This research proposal will define the ways in which neuroblasts of distinct laminar and functional fate disperse within the retina. Transgenic mice carrying the bacterial lacZ gene inserted on the X chromosome will be used, and the natural, random phenomenon of X inactivation in hemizygous females will restrict expression of the transgene to half of all retinal neurons. Since X inactivation occurs before any retinal neuroblasts have been born, and because progeny inherit the X-active status of their progenitors, this approach permits the marking of large numbers of retinal clones. Chimeric mice, formed by combining lacZ-expressing embryonic cells with wild-type embryos, will also be used to label small numbers of retinal clones in order to confirm the results from the X-inactivation transgenic mosaic mice. Retinae from both transgenic and chimeric adult mice show a conspicuous columnar arrangement of such clones of cells, but also reveal that distinct types of retinal cell do not respect this columnar segregation. The distributions of the clonally related cells suggest that the dispersion pattern of a neuroblast from the germinal zone of the developing retina can include a tangential as well as a radial component, but that the expression of the tangential component is confined to distinct subsets of retinal neuroblast. The present investigation will examine two hypotheses for this tangential dispersion. First, is tangential dispersion due to a passive displacement of these cells as the remainder of the retinal cells proliferate? And second, is the tangential dispersion due to an active displacement of the postmitotic neuroblasts, playing a role in the establishment of the orderly spacing between neurons of particular classes? Adult and developing retinae will be examined, in which cohorts of retinal cells sharing common birthdates will have been labelled during embryogenesis. Distinct types of retinal cells will b identified using immunocytochemistry to correlate phenotype and intercellular spacing with extent of tangential dispersion. These studies will clarify the mechanisms underlying the creation of the mature retinal architecture.
| Reese, Benjamin E; Keeley, Patrick W (2016) Genomic control of neuronal demographics in the retina. Prog Retin Eye Res 55:246-259 |
| Keeley, Patrick W; Sliff, Buranee J; Lee, Sammy C S et al. (2012) Neuronal clustering and fasciculation phenotype in Dscam- and Bax-deficient mouse retinas. J Comp Neurol 520:1349-64 |
| Reese, Benjamin E; Keeley, Patrick W; Lee, Sammy C S et al. (2011) Developmental plasticity of dendritic morphology and the establishment of coverage and connectivity in the outer retina. Dev Neurobiol 71:1273-85 |
| Reese, Benjamin E (2011) Development of the retina and optic pathway. Vision Res 51:613-32 |
| Petrs-Silva, Hilda; Dinculescu, Astra; Li, Qiuhong et al. (2011) Novel properties of tyrosine-mutant AAV2 vectors in the mouse retina. Mol Ther 19:293-301 |
| Whitney, Irene E; Raven, Mary A; Ciobanu, Daniel C et al. (2011) Genetic modulation of horizontal cell number in the mouse retina. Proc Natl Acad Sci U S A 108:9697-702 |
| Whitney, Irene E; Raven, Mary A; Lu, Lu et al. (2011) A QTL on chromosome 10 modulates cone photoreceptor number in the mouse retina. Invest Ophthalmol Vis Sci 52:3228-36 |
| Keeley, Patrick W; Reese, Benjamin E (2010) Morphology of dopaminergic amacrine cells in the mouse retina: independence from homotypic interactions. J Comp Neurol 518:1220-31 |
| Keeley, Patrick W; Reese, Benjamin E (2010) Role of afferents in the differentiation of bipolar cells in the mouse retina. J Neurosci 30:1677-85 |
| Petrs-Silva, Hilda; Dinculescu, Astra; Li, Qiuhong et al. (2009) High-efficiency transduction of the mouse retina by tyrosine-mutant AAV serotype vectors. Mol Ther 17:463-71 |
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