2018
DOI: 10.1016/j.neuron.2017.12.028
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Sonic Hedgehog Is a Remotely Produced Cue that Controls Axon Guidance Trans-axonally at a Midline Choice Point

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, con… Show more

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Cited by 71 publications
(67 citation statements)
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“…In the mouse, approximately 5% of neurons are excluded from the optic chiasm and form an ipsilateral projection in the optic tract (Petros et al, 2008). These ipsilateral axons are repelled by a combination of EphrinB2 expressed by optic chiasm glial cells, and Shh secreted transaxonally by contralateral RGC axons (Peng et al, 2018; Williams et al, 2003). Additional molecular cues govern axonal sorting, targeting of specific retinorecipient regions by subsets of RGC axons, and retinotopic mapping after crossing the chiasm (Feldheim et al, 1998; Hindges et al, 2002; Osterhout et al, 2011; Schmitt et al, 2006; Su et al, 2011; Suetterlin and Drescher, 2014; Sun et al, 2015).…”
Section: Introductionmentioning
confidence: 99%
“…In the mouse, approximately 5% of neurons are excluded from the optic chiasm and form an ipsilateral projection in the optic tract (Petros et al, 2008). These ipsilateral axons are repelled by a combination of EphrinB2 expressed by optic chiasm glial cells, and Shh secreted transaxonally by contralateral RGC axons (Peng et al, 2018; Williams et al, 2003). Additional molecular cues govern axonal sorting, targeting of specific retinorecipient regions by subsets of RGC axons, and retinotopic mapping after crossing the chiasm (Feldheim et al, 1998; Hindges et al, 2002; Osterhout et al, 2011; Schmitt et al, 2006; Su et al, 2011; Suetterlin and Drescher, 2014; Sun et al, 2015).…”
Section: Introductionmentioning
confidence: 99%
“…Their expression may be more restricted later on during RGC development (Pcdh9), or expand to other RGC cell types (Slc6a4; (Assali et al, 2017)). This latter gene is specific to the RGCs that will send their axon to the ipsilateral side of the brain (Koch et al, 2011;Peng et al, 2018). Overall, this analysis showed us that, at this stage (E15), we can recover a large spectrum of differentiation stages of an early retinal cell type.…”
Section: Transcriptional Waves Drive Retinal Ganglion Cell Differentimentioning
confidence: 66%
“…7F), it may also have similar targets and thus play a role in the specification of ipsilateral RGCs. Of note, we fail to detect other genes involved in ipsilateral RGC guidance, such as Boc (Fabre et al, 2010;Peng et al, 2018) andFoxD1 (Carreres et al, 2011, 1;Herrera et al, 2004), in a sufficient number of cells. Along with Zic2, these genes might be either expressed at levels below detection, or be subject to high drop-out events, a caveat of the drop-seq procedure.…”
Section: Identification Of Ipsilateral Rgc Signaturesmentioning
confidence: 67%
“…In addition, the transcription factor Forkhead box D1 was shown to be critical in maintaining iRGCs fate by promoting the expression of Zic2 (Herrera ). In addition to the EphB1/ephrin‐B2 repulsion pathway, another pathway also controls ipsilateral RGC repulsion: Shh is expressed by contralateral RGCs and transported axonally and anterogradely to the optic chiasm (Peng et al ). At the optic chiasm, ipsilateral RGCs, which express the Shh receptor Boc, are repelled by Shh and therefore do not cross the optic chiasm, remaining ipsilateral (Fabre et al ; Peng et al ) (Fig.…”
Section: The Developing Nervous Systemmentioning
confidence: 99%