Hostname: page-component-cd9895bd7-fscjk Total loading time: 0 Render date: 2024-12-19T13:48:08.720Z Has data issue: false hasContentIssue false
  • English
  • Français

In vivo development of retinal ON-bipolar cell axonal terminals visualized in nyx::MYFP transgenic zebrafish

Published online by Cambridge University Press:  04 October 2006

ERIC H. SCHROETER ,
RACHEL O.L. WONG  and
RONALD G. GREGG
ERIC H. SCHROETER
Affiliation:
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri
RACHEL O.L. WONG
Affiliation:
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri
RONALD G. GREGG
Affiliation:
Department of Biochemistry and Molecular Biology, and Center for Genetics and Molecular Medicine, University of Louisville, Louisville, Kentucky
Get access Rights & Permissions [Opens in a new window]

Abstract

Axonal differentiation of retinal bipolar cells has largely been studied by comparing the morphology of these interneurons in fixed tissue at different ages. To better understand how bipolar axonal terminals develop in vivo, we imaged fluorescently labeled cells in the zebrafish retina using time-lapse confocal and two photon microscopy. Using the upstream regulatory sequences from the nyx gene that encodes nyctalopin, we constructed a transgenic fish in which a subset of retinal bipolar cells express membrane targeted yellow fluorescent protein (MYFP). Axonal terminals of these YFP-labeled bipolar cells laminated primarily in the inner half of the inner plexiform layer, suggesting that they are likely to be ON-bipolar cells. Transient expression of MYFP in isolated bipolar cells indicates that two or more subsets of bipolar cells, with one or two terminal boutons, are labeled. Live imaging of YFP-expressing bipolar cells in the nyx::MYFP transgenic fish at different ages showed that initially, filopodial-like structures extend and retract from their primary axonal process throughout the inner plexiform layer (IPL). Over time, filopodial exploration becomes concentrated at discrete foci prior to the establishment of large terminal boutons, characteristic of the mature form. This sequence of axonal differentiation suggests that synaptic targeting by bipolar cell axons may involve an early process of trial and error, rather than a process of directed outgrowth and contact. Our observations represent the first in vivo visualization of axonal development of bipolar cells in a vertebrate retina.

