Skip to main content
Article thumbnail
Location of Repository

Identification of molecular markers of bipolar cells in the murine retina

By Douglas S Kim, Sarah E Ross, Jeffrey M Trimarchi, John Aach, Michael E Greenberg and Constance L Cepko

Abstract

Retinal bipolar neurons serve as relay interneurons that connect rod and cone photoreceptor cells to amacrine and ganglion cells. They exhibit diverse morphologies essential for correct routing of photoreceptor cell signals to specific postsynaptic amacrine and ganglion cells. The development and physiology of these interneurons have not been completely defined molecularly. Despite previous identification of genes expressed in several bipolar cell subtypes, molecules that mark each bipolar cell type still await discovery. In this report, novel genetic markers of murine bipolar cells were found. Candidates were initially generated by using microarray analysis of single bipolar cells and mining of retinal serial analysis of gene expression (SAGE) data. These candidates were subsequently tested for expression in bipolar cells by RNA in situ hybridization. Ten new molecular markers were identified, five of which are highly enriched in their expression in bipolar cells within the adult retina. Double-labeling experiments using probes for previously characterized subsets of bipolar cells were performed to identify the subtypes of bipolar cells that express the novel markers. Additionally, the expression of bipolar cell genes was analyzed in Bhlhb4 knockout retinas, in which rod bipolar cells degenerate postnatally, to delineate further the identity of bipolar cells in which novel markers are found. From the analysis of Bhlhb4 mutant retinas, cone bipolar cell gene expression appears to be relatively unaffected by the degeneration of rod bipolar cells. Identification of molecular markers for the various subtypes of bipolar cells will lead to greater insights into the development and function of these diverse interneurons

Topics: Article
Publisher: Wiley Subscription Services, Inc., A Wiley Company
OAI identifier: oai:pubmedcentral.nih.gov:2665264
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles

