FGF8 induces formation of an ectopic isthmic organizer and isthmocerebellar development via a repressive effect on Otx2 expression

Beads containing recombinant FGF8 (FGF8-beads) were implanted in the prospective caudal diencephalon or midbrain of chick embryos at stages 9-12. This induced the neuroepithelium rostral and caudal to the FGF8-bead to form two ectopic, mirror-image midbrains. Furthermore, cells in direct contact wit...

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Autores: Martínez, Salvador, Crossley, P. H., Cobos, Inma, Rubenstein, J. L. R., Martin, Gail R.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:1999
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/307893
Acceso en línea:http://hdl.handle.net/10261/307893
Access Level:acceso abierto
Palabra clave:Brain patterning
Cerebellum
Fgf8
Isthmic organizer
Midbrain
Neuromere boundaries
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spelling FGF8 induces formation of an ectopic isthmic organizer and isthmocerebellar development via a repressive effect on Otx2 expressionMartínez, SalvadorCrossley, P. H.Cobos, InmaRubenstein, J. L. R.Martin, Gail R.Brain patterningCerebellumFgf8Isthmic organizerMidbrainNeuromere boundariesBeads containing recombinant FGF8 (FGF8-beads) were implanted in the prospective caudal diencephalon or midbrain of chick embryos at stages 9-12. This induced the neuroepithelium rostral and caudal to the FGF8-bead to form two ectopic, mirror-image midbrains. Furthermore, cells in direct contact with the bead formed an outgrowth that protruded laterally from the neural tube. Tissue within such lateral outgrowths developed proximally into isthmic nuclei and distally into a cerebellum-like structure. These morphogenetic effects were apparently due to FGF8-mediated changes in gene expression in the vicinity of the bead, including a repressive effect on Otx2 and an inductive effect on En1, Fgf8 and Wnt1 expression. The ectopic Fgf8 and Wnt1 expression domains formed nearly complete concentric rings around the FGF8-bead, with the Wnt1 ring outermost. These observations suggest that FGF8 induces the formation of a ring-like ectopic signaling center (organizer) in the lateral wall of the brain, similar to the one that normally encircles the neural tube at the isthmic constriction, which is located at the boundary between the prospective midbrain and hindbrain. This ectopic isthmic organizer apparently sends long-range patterning signals both rostrally and caudally, resulting in the development of the two ectopic midbrains. Interestingly, our data suggest that these inductive signals spread readily in a caudal direction, but are inhibited from spreading rostrally across diencephalic neuromere boundaries. These results provide insights into the mechanism by which FGF8 induces an ectopic organizer and suggest that a negative feedback loop between Fgf8 and Otx2 plays a key role in patterning the midbrain and anterior hindbrain.This work was supported by BIOMED BMH4-CT96-0777 and BIOTECH ERBBIO4-CT96-0146 CE contracts (to S.M.), Fundacion Seneca of Murcia Local Gouvernement FPI grant (to I. C.), Grant RG-41/95 from the Human Frontiers Science Program (to S. M. and J. L. R. R.), research grants from Nina Ireland and NARSAD, and NIH grant KO2 MH01046 (to J. L. R. R.), and NIH grant R01 HD34380 (to G. R. M.).Peer reviewedCompany of BiologistsFundación SénecaGobierno de la Región de MurciaHuman Frontier Science ProgramNational Institutes of Health (US)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320231999info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/307893reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésDevelopmenthttps://doi.org/10.1242/dev.126.6.1189Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3078932026-05-22T06:33:51Z
dc.title.none.fl_str_mv FGF8 induces formation of an ectopic isthmic organizer and isthmocerebellar development via a repressive effect on Otx2 expression
title FGF8 induces formation of an ectopic isthmic organizer and isthmocerebellar development via a repressive effect on Otx2 expression
spellingShingle FGF8 induces formation of an ectopic isthmic organizer and isthmocerebellar development via a repressive effect on Otx2 expression
Martínez, Salvador
Brain patterning
Cerebellum
Fgf8
Isthmic organizer
Midbrain
Neuromere boundaries
title_short FGF8 induces formation of an ectopic isthmic organizer and isthmocerebellar development via a repressive effect on Otx2 expression
title_full FGF8 induces formation of an ectopic isthmic organizer and isthmocerebellar development via a repressive effect on Otx2 expression
title_fullStr FGF8 induces formation of an ectopic isthmic organizer and isthmocerebellar development via a repressive effect on Otx2 expression
title_full_unstemmed FGF8 induces formation of an ectopic isthmic organizer and isthmocerebellar development via a repressive effect on Otx2 expression
title_sort FGF8 induces formation of an ectopic isthmic organizer and isthmocerebellar development via a repressive effect on Otx2 expression
dc.creator.none.fl_str_mv Martínez, Salvador
Crossley, P. H.
Cobos, Inma
Rubenstein, J. L. R.
Martin, Gail R.
author Martínez, Salvador
author_facet Martínez, Salvador
Crossley, P. H.
Cobos, Inma
Rubenstein, J. L. R.
Martin, Gail R.
author_role author
author2 Crossley, P. H.
Cobos, Inma
Rubenstein, J. L. R.
Martin, Gail R.
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Fundación Séneca
Gobierno de la Región de Murcia
Human Frontier Science Program
National Institutes of Health (US)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Brain patterning
Cerebellum
Fgf8
Isthmic organizer
Midbrain
Neuromere boundaries
topic Brain patterning
Cerebellum
Fgf8
Isthmic organizer
Midbrain
Neuromere boundaries
description Beads containing recombinant FGF8 (FGF8-beads) were implanted in the prospective caudal diencephalon or midbrain of chick embryos at stages 9-12. This induced the neuroepithelium rostral and caudal to the FGF8-bead to form two ectopic, mirror-image midbrains. Furthermore, cells in direct contact with the bead formed an outgrowth that protruded laterally from the neural tube. Tissue within such lateral outgrowths developed proximally into isthmic nuclei and distally into a cerebellum-like structure. These morphogenetic effects were apparently due to FGF8-mediated changes in gene expression in the vicinity of the bead, including a repressive effect on Otx2 and an inductive effect on En1, Fgf8 and Wnt1 expression. The ectopic Fgf8 and Wnt1 expression domains formed nearly complete concentric rings around the FGF8-bead, with the Wnt1 ring outermost. These observations suggest that FGF8 induces the formation of a ring-like ectopic signaling center (organizer) in the lateral wall of the brain, similar to the one that normally encircles the neural tube at the isthmic constriction, which is located at the boundary between the prospective midbrain and hindbrain. This ectopic isthmic organizer apparently sends long-range patterning signals both rostrally and caudally, resulting in the development of the two ectopic midbrains. Interestingly, our data suggest that these inductive signals spread readily in a caudal direction, but are inhibited from spreading rostrally across diencephalic neuromere boundaries. These results provide insights into the mechanism by which FGF8 induces an ectopic organizer and suggest that a negative feedback loop between Fgf8 and Otx2 plays a key role in patterning the midbrain and anterior hindbrain.
publishDate 1999
dc.date.none.fl_str_mv 1999
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/307893
url http://hdl.handle.net/10261/307893
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Development
https://doi.org/10.1242/dev.126.6.1189
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Company of Biologists
publisher.none.fl_str_mv Company of Biologists
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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