A Retino-retinal Projection Guided by Unc5c Emerged in Species with Retinal Waves

Verónica Murcia-Belmonte, Yaiza Coca, Celia Vegar, Santiago Negueruela, Camino de Juan Romero, Arturo José Valiño, Salvador Sala, Ronan DaSilva, Artur Kania, Víctor Borrell, Luis M. Martinez, Lynda Erskine, Eloisa Herrera* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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The existence of axons extending from one retina to the other has been reported during perinatal development in different vertebrates. However, it has been thought that these axons are either a labelling artefact or misprojections. Here, we show unequivocally that a small subset of retinal ganglion cells (RGCs) project to the opposite retina and that the guidance receptor Unc5c, expressed in the retinal region where the retinal-retinal (R-R) RGCs are located, is necessary and sufficient to guide axons to the opposite retina. In addition, Netrin1, an Unc5c ligand, is expressed in the ventral diencephalon in a pattern
that is consistent with impeding the growth of Unc5c-positive retinal axons into the brain. We also have generated a mathematical model to explore the formation of retinotopic maps in the presence and absence of a functional connection between both eyes. This model predicts that a R-R connection is required for the bilateral coordination of axonal refinement in species where refinement depends upon spontaneous retinal waves. Consistent with this idea, the retinal expression of Unc5c correlates with the existence and size of a R-R projection in different species and with the extent of axonal refinement in visual targets. These findings demonstrate that active guidance drives the formation of
the R-R projection and suggest an important role for these projections in visual mapping to ensure congruent bilateral refinement.
Original languageEnglish
Pages (from-to)1149-1160
Number of pages12
JournalCurrent Biology
Issue number7
Early online date21 Mar 2019
Publication statusPublished - 1 Apr 2019

Bibliographical note

We thank D Baeza and M Herrera for mouse breeding, genotyping and help in in utero electroporation experiments and E Llorens and J Mullet for technical help in experiments involving ferrets. We also thank A Barco for discussion and comments on the manuscript. The laboratory of EH is funded with the following grants: (BFU2016-77605 from the National Grant Research Program, PROMETEO Program (2016/026) from Generalitat Valenciana, (PCIN2015-192-C02-02 from ERA-Net Program) and (ERC282329 from the European Research Council). Work in the laboratory of LMM and SS was supported by the National Grant Research Program (Grant BFU2014-58776-r), cofinanced by the European Regional Development Fund (ERDF). VMB holds a postdoctoral contract from the Regional Government. AJV is the recipient of a FPI fellowship from the National Grant Research Program. We also acknowledge the financial support received from the “Severo Ochoa” Program for Centers of Excellence in R&D (SEV-2013-0317). AK was supported by the Canadian Institutes for Health Research Operating Grants MOP-77556 and MOP-97758, as well as Brain Canada, Canadian Foundation for Innovation, and the W. Garfield Weston Foundation.


  • retino-retinal connectivity
  • RGCs
  • axon guidance
  • Unc5c
  • Netrin1
  • visual pathway
  • visual axon refinement
  • synchronization of retinal activity
  • spontaneous activity
  • retinal waves


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