    Citations

    1. (2003). A comparison of immunocytochemical markers to identify bipolar cell types in human and monkey retina.
    2. (1995). A novel family of genes encoding putative pheromone receptors in mammals.
    3. (2006). AII amacrine cells in the distal inner nuclear layer of the mouse retina.
    4. (1998). Alpha subunit of Go localizes in the dendritic tips of ON bipolar cells.
    5. (2003). Basic helix-loop-helix factors in cortical development.
    6. (2003). BETA2/NeuroD1 null mice: a new model for transcription factordependent photoreceptor degeneration.
    7. (2004). Bipolar cells of the mouse retina: a gene gun, morphological study.
    8. (1984). Cell death during differentiation of the retina in the mouse.
    9. (1985). Cell differentiation in the retina of the mouse. Anat Rec 212:199–205.
    10. (1991). Cerebellar Purkinje cell markers are expressed in retinal bipolar neurons.
    11. (1985). cGMP phosphodiesterase in rod and cone outer segments of the retina.
    12. (1992). Cloning of the cDNA for a novel photoreceptor membrane protein (rom-1) identifies a disk rim protein family implicated in human retinopathies.
    13. (2004). Comparative gene expression analysis of murine retina and brain. Mol Vis 10:637–649.
    14. (1991). Complete cDNA sequences of mouse rod photoreceptor cGMP phosphodiesterase alphaand beta-subunits, and identification of beta-, a putative beta-subunit isozyme produced by alternative splicing of the beta-subunit gene.
    15. (2005). Comprehensive in silico functional specification of mouse retina transcripts.
    16. (1993). Construction of cDNA libraries from single cells. Methods Enzymol 225:611–623.
    17. (2004). Control of late off-center cone bipolar cell differentiation and visual signaling by the homeobox gene Vsx1. Proc Natl Acad SciUSA101:1754–1759.
    18. (1997). Conversion of ectoderm into a neural fate by ATH-3, a vertebrate basic helix-loop-helix gene homologous to Drosophila proneural gene atonal.
    19. (1994). Developmental expression of a novel murine homeobox gene (Chx10): evidence for roles in determination of the neuroretina and inner nuclear layer.
    20. (1978). Differential effect of the rd mutation on rods and cones in the mouse retina. Invest Ophthalmol Vis Sci 17:489–498.
    21. (2004). Electroporation and RNA interference in the rodent retina in vivo and in vitro.
    22. (2007). Expression of the LIMhomeodomain protein Isl1 in the developing and mature mouse retina.
    23. (2002). F3/contactin, a neuronal cell adhesion molecule implicated in axogenesis and myelination.
    24. (2000). Five members of a novel Ca(2)-binding protein (CABP) subfamily with similarity to calmodulin.
    25. (1998). GABAA and GABAC receptors on mammalian rod bipolar cells.
    26. (1988). Gamma-subunit of mouse retinal cyclic-GMP phosphodiesterase: cDNA and corresponding amino acid sequence.
    27. (1998). Gene array and expression of mouse retina guanylate cyclase activating proteins 1 and 2. Invest Ophthalmol Vis Sci 39:867–875.
    28. (2003). gene expression defines the retinal ganglion and inner nuclear layers of the developing and adult mouse retina.
    29. (2004). Genetic analysis of the homeodomain transcription factor Chx10 in the retina using a novel multifunctional BAC transgenic mouse reporter.
    30. (2007). Genome-wide atlas of gene expression in the adult mouse brain.
    31. (2004). Genomic analysis of mouse retinal development. PLoS Biol 2:E247.
    32. (2004). Global gene expression analysis of the developing postnatal mouse retina. Invest Ophthalmol Vis Sci 45:1009–1019.
    33. (2005). Identification of regulatory targets of tissue-specific transcription factors: application to retina-specific gene regulation.
    34. (1986). Identification of specific transducin alpha subunits in retinal rod and cone photoreceptors.
    35. (2003). Immunocytochemical description of five bipolar cell types of the mouse retina.
    36. (1995). Immunocytochemical identification of cone bipolar cells in the rat retina.
    37. (1983). Immunocytochemical localization of two retinoid-binding proteins in vertebrate retina.
    38. (2001). Isolation and characterization of Vsx1, a novel mouse CVC paired-like homeobox gene expressed during embryogenesis and in the retina.
    39. (1990). Localization of two calcium binding proteins, calbindin (28 kD) and parvalbumin (12 kD), in the vertebrate retina.
    40. (2007). Molecular and cellular alterations induced by sustained expression of ciliary neurotrophic factor in a mouse model of retinitis pigmentosa.
    41. (1993). Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4-phosphonobutyrate.
    42. (1994). Molecular characterization of human and mouse photoreceptor guanylate cyclase-activating protein (GCAP) and chromosomal localization of the human gene.
    43. (1998). Molecular forms of human rhodopsin kinase (GRK1).
    44. (1983). Monoclonal antibodies to rhodopsin: characterization, cross-reactivity, and application as structural probes.
    45. (1977). Muller cell localisation of glutamine synthetase in rat retina.
    46. (1996). Ocular retardation mouse caused by Chx10 homeobox null allele: impaired retinal progenitor proliferation and bipolar cell differentiation.
    47. (1997). ON cone bipolar cells in rat express the metabotropic receptor mGluR6. Vis Neurosci 14:789–794.
    48. (1995). Overlapping and differential expression of BIG-2, BIG-1, TAG-1, and F3: four members of an axon-associated cell adhesion molecule subgroup of the immunoglobulin superfamily.
    49. (1989). Primary structure and functional expression from complementary DNA of the rod photoreceptor cyclic GMP-gated channel.
    50. (2007). Reactive changes of retinal astrocytes and Muller glial cells in kainate-induced neuroexcitotoxicity.
    51. (2004). Regulation of retinal cone bipolar cell differentiation and photopic vision by the CVC homeobox gene Vsx1. Curr Biol 14:530–536.
    52. (2002). Representation is faithfully preserved in global cDNA amplified exponentially from sub-picogram quantities of mRNA.
    53. (2004). Retinal cell fate determination and bHLH factors.
    54. (1992). Retinal rods and cones have distinct G protein beta and gamma subunits.
    55. (1990). Rod bipolar cells in the mammalian retina show protein kinase C-like immunoreactivity.
    56. (2003). Singlecell transcriptional analysis of neuronal progenitors.
    57. (1999). Sonic hedgehog promotes The
    58. (1992). Structure of the axonal surface recognition molecule neurofascin and its relationship to a neural subgroup of the immunoglobulin superfamily.
    59. (1998). Synaptic clustering of GABA(C) receptor rho-subunits in the rat retina.
    60. (1992). Targeted mutation of the DNA methyltransferase gene results in embryonic lethality.
    61. (2007). The cis-regulatory logic of the mammalian photoreceptor transcriptional network. PLoS
    62. (2002). The Leber congenital amaurosis gene product AIPL1 is localized exclusively in rod photoreceptors of the adult human retina. Hum Mol Genet 11:823–831.
    63. (1998). The major cell populations of the mouse retina.
    64. (1997). The mGluR6 5 upstream transgene sequence directs a cell-specific and developmentally regulated expression in retinal rod and ON-type cone bipolar cells.
    65. (2000). The subcellular localization of Otx2 is cell-type specific and developmentally regulated in the mouse retina.
    66. (2004). The transcription factor Bhlhb4 is required for rod bipolar cell maturation.
    67. (2007). Two mouse retinal degenerations caused by missense mutations in the beta-subunit of rod cGMP phosphodiesterase gene.
    68. (2005). Two ribeye genes in teleosts: the role of Ribeye in ribbon formation and bipolar cell development.
    69. (2004). Types of bipolar cells in the mouse retina.
    70. (1974). Ultrastructural localization of rhodopsin in the vertebrate retina.
    71. (2001). Vsx1, a rapidly evolving paired-like homeobox gene expressed in cone bipolar cells.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.