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

Le, Viet-Hang; Orniacki, Clarisse; Murcia-Belmonte, Verónica; Denti, Laura; Schütz, Dagmar; Stumm, Ralf; Ruhrberg, Christiana; (2024) CXCL12 promotes the crossing of retinal ganglion cell axons at the optic chiasm. Development , 151 (2) , Article dev202446. 10.1242/dev.202446. Green open access

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Abstract

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.

Type: Article
Title: CXCL12 promotes the crossing of retinal ganglion cell axons at the optic chiasm
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/dev.202446
Publisher version: http://dx.doi.org/10.1242/dev.202446
Language: English
Additional information: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Keywords: Axon guidance, Binocular vision, CXCL12, Growth cone, Meninges, Mouse, Optic pathway, Mice, Animals, Retinal Ganglion Cells, Optic Chiasm, Retina, Axons, Diencephalon, Visual Pathways
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10185899
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