Keywords

ZebrafishBipolar cellNyctalopinAxonal development
Type
Research Article
Information
Visual Neuroscience , Volume 23 , Issue 5 , September 2006 , pp. 833 - 843
Copyright
2006 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Bech-Hansen, N.T., Naylor, M.J., Maybaum, T.A., Sparkes, R.L., Koop, B., Birch, D.G., Bergen, A.A., Prinsen, C.F., Polomeno, R.C., Gal, A., Drack, A.V., Musarella, M.A., Jacobson, S.G., Young, R.S., & Weleber, R.G. (2000). Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness. Nature Genetics 26, 319–323.CrossRefGoogle Scholar
Behrens, U.D. & Wagner, H.J. (1996). Adaptation-dependent changes of bipolar cell terminals in fish retina: Effects on overall morphology and spinule formation in Ma and Mb cells. Vision Research 36, 3901–3911.CrossRefGoogle Scholar
Bramblett, D.E., Pennesi, M.E., Wu, S.M., & Tsai, M.J. (2004). The transcription factor Bhlhb4 is required for rod bipolar cell maturation. Neuron 43, 779–793.CrossRefGoogle Scholar
Branchek, T. (1984). The development of photoreceptors in the zebrafish, brachydanio rerio. II. Function. Journal of Comparative Neurology 224, 116–122.Google Scholar
Burmeister, M., Novak, J., Liang, M.Y., Basu, S., Ploder, L., Hawes, N.L., Vidgen, D., Hoover, F., Goldman, D., Kalnins, V.I., Roderick, T.H., Taylor, B.A., Hankin, M.H., & McInnes, R.R. (1996). Ocular retardation mouse caused by Chx10 homeobox null allele: Impaired retinal progenitor proliferation and bipolar cell differentiation. Nature Genetics 12, 376–384.CrossRefGoogle Scholar
Cheng, C.W., Chow, R.L., Lebel, M., Sakuma, R., Cheung, H.O., Thanabalasingham, V., Zhang, X., Bruneau, B.G., Birch, D.G., Hui, C.C., McInnes, R.R., & Cheng, S.H. (2005). The Iroquois homeobox gene, Irx5, is required for retinal cone bipolar cell development. Journal of Developmental Biology 287, 48–60.CrossRefGoogle Scholar
Chow, R.L., Volgyi, B., Szilard, R.K., Ng, D., McKerlie, C., Bloomfield, S.A., Birch, D.G., & McInnes, R.R. (2004). Control of late off-center cone bipolar cell differentiation and visual signaling by the homeobox gene Vsx1. Proceedings of the National Academy of Sciences 101, 1754–1759.CrossRefGoogle Scholar
Connaughton, V.P., Behar, T.N., Liu, W.L., & Massey, S.C. (1999). Immunocytochemical localization of excitatory and inhibitory neurotransmitters in the zebrafish retina. Visual Neuroscience 16, 483–490.Google Scholar
Connaughton, V.P., Graham, D., & Nelson, R. (2004). Identification and morphological classification of horizontal, bipolar, and amacrine cells within the zebrafish retina. Journal of Comparative Neurology 477, 371–385.CrossRefGoogle Scholar
Connaughton, V.P. & Nelson, R. (2000). Axonal stratification patterns and glutamate-gated conductance mechanisms in zebrafish retinal bipolar cells. Journal of Physiology 524, 135–146.CrossRefGoogle Scholar
Cooper, M.S., Szeto, D.P., Sommers-Herivel, G., Topczewski, J., Solnica-Krezel, L., Kang, H.C., Johnson, I., & Kimelman, D. (2005). Visualizing morphogenesis in transgenic zebrafish embryos using BODIPY TR methyl ester dye as a vital counterstain for GFP. Developmental Dynamics 232, 359–368.CrossRefGoogle Scholar
Crooks, J., Okada, M., & Hendrickson, A.E. (1995). Quantitative analysis of synaptogenesis in the inner plexiform layer of macaque monkey fovea. Journal of Comparative Neurology 360, 349–362.CrossRefGoogle Scholar
Dubin, M.W. (1970). The inner plexiform layer of the vertebrate retina: a quantitative and comparative electron microscopic analysis. Journal of Comparative Neurology 140, 479–505.CrossRefGoogle Scholar
Easter, S.S., Jr. & Nicola, G.N. (1996). The development of vision in the zebrafish (Danio rerio). International Journal of Developmental Biology 180, 646–663.Google Scholar
