schroeter EH, Bilotta J, Wong RO, Fadool JM. Cone survival despite rod degeneration in transgenic zebrafish. Invest Ophthalmol Visual Sci. 46:4762-4771. (2005) Abstract
- DeCarvalho AC, Cappendijk S, Fadool JM. Expression of the Pou domain transcription factor, Brn3b in the lateral line and retina of zebrafish. Dev Dynamics. 229:869-876. (2004) Abstract
- Fadool JM. Development of a rod photoreceptor mosaic revealed in transgenic zebrafish. Dev Biol. 258:277-290. (2003) Abstract
- McCune AR, Fuller RC, Aquilina AA, Dawley RM, Fadool JM, Houle D, Travis J, Kondrashov AS. A low genomic number of recessive lethals in natural populations of bluefin killifish and zebrafish. Science. 296:2398-401. (2002) Abstract
- Fadool JM, Hartl DL, Dowling JE. Transposition of the mariner element from Drosophila mauritiana in zebrafish (Danio rerio). Proc Natl Acad Sci USA. 95:5182-5186. (1998) Abstract
- Fadool JM, Brockerhoff SE, Hyatt GA, Dowling JE. Mutations affecting eye morphology in the developing zebrafish (Danio rerio). Dev Genetics. 20:288-295. (1997) Abstract