Vertebrate cone photoreceptors are responsible for color and daytime vision. They have been extensively studied and much is known about their structure and function. For example, anatomical studies have described the morphologies of cone cells, the types of synpases they form and how they can adapt their shape in response to environmental and circadian factors. Furthermore, electrophysiological studies have described the physiological properties of cone responses to brief flashes of light and to steady illumination. Nevertheless there are many unanswered questions about cone structure and function. For example, although the physiological description of cone adaptation to illumination is well documented, the biochemical mechanism underlying this response is unknown. In addition, the mechanisms by which ribbon synapses form and are regulated are unknown. Finally many factors that influence cone photoreceptor shape and viability have yet to be discovered. In this proposal the investigators use zebrafish to identify genes essential for normal cone structure and function. The proposal relies heavily on the previous success of the investigator to identify genes essential for vertebrate cone function using a similar screening strategy.
The specific aims of the proposal are:
Specific Aim# l: Identify recessive mutations that are essential for normal cone photoreceptor function using an OKR behavioral screen followed by ERG analysis.
Specific Aim#2 : Perform histological analyses of the retinas of mutants with defects in cone photoreceptor function.
Specific Aim #3 : Identify the mutated genes by positional cloning and candidate gene analysis. All resources generated from this proposal will be made available to the scientific community. A specific plan for distributing the resources generated from this proposal has been designed with investigators at the zebrafish resource center in Oregon. This plan is presented as part of the proposal.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY015165-04
Application #
7100120
Study Section
Special Emphasis Panel (ZRG1-CDF-5 (50))
Program Officer
Mariani, Andrew P
Project Start
2003-08-13
Project End
2008-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
4
Fiscal Year
2006
Total Cost
$296,075
Indirect Cost
Name
University of Washington
Department
Biochemistry
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
George, Ashley A; Hayden, Sara; Stanton, Gail R et al. (2016) Arf6 and the 5'phosphatase of synaptojanin 1 regulate autophagy in cone photoreceptors. Bioessays 38 Suppl 1:S119-35
George, Ashley A; Hayden, Sara; Stanton, Gail R et al. (2016) Arf6 and the 5'phosphatase of Synaptojanin 1 regulate autophagy in cone photoreceptors. Inside Cell 1:117-133
Lewis, Alaron A; Mahoney, Joseph T; Wilson, Neil et al. (2015) Identification of amacrine subtypes that express the atypical cadherin celsr3. Exp Eye Res 130:51-7
Decker, Amanda R; McNeill, Matthew S; Lambert, Aaron M et al. (2014) Abnormal differentiation of dopaminergic neurons in zebrafish trpm7 mutant larvae impairs development of the motor pattern. Dev Biol 386:428-39
George, Ashley A; Hayden, Sara; Holzhausen, Lars C et al. (2014) Synaptojanin 1 is required for endolysosomal trafficking of synaptic proteins in cone photoreceptor inner segments. PLoS One 9:e84394
Lewis, Alaron; Wilson, Neil; Stearns, George et al. (2011) Celsr3 is required for normal development of GABA circuits in the inner retina. PLoS Genet 7:e1002239
Brockerhoff, Susan E (2011) Phosphoinositides and photoreceptors. Mol Neurobiol 44:420-5
Ile, Kristina E; Kassen, Sean; Cao, Canhong et al. (2010) Zebrafish class 1 phosphatidylinositol transfer proteins: PITPbeta and double cone cell outer segment integrity in retina. Traffic 11:1151-67
Holzhausen, Lars C; Lewis, Alaron A; Cheong, Kimberly K et al. (2009) Differential role for synaptojanin 1 in rod and cone photoreceptors. J Comp Neurol 517:633-44
Trapani, Josef G; Obholzer, Nikolaus; Mo, Weike et al. (2009) Synaptojanin1 is required for temporal fidelity of synaptic transmission in hair cells. PLoS Genet 5:e1000480

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