This proposal describes an anatomical investigation of the addition of new neurons and the resultant reorganizations of synaptic connectivity which occur during postembryonic growth of teleost fish. The focus is on two principle topics: changes in retinal cytoarchitecture resulting from ontogenetic differences between rods and cones and changes in the sites of termination of individual retinal fibers in the growing optic tectum. There are three specific aims. 1.) To characterize the population of photoreceptors in goldfish of different sizes, especially with regard to the accumulation of rods in the growing retina, and to determine whether structural changes occur in individual photoreceptors with age. 2.) To identify the progenitor cells which generate new rods. These dividing cells are located in the outer nuclear layer, amongst mature rod nuclei; they have been identified only with thymidine radioautography but have never been described in ultrastructural studies. The role of rod progenitors will be assessed in the normal retina (do they only add to the rod population or are some of their progeny replacements for rods lost through cell death?) and in the regenerating retina (are they able to generate retinal neurons other than rods under those circumstances?). The ontogenetic history of rod progenitors will be investigated in larval retinas to determine where these unique cells come from. 3.) To chart the tectotopic positions of individual retinal terminals over time using long-lasting neuroanatomical markers. Because retina and tectum grow along non-equivalent dimensions, it has been suggested that systematic shifts occur in the retinotectal map, and it is this hypothesis which is to be tested. The anatomical studies of photoreceptor development in teleost retina will provide information about how rods and cones differ that may be significant for understanding disease processes which preferentially affect specific photoreceptors. The analysis of retinotectal projections may provide evidence for naturally-occuring changes in synaptic connectivity that would contribute to our understanding of development and regeneration of neuronal connections.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004318-03
Application #
3258714
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1983-04-01
Project End
1986-04-30
Budget Start
1985-04-01
Budget End
1986-04-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Sifuentes, Christopher J; Kim, Jung-Woong; Swaroop, Anand et al. (2016) Rapid, Dynamic Activation of Müller Glial Stem Cell Responses in Zebrafish. Invest Ophthalmol Vis Sci 57:5148-5160
Lenkowski, Jenny R; Raymond, Pamela A (2014) Müller glia: Stem cells for generation and regeneration of retinal neurons in teleost fish. Prog Retin Eye Res 40:94-123
Nagashima, Mikiko; Barthel, Linda K; Raymond, Pamela A (2013) A self-renewing division of zebrafish Muller glial cells generates neuronal progenitors that require N-cadherin to regenerate retinal neurons. Development 140:4510-21
Lenkowski, Jenny R; Qin, Zhao; Sifuentes, Christopher J et al. (2013) Retinal regeneration in adult zebrafish requires regulation of TGF? signaling. Glia 61:1687-97
Qin, Zhao; Raymond, Pamela A (2012) Microarray-based gene profiling analysis of Müller glia-derived retinal stem cells in light-damaged retinas from adult zebrafish. Methods Mol Biol 884:255-61
Meyers, Jason R; Hu, Lily; Moses, Ariel et al. (2012) ?-catenin/Wnt signaling controls progenitor fate in the developing and regenerating zebrafish retina. Neural Dev 7:30
Qin, Zhao; Kidd 3rd, Ambrose R; Thomas, Jennifer L et al. (2011) FGF signaling regulates rod photoreceptor cell maintenance and regeneration in zebrafish. Exp Eye Res 93:726-34
Qin, Zhao; Barthel, Linda K; Raymond, Pamela A (2009) Genetic evidence for shared mechanisms of epimorphic regeneration in zebrafish. Proc Natl Acad Sci U S A 106:9310-5
Adler, Ruben; Raymond, Pamela A (2008) Have we achieved a unified model of photoreceptor cell fate specification in vertebrates? Brain Res 1192:134-50
Bernardos, Rebecca L; Barthel, Linda K; Meyers, Jason R et al. (2007) Late-stage neuronal progenitors in the retina are radial Muller glia that function as retinal stem cells. J Neurosci 27:7028-40

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