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

doi:10.1016/j.cub.2019.02.052

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 journal › Article › peer-review

14 Citations (Scopus)

14 Downloads (Pure)

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 language	English
Pages (from-to)	1149-1160
Number of pages	12
Journal	Current Biology
Volume	29
Issue number	7
Early online date	21 Mar 2019
DOIs	https://doi.org/10.1016/j.cub.2019.02.052
Publication status	Published - 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.

Keywords

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

Access to Document

10.1016/j.cub.2019.02.052Licence: CC BY-NC-ND

A Retino-retinal Projection Guided by Unc5c Emerged in Species with Retinal Waves
Under a Creative Commons license https://creativecommons.org/licenses/by-nc-nd/4.0/
Final published version, 5.18 MBLicence: CC BY-NC-ND

Cite this

@article{d8a0ec589c1b4f01840d5bbbf9145638,

title = "A Retino-retinal Projection Guided by Unc5c Emerged in Species with Retinal Waves",

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.",

keywords = "retino-retinal connectivity, RGCs, axon guidance, Unc5c, Netrin1, visual pathway, visual axon refinement, synchronization of retinal activity, spontaneous activity, retinal waves",

author = "Ver{\'o}nica Murcia-Belmonte and Yaiza Coca and Celia Vegar and Santiago Negueruela and {de Juan Romero}, Camino and Vali{\~n}o, {Arturo Jos{\'e}} and Salvador Sala and Ronan DaSilva and Artur Kania and V{\'i}ctor Borrell and Martinez, {Luis M.} and Lynda Erskine and Eloisa Herrera",

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.",

year = "2019",

month = apr,

day = "1",

doi = "10.1016/j.cub.2019.02.052",

language = "English",

volume = "29",

pages = "1149--1160",

journal = "Current Biology",

issn = "0960-9822",

publisher = "Cell Press",

number = "7",

}

TY - JOUR

T1 - A Retino-retinal Projection Guided by Unc5c Emerged in Species with Retinal Waves

AU - Murcia-Belmonte, Verónica

AU - Coca, Yaiza

AU - Vegar, Celia

AU - Negueruela, Santiago

AU - de Juan Romero, 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.

PY - 2019/4/1

Y1 - 2019/4/1

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.

KW - retino-retinal connectivity

KW - RGCs

KW - axon guidance

KW - Unc5c

KW - Netrin1

KW - visual pathway

KW - visual axon refinement

KW - synchronization of retinal activity

KW - spontaneous activity

KW - retinal waves

UR - http://www.scopus.com/inward/record.url?scp=85063403736&partnerID=8YFLogxK

UR - http://www.mendeley.com/research/retinoretinal-projection-guided-unc5c-emerged-species-retinal-waves-1

U2 - 10.1016/j.cub.2019.02.052

DO - 10.1016/j.cub.2019.02.052

M3 - Article

C2 - 30905607

SN - 0960-9822

VL - 29

SP - 1149

EP - 1160

JO - Current Biology

JF - Current Biology

IS - 7

ER -

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

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Lynda Erskine

Cite this

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

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Profiles

Lynda Erskine

Cite this