Secreted frizzled related proteins modulate pathfinding and fasciculation of mouse retina ganglion cell axons by direct and indirect mechanisms

Retina ganglion cell (RGC) axons grow along a stereotyped pathway undergoing coordinated rounds of fasciculation and defasciculation, which are critical to establishing proper eye– brain connections. How this coordination is achieved is poorly understood, but shedding of guidance cues by metalloprot...

Descripción completa

Detalles Bibliográficos
Autores: Marcos, Séverine, Nieto-Lopez, Francisco, Sandonìs, Africa, Cardozo, Marcos Julian, Di Marco, Fabiana, Esteve, Pilar, Bovolenta, Paola
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/667266
Acceso en línea:http://hdl.handle.net/10486/667266
https://dx.doi.org/10.1523/JNEUROSCI.3304-13.2015
Access Level:acceso abierto
Palabra clave:Axon guidance
Metalloproteinase
Optic chiasm
Optic disc
Sfrp
Visual pathway
Biología y Biomedicina / Biología
id ES_bc49476085f930b2ca7a41aeef582b85
oai_identifier_str oai:repositorio.uam.es:10486/667266
network_acronym_str ES
network_name_str España
repository_id_str
spelling Secreted frizzled related proteins modulate pathfinding and fasciculation of mouse retina ganglion cell axons by direct and indirect mechanismsMarcos, SéverineNieto-Lopez, FranciscoSandonìs, AfricaCardozo, Marcos JulianDi Marco, FabianaEsteve, PilarBovolenta, PaolaAxon guidanceMetalloproteinaseOptic chiasmOptic discSfrpVisual pathwayBiología y Biomedicina / BiologíaRetina ganglion cell (RGC) axons grow along a stereotyped pathway undergoing coordinated rounds of fasciculation and defasciculation, which are critical to establishing proper eye– brain connections. How this coordination is achieved is poorly understood, but shedding of guidance cues by metalloproteinases is emerging as a relevant mechanism. Secreted Frizzled Related Proteins (Sfrps) are multifunctional proteins, which, among others, reorient RGC growth cones by regulating intracellular second messengers, and interact with Tolloid and ADAM metalloproteinases, thereby repressing their activity. Here, we show that the combination of these two functions well explain the axon guidance phenotype observed in Sfrp1 and Sfrp2 single and compound mouse mutant embryos, in whichRGCaxons make subtle but significant mistakes during their intraretinal growth and inappropriately defasciculate along their pathway. The distribution of Sfrp1 and Sfrp2 in the eye is consistent with the idea that Sfrp1/2 normally constrain axon growth into the fiber layer and the optic disc. Disheveled axon growth instead seems linked to Sfrp-mediated modulation of metalloproteinase activity. Indeed, retinal explants from embryos with different Sfrp-null alleles or explants overexpressing ADAM10 extend axons with a disheveled appearance, which is reverted by the addition of Sfrp1 or an ADAM10-specific inhibitor. This mode of growth is associated with an abnormal proteolytic processing of L1 and N-cadherin, two ADAM10 substrates previously implicated in axon guidance.Wethus propose that Sfrps contribute to coordinate visual axon growth with a dual mechanism: by directly signaling at the growth cone and by regulating the processing of other relevant cuesThis work was supported by the Spanish MINECO (Grants BFU2010-16031 and BFU2013-43213-P), Comunidad Autónoma de Madrid (Grant S2010/BMD-2315) Cost Action BM1001 Brain ECM in Health and Disease, an institutional grant from the Fundación Ramón Areces and Centro de Investigación Biomédica en Red de Enfermedades Raras (P.B.). F.N.-L. and M.J.C. were supported by a FPU and FPI fellowship from the Spanish Government, respectively. We thank F. Murakami, L. Erskine, A. Chedotal, A. Ludwig, and V.P. Lemmon for reagentsSociety for NeuroscienceFacultad de Ciencias20152015-01-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/667266https://dx.doi.org/10.1523/JNEUROSCI.3304-13.2015reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6672662026-06-23T12:46:27Z
dc.title.none.fl_str_mv Secreted frizzled related proteins modulate pathfinding and fasciculation of mouse retina ganglion cell axons by direct and indirect mechanisms
