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Neuron. 2018 Jan 17;97(2):326-340.e4. doi: 10.1016/j.neuron.2017.12.028.

Sonic Hedgehog Is a Remotely Produced Cue that Controls Axon Guidance Trans-axonally at a Midline Choice Point.

Author information

1
Montréal Clinical Research Institute (IRCM), 110 Pine West Ave., Montréal, QC H2W 1R7, Canada, McGill University, Montréal, QC H3A 2B2, Canada; Department of Biology, McGill University, Montréal, QC H3A 2B2, Canada.
2
Montréal Clinical Research Institute (IRCM), 110 Pine West Ave., Montréal, QC H2W 1R7, Canada, McGill University, Montréal, QC H3A 2B2, Canada.
3
Montréal Clinical Research Institute (IRCM), 110 Pine West Ave., Montréal, QC H2W 1R7, Canada, McGill University, Montréal, QC H3A 2B2, Canada; Integrated Program in Neuroscience, McGill University, Montréal, QC H3A 2B2, Canada.
4
RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
5
Montréal Clinical Research Institute (IRCM), 110 Pine West Ave., Montréal, QC H2W 1R7, Canada, McGill University, Montréal, QC H3A 2B2, Canada; Department of Biology, McGill University, Montréal, QC H3A 2B2, Canada; Integrated Program in Neuroscience, McGill University, Montréal, QC H3A 2B2, Canada; Department of Medicine, University of Montréal, Montréal, QC H3T 1J4, Canada. Electronic address: frederic.charron@ircm.qc.ca.

Abstract

At the optic chiasm choice point, ipsilateral retinal ganglion cells (RGCs) are repelled away from the midline by guidance cues, including Ephrin-B2 and Sonic Hedgehog (Shh). Although guidance cues are normally produced by cells residing at the choice point, the mRNA for Shh is not found at the optic chiasm. Here we show that Shh protein is instead produced by contralateral RGCs at the retina, transported anterogradely along the axon, and accumulates at the optic chiasm to repel ipsilateral RGCs. In vitro, contralateral RGC axons, which secrete Shh, repel ipsilateral RGCs in a Boc- and Smo-dependent manner. Finally, knockdown of Shh in the contralateral retina causes a decrease in the proportion of ipsilateral RGCs in a non-cell-autonomous manner. These findings reveal a role for axon-axon interactions in ipsilateral RGC guidance, and they establish that remotely produced cues can act at axon guidance midline choice points.

KEYWORDS:

Shh; axon guidance; axon-axon interaction; choice point; guidance cue; ipsilateral; midline; optic chiasm; retinal ganglion cell

PMID:
29346753
DOI:
10.1016/j.neuron.2017.12.028
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