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Transient neurites of retinal horizontal cells exhibit columnar tiling via homotypic interactions

Nature Neuroscience volume 12, pages 35–43 (2009)Cite this article

Abstract

Sensory neurons with common functions are often nonrandomly arranged and form dendritic territories that show little overlap, or tiling. Repulsive homotypic interactions underlie such patterns in cell organization in invertebrate neurons. It is unclear how dendro-dendritic repulsive interactions can produce a nonrandom distribution of cells and their spatial territories in mammalian retinal horizontal cells, as mature horizontal cell dendrites overlap substantially. By imaging developing mouse horizontal cells, we found that these cells transiently elaborate vertical neurites that form nonoverlapping columnar territories on reaching their final laminar positions. Targeted cell ablation revealed that the vertical neurites engage in homotypic interactions that result in tiling of neighboring cells before the establishment of their dendritic fields. This developmental tiling of transient neurites correlates with the emergence of a nonrandom distribution of the cells and could represent a mechanism that organizes neighbor relationships and territories of neurons before circuit assembly.

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Figure 1: Horizontal cells in the G42 retina express GFP.
Figure 2: Positioning of horizontal cells in the correct lamina is accompanied by reorganization of their neurites.
Figure 3: Embryonic horizontal cells show free migration and lateral somal translocation.
Figure 4: Vertical neurites form territories with minimal and stable overlap.
Figure 5: Transient vertical neurites exhibit homotypic interactions.
Figure 6: Homotypic interactions are present between embryonic horizontal cells.
Figure 7: Vertical neurites do not appear to be contacted by cone terminals.

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Acknowledgements

We wish to thank S. Eglen (Cambridge University) and members of the Wong lab for many helpful discussions. This work was supported by US National Institutes of Health grants to R.O.L.W. (EY17101) and J.Z.H., and a National Research Service Award pre-doctoral fellowship to R.M.H.

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Author notes

  1. Timm Schubert and Josh L Morgan: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biological Structure, University of Washington, 1959 NE Pacific Street, Seattle, 98195, Washington, USA

    Rachel M Huckfeldt, Timm Schubert, Josh L Morgan & Rachel O L Wong

  2. Institute of Stem Cell Research, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, Neuherberg, D-85764, Germany

    Leanne Godinho

  3. Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York, 11724, USA

    Graziella Di Cristo & Z Josh Huang

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Contributions

R.M.H. and R.O.L.W. conceived the study and wrote the manuscript. R.O.L.W. supervised the project. R.M.H., T.S., J.L.M. and L.G. carried out the experiments and/or data analysis. J.L.M. wrote the MatLab routines for the analysis. G.D.C. and Z.J.H. provided the G42 mice. All authors contributed to preparation of the manuscript.

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Correspondence to Rachel O L Wong.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–7 (PDF 1500 kb)

Supplementary Video 1

Time-lapse movie of cell shown in Figure 3b. (AVI 740 kb)

Supplementary Video 2

Time course showing extension of neurites into a region where two horizontal cells (grey) were ablated. Note that even after the region was filled in by the neurites of neighboring cells, the arbors of each cell remodeled over time, but formed non-overlapping territories at each time point (compare last two time points at 4.75 h and 8.75 h). (MOV 3801 kb)

Supplementary Video 3

An example showing neurites directed towards the ablation zone in a P3 retina. Time between frames, first post-ablation image captured 10 min after ablation. All other frames are about 1 h apart, except for the last two time points, which were about 2 h apart. Total recording duration following ablation was 10.5 hours. (MOV 3514 kb)

Supplementary Video 4

Example of a large ablation in a P2 retina: a total of 18 cells were ablated within 2 h. We analyzed 20 cells surrounding the ablation zone for cell body movement and movement of the center of mass of their territories. There was a significant inward movement of the cell bodies (sign test, P < 0.001) with an average soma displacement of 5.3 ± 0.8 μm. This gives the impression of a distortion in the matrix of surrounding cells, although some cell bodies clearly did not move, whereas others appeared displaced towards the vacated region. Redirection of neurites towards the ablation zone was, as with other ablations, clearly evident. Post-ablation image acquired at 12 h. (MOV 2048 kb)

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Huckfeldt, R., Schubert, T., Morgan, J. et al. Transient neurites of retinal horizontal cells exhibit columnar tiling via homotypic interactions. Nat Neurosci 12, 35–43 (2009). https://doi.org/10.1038/nn.2236

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