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, Arturo José Valiño, Salvador Sala, Ronan DaSilva, Artur Kania, Víctor Borrell, Luis M. Martinez, Lynda Erskine, Eloisa Herrera (Corresponding Author)

Research output: Contribution to journalArticle

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Abstract

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
Volume29
Issue number7
Early online date21 Mar 2019
DOIs
Publication statusPublished - Apr 2019

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retina
Retina
Retinal Ganglion Cells
Diencephalon
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Labeling
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Theoretical Models
mathematical models
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receptors
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Keywords

  • retino-retinal connectivity
  • RGCs
  • axon guidance
  • Unc5c
  • Netrin1
  • visual pathway
  • visual axon refinement
  • synchronization of retinal activity
  • spontaneous activity
  • retinal waves
  • UNC-5
  • AXON GUIDANCE
  • OPTIC-NERVE REGENERATION
  • PATTERNS
  • MIDLINE
  • RETINOGENICULATE
  • GANGLION-CELLS
  • GROWTH
  • NEURAL ACTIVITY
  • EXPRESSION

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Murcia-Belmonte, V., Coca, Y., Vegar, C., Negueruela, S., de Juan, C., Valiño, A. J., ... Herrera, E. (2019). A retino-retinal projection guided by Unc5c emerged in species with retinal waves. Current Biology, 29(7), 1149-1160. https://doi.org/10.1016/j.cub.2019.02.052

A retino-retinal projection guided by Unc5c emerged in species with retinal waves. / Murcia-Belmonte, Verónica; Coca, Yaiza; Vegar, Celia; Negueruela, Santiago; de Juan, Camino; Valiño, Arturo José ; Sala, Salvador; DaSilva, Ronan; Kania, Artur; Borrell, Víctor; Martinez, Luis M.; Erskine, Lynda; Herrera, Eloisa (Corresponding Author).

In: Current Biology, Vol. 29, No. 7, 04.2019, p. 1149-1160.

Research output: Contribution to journalArticle

Murcia-Belmonte, V, Coca, Y, Vegar, C, Negueruela, S, de Juan, C, Valiño, AJ, Sala, S, DaSilva, R, Kania, A, Borrell, V, Martinez, LM, Erskine, L & Herrera, E 2019, 'A retino-retinal projection guided by Unc5c emerged in species with retinal waves', Current Biology, vol. 29, no. 7, pp. 1149-1160. https://doi.org/10.1016/j.cub.2019.02.052
Murcia-Belmonte V, Coca Y, Vegar C, Negueruela S, de Juan C, Valiño AJ et al. A retino-retinal projection guided by Unc5c emerged in species with retinal waves. Current Biology. 2019 Apr;29(7):1149-1160. https://doi.org/10.1016/j.cub.2019.02.052
Murcia-Belmonte, Verónica ; Coca, Yaiza ; Vegar, Celia ; Negueruela, Santiago ; de Juan, Camino ; Valiño, Arturo José ; Sala, Salvador ; DaSilva, Ronan ; Kania, Artur ; Borrell, Víctor ; Martinez, Luis M. ; Erskine, Lynda ; Herrera, Eloisa. / A retino-retinal projection guided by Unc5c emerged in species with retinal waves. In: Current Biology. 2019 ; Vol. 29, No. 7. pp. 1149-1160.
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abstract = "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 patternthat 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 ofthe R-R projection and suggest an important role for these projections in visual mapping to ensure congruent bilateral refinement.",
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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.",
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AU - Murcia-Belmonte, Verónica

AU - Coca, Yaiza

AU - Vegar, Celia

AU - Negueruela, Santiago

AU - de Juan, Camino

AU - Valiño, Arturo José

AU - Sala, Salvador

AU - DaSilva, Ronan

AU - Kania, Artur

AU - Borrell, Víctor

AU - Martinez, Luis M.

AU - Erskine, Lynda

AU - Herrera, Eloisa

N1 - 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.

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N2 - 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 patternthat 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 ofthe R-R projection and suggest an important role for these projections in visual mapping to ensure congruent bilateral refinement.

AB - 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 patternthat 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 ofthe R-R projection and suggest an important role for these projections in visual mapping to ensure congruent bilateral refinement.

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KW - synchronization of retinal activity

KW - spontaneous activity

KW - retinal waves

KW - UNC-5

KW - AXON GUIDANCE

KW - OPTIC-NERVE REGENERATION

KW - PATTERNS

KW - MIDLINE

KW - RETINOGENICULATE

KW - GANGLION-CELLS

KW - GROWTH

KW - NEURAL ACTIVITY

KW - EXPRESSION

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