Godinho, L., Mumm, J.S., Williams, P.R., Schroeter, E.H., Koerber, A., Park, S.W., Leach, S.D., & Wong, R.O.L. (2005). Targeting of amacrine cell neurites to appropriate synaptic laminae in the developing zebrafish retina. Development 132, 5069–5079.Google Scholar
Gregg, R.G., Mukhopadhyay, S., Candille, S.I., Ball, S.L., Pardue, M.T., McCall, M.A., & Peachey, N.S. (2003). Identification of the gene and the mutation responsible for the mouse nob phenotype. Investigative Ophthalmology and Visual Science 44, 378–384.CrossRefGoogle Scholar
Gunhan-Agar, E., Choudary, P.V., Landerholm, T.E., & Chalupa, L.M. (2002). Depletion of cholinergic amacrine cells by a novel immunotoxin does not perturb the formation of segregated on and off cone bipolar cell projections. Journal of Neuroscience 22, 2265–2273.Google Scholar
Gunhan-Agar, E., Kahn, D., & Chalupa, L.M. (2000). Segregation of on and off bipolar cell axonal arbors in the absence of retinal ganglion cells. Journal of Neuroscience 20, 306–314.Google Scholar
Job, C. & Lagnado, L. (1998). Calcium and protein kinase C regulate the actin cytoskeleton in the synaptic terminal of retinal bipolar cells. Journal of Cell Biology 143, 1661–1672.CrossRefGoogle Scholar
Jontes, J.D. & Smith, S.J. (2000). Filopodia, spines, and the generation of synaptic diversity. Neuron 27, 11–14.CrossRefGoogle Scholar
Kay, J.N., Roeser, T., Mumm, J.S., Godinho, L., Mrejeru, A., Wong, R.O.L., & Baier, H. (2004). Transient requirement for ganglion cells during assembly of retinal synaptic layers. Development 131, 1331–1342.Google Scholar
Koster, R.W. & Fraser, S.E. (2001). Tracing transgene expression in living zebrafish embryos. International Journal of Developmental Biology 233, 329–346.CrossRefGoogle Scholar
Lohmann, C., Mumm, J.S., Morgan, J., Godinho, L., Schroeter, E.H., Stacy, R., Wong, W.T., Oakley, D., & Wong, R.O.L. (2005). Imaging the developing retina. In Imaging in Neuroscience and Development, eds. Yuste, R. & Konnerth, A., pp. 171–183. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
Miller, E.D., Tran, M.N., Wong, G.K., Oakley, D.M., & Wong, R.O. (1999). Morphological differentiation of bipolar cells in the ferret retina. Visual Neuroscience 16, 1133–1144.CrossRefGoogle Scholar
Morest, D.K. (1970). The pattern of neurogenesis in the retina of the rat. Zeitschrift F ür Anatomie Und Entwicklungsgeschichte 131, 45–67.CrossRefGoogle Scholar
Morgan, J., Huckfeldt, R., & Wong, R.O. (2005). Imaging techniques in retinal research. Experimental Eye Research 80, 297–306.CrossRefGoogle Scholar
Morgan, J.L., Dhingra, A., Vardi, N., & Wong, R.O. (2006). Axons and dendrites originate from neuroepithelial-like processes of retinal bipolar cells. Nature Neuroscience 9, 85–92.CrossRefGoogle Scholar
Mumm, J.S., Godinho, L., Morgan, J.L., Oakley, D.M., Schroeter, E.H., & Wong, R.O. (2005). Laminar circuit formation in the vertebrate retina. Progress in Brain Research 147, 155–169.CrossRefGoogle Scholar
Nishimura, Y. & Rakic, P. (1987). Development of the rhesus monkey retina: II. A three-dimensional analysis of the sequences of synaptic combinations in the inner plexiform layer. Journal of Comparative Neurology 262, 290–313.Google Scholar
Olney, J.W. (1968). Centripetal sequence of appearance of receptor-bipolar synaptic structures in developing mouse retina. Nature 218, 281–282.CrossRefGoogle Scholar
Pusch, C.M., Zeitz, C., Brandau, O., Pesch, K., Achatz, H., Feil, S., Scharfe, C., Maurer, J., Jacobi, F.K., Pinckers, A., Andreasson, S., Hardcastle, A., Wissinger, B., Berger, W., & Meindl, A. (2000). The complete form of X-linked congenital stationary night blindness is caused by mutations in a gene encoding a leucine-rich repeat protein. Nature Genetics 26, 324–327.Google Scholar
