More Than Meets the Eye: Molecular Diversity of the Intrinsically Photosensitive Ganglion Cells Regulating Circadian Photoentrainment

Berg, Daniel

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Year:: 2017
Contributor:: Berg, Daniel (creator); Berson, David (Advisor); Wessel, Gary (Reader); Barnea, Gilad (Reader); Morrow, Eric (Reader); Sanes, Joshua (Reader); Brown University. Department of Molecular Biology, Cell Biology and Biochemistry (sponsor)
Genre:: theses
Subject:: iprgcs; opn4; melanopsin; Retinal ganglion cells; rasgrp1; tbx20; rbp4; transgenic reporter; Circadian rhythms; Visual pathways; cell types; terminal differentiation; photoentrainment; molecular diversity; non-image forming; phototransduction; intrinsically photosensitive
Extent:: xviii, 275 p.
DOI: https://doi.org/10.26300/zh8v-qx46

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Abstract:: Chapters 1-3: Intrinsically photosensitive retinal ganglion cells (ipRGCs) are rare mammalian photoreceptors essential for non-image-forming vision functions, such as circadian photoentrainment and the pupillary light reflex. ipRGCs comprise multiple subtypes distinguishable by morphology, physiology, projections, and levels of expressed Opn4/Melanopsin, the ipRGC photopigment. Despite their neuronal specializations, the molecular identity and subtype-specific differences of ipRGCs remain elusive. Here, we present a comprehensive gene expression profiles of postnatal and adult mouse ipRGCs, suggesting dozens of genes not previously known to be highly enriched in ipRGCs. We reveal that Rasgrp1, a Ras GEF (guanine nucleotide exchange factor), and the T-box transcription factor Tbx20 are selectively expressed in a subpopulation of ipRGCs that are not restricted to a single, established type. Finally, we demonstrate that the ipRGCs regulating circadian photoentrainment are unexpectedly diverse at the molecular level. Our synthesis of previously unknown ipRGC markers provides a fuller appreciation of the complex molecular landscape across mammalian ipRGC types. Chapter 4: Genetically modified Cre strains permit cell-type-specific labeling and functional manipulations. We illustrate the utility of Rbp4-Cre mice for studying selected retinal cell types that encode the intensity of light and the direction of motion. Intensity encoding is thought to be uniquely mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs). ipRGCs transmit intensity signals not only to the brain, but also intraretinally, partly through gap junctions to polyaxonal amacrine cells. We show that these amacrine cells are tagged in Rbp4-Cre mice, confirm their persistent light responses under chemical synaptic blockade, and show that they co-stratify with, and are tracer-coupled to M2 ipRGCs. The line also labels a variant of direction-selective RGCs, and a RGC that lacks intrinsic photosensitivity but encodes intensity.
Notes:: Thesis (Ph. D.)--Brown University, 2017

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Rights: In Copyright
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Berg, Daniel, "More Than Meets the Eye: Molecular Diversity of the Intrinsically Photosensitive Ganglion Cells Regulating Circadian Photoentrainment" (2017). Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations. Brown Digital Repository. Brown University Library. https://doi.org/10.26300/zh8v-qx46

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Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations

Theses and Dissertations for the Molecular Biology, Cell Biology, and Biochemistry department.
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