Open Access via the JISC/CUP agreement Funding This work was supported by a University of Aberdeen Elphinstone Scholarship to V.-H.L., a Deutsche Forschungsgemeinschaft grant [TU295/10-1] to R.S. and a Wellcome Trust New Investigator Award [095623/Z/11/Z] to C.R. Open Access funding provided by University of Aberdeen. Deposited in PMC for immediate release.Peer reviewe

Denti, Laura

Erskine, Lynda

Le, Viet Hang

Murcia-Belmonte, Veronica

Orniacki, Clarisse

Ruhrberg, Christiana

Schutz, Dagmar

Stumm, Ralf

Development

English

Binocular vision requires the segregation of retinal ganglion cell (RGC) axons extending from the retina into the ipsilateral and contralateral optic tracts. RGC axon segregation occurs at the optic chiasm, which forms at the ventral diencephalon midline. Using expression analyses, retinal explants and genetically modified mice, we demonstrate that CXCL12 (SDF1) is required for axon segregation at the optic chiasm. CXCL12 is expressed by the meninges bordering the optic pathway, and CXCR4 by both ipsilaterally and contralaterally projecting RGCs. CXCL12 or ventral diencephalon meninges potently promoted axon outgrowth from both ipsilaterally and contralaterally projecting RGCs. Further, a higher proportion of axons projected ipsilaterally in mice lacking CXCL12 or its receptor CXCR4 compared with wild-type mice as a result of misrouting of presumptive contralaterally specified RGC axons. Although RGCs also expressed the alternative CXCL12 receptor ACKR3, the optic chiasm developed normally in mice lacking ACKR3. Our data support a model whereby meningeal-derived CXCL12 helps drive axon growth from CXCR4-expressing RGCs towards the diencephalon midline, enabling contralateral axon growth. These findings further our understanding of the molecular and cellular mechanisms controlling optic pathway development.This work was supported by a University of Aberdeen Elphinstone Scholarship to
V.-H.L., a Deutsche Forschungsgemeinschaft grant [TU295/10-1] to R.S. and a
Wellcome Trust New Investigator Award [095623/Z/11/Z] to C.R.Open Access
funding provided by University of Aberdeen.Peer reviewe

Le, Viet-Hang

Murcia-Belmonte, Verónica

Schütz, Dagmar

Erskine, Andrew

Digital.CSIC

CXCL12 promotes the crossing of retinal ganglion cell axons at the optic chiasm

The Open University

https://aura.abdn.ac.uk/bitstream/2164/22781/1/Le_etal_D_CXCL12_promotes_the_VoR.pdf

CXCL12 promotes the crossing of retinal ganglion cell axons at the optic chiasm

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Digital.CSIC

The Open University