title Secreted frizzled related proteins modulate pathfinding and fasciculation of mouse retina ganglion cell axons by direct and indirect mechanisms
spellingShingle Secreted frizzled related proteins modulate pathfinding and fasciculation of mouse retina ganglion cell axons by direct and indirect mechanisms
Marcos, Séverine
Axon guidance
Metalloproteinase
Optic chiasm
Optic disc
Sfrp
Visual pathway
Biología y Biomedicina / Biología
title_short Secreted frizzled related proteins modulate pathfinding and fasciculation of mouse retina ganglion cell axons by direct and indirect mechanisms
title_full Secreted frizzled related proteins modulate pathfinding and fasciculation of mouse retina ganglion cell axons by direct and indirect mechanisms
title_fullStr Secreted frizzled related proteins modulate pathfinding and fasciculation of mouse retina ganglion cell axons by direct and indirect mechanisms
title_full_unstemmed Secreted frizzled related proteins modulate pathfinding and fasciculation of mouse retina ganglion cell axons by direct and indirect mechanisms
title_sort Secreted frizzled related proteins modulate pathfinding and fasciculation of mouse retina ganglion cell axons by direct and indirect mechanisms
dc.creator.none.fl_str_mv Marcos, Séverine
Nieto-Lopez, Francisco
Sandonìs, Africa
Cardozo, Marcos Julian
Di Marco, Fabiana
Esteve, Pilar
Bovolenta, Paola
author Marcos, Séverine
author_facet Marcos, Séverine
Nieto-Lopez, Francisco
Sandonìs, Africa
Cardozo, Marcos Julian
Di Marco, Fabiana
Esteve, Pilar
Bovolenta, Paola
author_role author
author2 Nieto-Lopez, Francisco
Sandonìs, Africa
Cardozo, Marcos Julian
Di Marco, Fabiana
Esteve, Pilar
Bovolenta, Paola
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Facultad de Ciencias
dc.subject.none.fl_str_mv Axon guidance
Metalloproteinase
Optic chiasm
Optic disc
Sfrp
Visual pathway
Biología y Biomedicina / Biología
topic Axon guidance
Metalloproteinase
Optic chiasm
Optic disc
Sfrp
Visual pathway
Biología y Biomedicina / Biología
description Retina ganglion cell (RGC) axons grow along a stereotyped pathway undergoing coordinated rounds of fasciculation and defasciculation, which are critical to establishing proper eye– brain connections. How this coordination is achieved is poorly understood, but shedding of guidance cues by metalloproteinases is emerging as a relevant mechanism. Secreted Frizzled Related Proteins (Sfrps) are multifunctional proteins, which, among others, reorient RGC growth cones by regulating intracellular second messengers, and interact with Tolloid and ADAM metalloproteinases, thereby repressing their activity. Here, we show that the combination of these two functions well explain the axon guidance phenotype observed in Sfrp1 and Sfrp2 single and compound mouse mutant embryos, in whichRGCaxons make subtle but significant mistakes during their intraretinal growth and inappropriately defasciculate along their pathway. The distribution of Sfrp1 and Sfrp2 in the eye is consistent with the idea that Sfrp1/2 normally constrain axon growth into the fiber layer and the optic disc. Disheveled axon growth instead seems linked to Sfrp-mediated modulation of metalloproteinase activity. Indeed, retinal explants from embryos with different Sfrp-null alleles or explants overexpressing ADAM10 extend axons with a disheveled appearance, which is reverted by the addition of Sfrp1 or an ADAM10-specific inhibitor. This mode of growth is associated with an abnormal proteolytic processing of L1 and N-cadherin, two ADAM10 substrates previously implicated in axon guidance.Wethus propose that Sfrps contribute to coordinate visual axon growth with a dual mechanism: by directly signaling at the growth cone and by regulating the processing of other relevant cues
publishDate 2015
dc.date.none.fl_str_mv 2015
2015-01-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/667266
https://dx.doi.org/10.1523/JNEUROSCI.3304-13.2015
url http://hdl.handle.net/10486/667266
https://dx.doi.org/10.1523/JNEUROSCI.3304-13.2015
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869418100056653824
score 15,300724

Similares en LA Referencia