Quesada, A. & Genis-Galvez, J.M. (1985). Morphological and structural study of Landolt's club in the chick retina. Journal of Morphology 184, 205–214.CrossRefGoogle Scholar
Quesada, A., Prada, F., Armengol, J.A., & Genis-Galvez, J.M. (1981). Early morphological differentiation of the bipolar neurons in the chick retina. A Golgi analysis. Anatomia Histologia Embryologia 10, 328–341.CrossRefGoogle Scholar
Reese, B.E., Raven, M.A., Giannotti, K.A., & Johnson, P.T. (2001). Development of cholinergic amacrine cell stratification in the ferret retina and the effects of early excitotoxic ablation. Visual Neuroscience 18, 559–570.CrossRefGoogle Scholar
Ren, J.Q., McCarthy, W.R., Zhang, H., Adolph, A.R., & Li, L. (2002). Behavioral visual responses of wild-type and hypopigmented zebrafish. Visional Research 42, 293–299.CrossRefGoogle Scholar
Rowan, S. & Cepko, C.L. (2005). A POU factor binding site upstream of the Chx10 homeobox gene is required for Chx10 expression in subsets of retinal progenitor cells and bipolar cells. Developmental Biology 281, 240–255.CrossRefGoogle Scholar
Scheer, N., Groth, A., Hans, S., & Campos-Ortega, J.A. (2001). An instructive function for Notch in promoting gliogenesis in the zebrafish retina. Development 128, 1099–1107.Google Scholar
Schmitt, E.A. & Dowling, J.E. (1999). Early retinal development in the zebrafish, Danio rerio: Light and electron microscopic analyses. Journal of Comparative Neurology 404, 515–536.3.0.CO;2-A>CrossRefGoogle Scholar
Sherry, D.M., Wang, M.M., Bates, J., & Frishman, L.J. (2003). Expression of vesicular glutamate transporter 1 in the mouse retina reveals temporal ordering in development of rod vs. cone and ON vs. OFF circuits. Journal of Comparative Neurology 465, 480–498.Google Scholar
Sherry, D.M. & Yazulla, S. (1993). Goldfish bipolar cells and axon terminal patterns: A Golgi study. Journal of Comparative Neurology 329, 188–200.CrossRefGoogle Scholar
Wassle, H. (2004). Parallel processing in the mammalian retina. Nature Reviews of Neuroscience 5, 747–757.CrossRefGoogle Scholar
Westerfield, M. (2000). The Zebrafish Book. Eugene, OR: University of Oregon Press.
Wong, K.Y., Cohen, E.D., & Dowling, J.E. (2005). Retinal bipolar cell input mechanisms in giant danio. II. Patch-clamp analysis of ON bipolar cells. Journal of Neurophysiology 93, 94–107.Google Scholar
Wong, K.Y. & Dowling, J.E. (2005). Retinal bipolar cell input mechanisms in giant danio. III. ON-OFF bipolar cells and their color-opponent mechanisms. Journal of Neurophysiology 94, 265–272.Google Scholar
Wong, W.T. & Wong, R.O. (2000). Rapid dendritic movements during synapse formation and rearrangement. Current Opinion in Neurobiology 10, 118–124.CrossRefGoogle Scholar
Yazulla, S. & Studholme, K.M. (1992). Light-dependent plasticity of the synaptic terminals of Mb bipolar cells in goldfish retina. Journal of Neurophysiology 320, 521–530.Google Scholar
Yazulla, S. & Studholme, K.M. (2001). Neurochemical anatomy of the zebrafish retina as determined by immunocytochemistry. Journal of Neurocytology 30, 551–592.CrossRefGoogle Scholar
Ziv, N.E. & Smith, S.J. (1996). Evidence for a role of dendritic filopodia in synaptogenesis and spine formation. Neuron 17, 91–102.CrossRefGoogle Scholar

Supplemental movie 1

High magnification serial confocal sections (0.5 Μm steps) through the IPL of a 6 dpf nyx::MYFP fish.
Axon terminals display many filopodia but contain a core within which YFP is absent. Scale bar = 5Μm.

Download Supplemental movie 1(Video)
Video 1.1 MB

Supplemental movie 2

Time-lapse series of an individual axon terminal from 7 dpf nyx::MYFP fish (15 minute intervals), showing rapid extension and retraction of filopodia in an immature terminal. Scale bar = 5 Μm.

Download Supplemental movie 2(Video)
Video 60.4 KB