Abstract
The mechanisms underlying the precise targeting of tectal layers by ingrowing retinal axons are largely unknown. In zebrafish, individual axons choose one of four retinorecipient layers upon entering the tectum and remain restricted to this layer, despite continual remodeling and shifting of their terminal arbors. In dragnet mutants, by contrast, a large fraction of retinal axons aberrantly trespass between layers or form terminal arbors that span two layers. The dragnet gene, drg, encodes collagen IVα5 (Col4a5), a basement membrane component lining the surface of the tectum. Heparan sulfate proteoglycans (HSPGs) are normally associated with the tectal basement membrane but are dispersed in the dragnet mutant tectum. Zebrafish boxer (extl3) mutants, which are deficient in HSPG synthesis, show laminar targeting defects similar to those in dragnet. Our results show that the collagen IV sheet anchors secreted factors at the surface of the tectum, which serve as guidance cues for retinal axons.
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Acknowledgements
We thank L.F. Reichardt, S. Pleasure, N. Shah, W. Staub and L. Nevin for their advice and comments on this manuscript. M. Berberoglu contributed data to the axon counts in BGUG fish. C.-B. Chien (University of Utah) kindly provided boxer mutants and 10E4 antibody. This work was supported by the US National Institutes of Health (R01-EY013855 and R01-EY012406 to H.B. and a neuroscience postdoctoral training grant fellowship to T.X.) H.B. was further supported by a David and Lucile Packard Fellowship and an Esther and Joseph Klingenstein Fellowship.
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T.X. carried out all the experiments and prepared the figures. H.B. conceived the project and wrote the paper together with T.X.
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Xiao, T., Baier, H. Lamina-specific axonal projections in the zebrafish tectum require the type IV collagen Dragnet. Nat Neurosci 10, 1529–1537 (2007). https://doi.org/10.1038/nn2002
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DOI: https://doi.org/10.1038/nn2002
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