Abstract
The retinotectal projection has long been studied experimentally and theoretically, as a model for the formation of topographic brain maps1,2,3. Neighbouring retinal ganglion cells (RGCs) project their axons to neighbouring positions in the optic tectum, thus re-establishing a continuous neural representation of visual space. Mapping along this axis requires chemorepellent signalling from tectal cells, expressing ephrin-A ligands, to retinal growth cones, expressing EphA receptors4. High concentrations of ephrin A, increasing from anterior to posterior, prevent temporal axons from invading the posterior tectum. However, the force that drives nasal axons to extend past the anterior tectum and terminate in posterior regions remains to be identified. We tested whether axon–axon interactions, such as competition, are required for posterior tectum innervation. By transplanting blastomeres from a wild-type (WT) zebrafish into a lakritz (lak) mutant, which lacks all RGCs5, we created chimaeras with eyes that contained single RGCs. These solitary RGCs often extended axons into the tectum, where they branched to form a terminal arbor. Here we show that the distal tips of these arbors were positioned at retinotopically appropriate positions, ruling out an essential role for competition in innervation of the ephrin-A-rich posterior tectum. However, solitary arbors were larger and more complex than under normal, crowded conditions, owing to a lack of pruning of proximal branches during refinement of the retinotectal projection. We conclude that dense innervation is not required for targeting of retinal axons within the zebrafish tectum but serves to restrict arbor size and shape.
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Acknowledgements
We thank T. Xiao, A. Picker, U. Drescher, K. Haas and H. Cline for reagents and advice, and J. Pinkston-Gosse and members of the Baier laboratory for review of the manuscript. This work was supported by the National Institutes of Health (H.B. and N.J.G.) and a March of Dimes Research Grant (H.B.).
Author Contributions N.J.G., L.M.N. and H.B. devised experiments. N.J.G. performed all transplantation experiments and quantified images. L.M.N. conducted single-cell labelling studies in the tectum. N.J.G. and H.B. wrote the manuscript.
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Supplementary Video
The file contains Supplementary Video S1 with RGC axon pathfinding errors during retinal exit in WTBrn3c:mGFP-≳ lak chimeras. Dorsal confocal stack of 7 dpf WTBrn3c:mGFP-≳ lak chimera with ˜5 RGCs in varying retinal positions projecting axons. One axon (blue arrow), is visible exiting the retina, but peripheral RGC axons meander and branch in aberrant directions (red arrows). Similar errors were seen in 〈5% of WTBrn3c:mGFP-≳ lak chimeras with one or more axons projecting to the tectum. Orientation: nasal up, temporal down. (MOV 10950 kb)
Supplementary Figures
The file contains Supplementary Figures S2, S3: Example quantification of retinal and tectal position in a single chimeric larva and corresponding legend. Frequency of cell types identified by single cell electroporation in WT and lakritz larvae and corresponding legend. (PDF 19634 kb)
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Gosse, N., Nevin, L. & Baier, H. Retinotopic order in the absence of axon competition. Nature 452, 892–895 (2008). https://doi.org/10.1038/nature06816
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DOI: https://doi.org/10.1038/nature06816
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