Article | Published:

Axons and dendrites originate from neuroepithelial-like processes of retinal bipolar cells

Nature Neuroscience volume 9, pages 8592 (2006) | Download Citation

Subjects

Abstract

The cellular mechanisms underlying axogenesis and dendritogenesis are not completely understood. The axons and dendrites of retinal bipolar cells, which contact their synaptic partners within specific laminae in the inner and outer retina, provide a good system for exploring these issues. Using transgenic mice expressing enhanced green fluorescent protein (GFP) in a subset of bipolar cells, we determined that axonal and dendritic arbors of these interneurons develop directly from apical and basal processes attached to the outer and inner limiting membranes, respectively. Selective stabilization of processes contributed to stratification of axonal and dendritic arbors within the appropriate synaptic layer. This unusual mode of axogenesis and dendritogenesis from neuroepithelial-like processes may act to preserve neighbor-neighbor relationships in synaptic wiring between the outer and inner retina.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    & Experimental observations on the development of polarity by hippocampal neurons in culture. J. Cell Biol. 108, 1507–1516 (1989).

  2. 2.

    & Neuronal polarity. Annu. Rev. Neurosci. 17, 267–310 (1994).

  3. 3.

    , & Hippocampal neuronal polarity specified by spatially localized mPar3/mPar6 and PI 3-kinase activity. Cell 112, 63–75 (2003).

  4. 4.

    & In vitro analysis of the origin, migratory behavior, and maturation of cortical pyramidal cells. J. Comp. Neurol. 454, 1–14 (2002).

  5. 5.

    & Precursors of neurons, neuroglia, and ependymal cells in the CNS: what are they? Where are they from? How do they get where they are going? Glia 43, 6–18 (2003).

  6. 6.

    & Migration and differentiation of neurons in the retina and optic tectum of the chick. Exp. Neurol. 134, 13–24 (1995).

  7. 7.

    et al. Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4-phosphonobutyrate. J. Biol. Chem. 268, 11868–11873 (1993).

  8. 8.

    et al. Developmentally regulated postsynaptic localization of a metabotropic glutamate receptor in rat rod bipolar cells. Cell 77, 361–369 (1994).

  9. 9.

    & ON cone bipolar cells in rat express the metabotropic receptor mGluR6. Vis. Neurosci. 14, 789–794 (1997).

  10. 10.

    Bipolar cells use kainate and AMPA receptors to filter visual information into separate channels. Neuron 28, 847–856 (2000).

  11. 11.

    , & Rod bipolar cells in the mammalian retina show protein kinase C-like immunoreactivity. J. Comp. Neurol. 301, 433–442 (1990).

  12. 12.

    et al. Morphological characterization of the retina of the CNGA3−/−Rho−/− mutant mouse lacking functional cones and rods. Invest. Ophthalmol. Vis. Sci. 45, 2039–2048 (2004).

  13. 13.

    , & Coexpression patterns of mGluR mRNAs in rat retinal ganglion cells: a single-cell RT-PCR study. Invest. Ophthalmol. Vis. Sci. 41, 314–319 (2000).

  14. 14.

    , , , & Cell fate determination in the vertebrate retina. Proc. Natl. Acad. Sci. USA 93, 589–595 (1996).

  15. 15.

    & Synaptic contacts between an identified type of ON cone bipolar cell and ganglion cells in the mouse retina. Eur. J. Neurosci. 21, 1257–1270 (2005).

  16. 16.

    , & Directing gene expression to gustducin-positive taste receptor cells. J. Neurosci. 19, 5802–5809 (1999).

  17. 17.

    , , , & Axon branch removal at developing synapses by axosome shedding. Neuron 44, 651–661 (2004).

  18. 18.

    , & The establishment of polarity by hippocampal neurons in culture. J. Neurosci. 8, 1454–1468 (1988).

  19. 19.

    & Rapid changes in the distribution of GAP-43 correlate with the expression of neuronal polarity during normal development and under experimental conditions. J. Cell Biol. 110, 1319–1331 (1990).

  20. 20.

    & Ganglion cell neurogenesis, migration and early differentiation in the chick retina. Neuroscience 58, 399–409 (1994).

  21. 21.

    et al. Centrosome localization determines neuronal polarity. Nature 436, 704–708 (2005).

  22. 22.

    , , & Early morphological differentiation of the bipolar neurons in the chick retina. A Golgi analysis. Anat. Histol. Embryol. 10, 328–341 (1981).

  23. 23.

    & Morphological and structural study of Landolt's club in the chick retina. J. Morphol. 184, 205–214 (1985).

  24. 24.

    & Genetic analysis of the homeodomain transcription factor Chx10 in the retina using a novel multifunctional BAC transgenic mouse reporter. Dev. Biol. 271, 388–402 (2004).

  25. 25.

    Studies on Vertebrate Neurogenesis (Thomas, Springfield, Illinois, 1960).

  26. 26.

    & Morphogenesis of retinal ganglion cells: a model of dendritic, mosaic, and foveal development. Perspect. Dev. Neurobiol. 3, 177–194 (1996).

  27. 27.

    , , & Distinct migratory behavior of early- and late-born neurons derived from the cortical ventricular zone. J. Comp. Neurol. 479, 1–14 (2004).

  28. 28.

    , & Computational model of the on-alpha ganglion cell receptive field based on bipolar cell circuitry. Proc. Natl. Acad. Sci. USA 89, 236–240 (1992).

  29. 29.

    & Microcircuitry related to the receptive field center of the on-beta ganglion cell. J. Neurophysiol. 65, 352–359 (1991).

  30. 30.

    & Demonstration of cell types among cone bipolar neurons of cat retina. Phil. Trans. R. Soc.B 330, 305–321 (1990).

  31. 31.

    , & In vivo imaging of synapse formation on a growing dendritic arbor. Nat. Neurosci. 7, 254–260 (2004).

  32. 32.

    & Developmental relationship between cholinergic amacrine cell processes and ganglion cell dendrites of the mouse retina. J. Comp. Neurol. 456, 154–166 (2003).

  33. 33.

    et al. Transient requirement for ganglion cells during assembly of retinal synaptic layers. Development 131, 1331–1342 (2004).

  34. 34.

    , & Segregation of on and off bipolar cell axonal arbors in the absence of retinal ganglion cells. J. Neurosci. 20, 306–314 (2000).

  35. 35.

    , , & Mechanisms of neuronal polarity. Curr. Opin. Neurobiol. 7, 599–604 (1997).

  36. 36.

    et al. The reelin pathway modulates the structure and function of retinal synaptic circuitry. Neuron 31, 929–941 (2001).

  37. 37.

    , , & Localization of mGluR6 to dendrites of ON bipolar cells in primate retina. J. Comp. Neurol. 423, 402–412 (2000).

  38. 38.

    , & Developmental loss of synchronous spontaneous activity in the mouse retina is independent of visual experience. J. Neurosci. 23, 2851–2860 (2003).

  39. 39.

    et al. Imaging the developing retina. in Imaging in Neuroscience and Development. (eds. Yuste, R. & Konnerth, A.) 159–170 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 2005).

Download references

Acknowledgements

We thank R.F. Margolskee and R.H. Masland for providing the GUS8.4-GFP mice. This work is supported by grants from the US National Institutes of Health (EY10699 to R.O.L.W. and EY11105 to N.V.) and the Bakewell and Alafi Neuroimaging Laboratories.

Author information

Author notes

    • Josh L Morgan
    •  & Anuradha Dhingra

    These authors contributed equally to this work.

Affiliations

  1. Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.

    • Josh L Morgan
    •  & Rachel O L Wong
  2. Department of Neuroscience, University of Pennsylvania School of Medicine, 123 Anatomy/Chemistry Building, Philadelphia, Pennsylvania 19104–6058, USA.

    • Anuradha Dhingra
    •  & Noga Vardi

Authors

  1. Search for Josh L Morgan in:

  2. Search for Anuradha Dhingra in:

  3. Search for Noga Vardi in:

  4. Search for Rachel O L Wong in:

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Rachel O L Wong.

Supplementary information

Videos

  1. 1.

    Supplementary Video 1

    3D rotation of a confocal stack from a P3 Grm6-GFP retinal cross-section. In this region, a GFP positive bipolar axon terminal can be distinguished from the relatively dimmer IPL processes of neighboring amacrine cells and RGCs upon rotation of the image stack. For example, a GFP-labeled process (arrow 2) that appears close to the bipolar cell axon (arrow 1) in the initial frame, clearly moves apart from the axon in subsequent frames when the stack is rotated. Here, we have also highlighted the bipolar axon and its fine terminals in white using the 3D segmentation program in Amira, to provide a high contrast view of the axon. Inner nuclear layer (INL), inner plexiform layer (IPL), ganglion cell layer (GCL).

  2. 2.

    Supplementary Video 2

    Time-lapse showing process motility in some axonal arbors of P6 bipolar cells in the Grm6-GFP mouse retina (confocal image stacks, 7 time frames, 30 min between frames). Note extensions and retractions that are particularly evident in the bright axon.

  3. 3.

    Supplementary Video 3

    3D confocal reconstruction of P10 Grm6-GFP retina showing extensions of bipolar cell axons into the ganglion cell layer (GCL), some of which retracted during the recording period. The boundaries of the inner plexiform layer (IPL) and inner nuclear layer (INL) are provided. In the first segment of the movie, the image stack is cropped and rotated in 3D to provide a clearer view of the morphology of the processes within the GCL. In the second segment, the retraction of an axonal terminal (middle of the field of view) in the GCL is apparent in a zoomed up view of this region (7 time points, 20 min between frames).

  4. 4.

    Supplementary Video 4

    Movie showing process extension and retraction from the apical process of the cell shown in Fig. 6b (7 frames, 20 min between frames). Outer nuclear layer (ONL), outer plexiform layer (OPL); inner nuclear layer (INL).

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nn1615

Further reading