The isthmic organizer signal FGF8 is required for cell survival in the prospective midbrain and cerebellum

Numerous studies have demonstrated that the midbrain and cerebellum develop from a region of the early neural tube comprising two distinct territories known as the mesencephalon (mes) and rostral metencephalon (met; rhombomere 1), respectively. Development of the mes and met is thought to be regulat...

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Autores: Chi, Candace L., Martínez, Salvador, Wurst, Wolfgang, Martin, Gail R.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2003
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/338469
Acceso en línea:http://hdl.handle.net/10261/338469
Access Level:acceso abierto
Palabra clave:Brain patterning
Cerebellum
Fgf8
Isthmic organizer
Mesencephalon
Metencephalon
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spelling The isthmic organizer signal FGF8 is required for cell survival in the prospective midbrain and cerebellumChi, Candace L.Martínez, SalvadorWurst, WolfgangMartin, Gail R.Brain patterningCerebellumFgf8Isthmic organizerMesencephalonMetencephalonNumerous studies have demonstrated that the midbrain and cerebellum develop from a region of the early neural tube comprising two distinct territories known as the mesencephalon (mes) and rostral metencephalon (met; rhombomere 1), respectively. Development of the mes and met is thought to be regulated by molecules produced by a signaling center, termed the isthmic organizer (IsO), which is localized at the boundary between them. FGF8 and WNT1 have been implicated as key components of IsO signaling activity, and previous studies have shown that in Wnt1(-/-) embryos, the mes/met is deleted by the 30 somite stage ( approximately E10) (McMahon, A. P. and Bradley, A. (1990) Cell 62, 1073-1085). We have studied the function of FGF8 in mouse mes/met development using a conditional gene inactivation approach. In our mutant embryos, Fgf8 expression was transiently detected, but then was eliminated in the mes/met by the 10 somite stage ( approximately E8.75). This resulted in a failure to maintain expression of Wnt1 as well as Fgf17, Fgf18, and Gbx2 in the mes/met at early somite stages, and in the absence of the midbrain and cerebellum at E17.5. We show that a major cause of the deletion of these structures is ectopic cell death in the mes/met between the 7 and 30 somite stages. Interestingly, we found that the prospective midbrain was deleted at an earlier stage than the prospective cerebellum. We observed a remarkably similar pattern of cell death in Wnt1 null homozygotes, and also detected ectopic mes/met cell death in En1 null homozygotes. Our data show that Fgf8 is part of a complex gene regulatory network that is essential for cell survival in the mes/met.C.L.C. was the recipient of a predoctoral fellowship from the National Science Foundation and was supported by NIH Training grant T32 HD07470. This work was supported by DFG grant SFB 190 (to W.W.), by European Union grants QLRT-1999-31556, 1999-31625,2000-02310 and grant DGI BFI2002-02979 (to S.M.), and by NIH grant RO1 HD25331(to G.R.M.).Peer reviewedCompany of BiologistsNational Science Foundation (US)National Institutes of Health (US)German Research FoundationEuropean CommissionDirección General de Investigación Científica y Técnica, DGICT (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320232003info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/338469reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1242/dev.00487Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3384692026-05-22T06:33:51Z
dc.title.none.fl_str_mv The isthmic organizer signal FGF8 is required for cell survival in the prospective midbrain and cerebellum
title The isthmic organizer signal FGF8 is required for cell survival in the prospective midbrain and cerebellum
spellingShingle The isthmic organizer signal FGF8 is required for cell survival in the prospective midbrain and cerebellum
Chi, Candace L.
Brain patterning
Cerebellum
Fgf8
Isthmic organizer
Mesencephalon
Metencephalon
title_short The isthmic organizer signal FGF8 is required for cell survival in the prospective midbrain and cerebellum
title_full The isthmic organizer signal FGF8 is required for cell survival in the prospective midbrain and cerebellum
title_fullStr The isthmic organizer signal FGF8 is required for cell survival in the prospective midbrain and cerebellum
title_full_unstemmed The isthmic organizer signal FGF8 is required for cell survival in the prospective midbrain and cerebellum
title_sort The isthmic organizer signal FGF8 is required for cell survival in the prospective midbrain and cerebellum
dc.creator.none.fl_str_mv Chi, Candace L.
Martínez, Salvador
Wurst, Wolfgang
Martin, Gail R.
author Chi, Candace L.
author_facet Chi, Candace L.
Martínez, Salvador
Wurst, Wolfgang
Martin, Gail R.
author_role author
author2 Martínez, Salvador
Wurst, Wolfgang
Martin, Gail R.
author2_role author
author
author
dc.contributor.none.fl_str_mv National Science Foundation (US)
National Institutes of Health (US)
German Research Foundation
European Commission
Dirección General de Investigación Científica y Técnica, DGICT (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Brain patterning
Cerebellum
Fgf8
Isthmic organizer
Mesencephalon
Metencephalon
topic Brain patterning
Cerebellum
Fgf8
Isthmic organizer
Mesencephalon
Metencephalon
description Numerous studies have demonstrated that the midbrain and cerebellum develop from a region of the early neural tube comprising two distinct territories known as the mesencephalon (mes) and rostral metencephalon (met; rhombomere 1), respectively. Development of the mes and met is thought to be regulated by molecules produced by a signaling center, termed the isthmic organizer (IsO), which is localized at the boundary between them. FGF8 and WNT1 have been implicated as key components of IsO signaling activity, and previous studies have shown that in Wnt1(-/-) embryos, the mes/met is deleted by the 30 somite stage ( approximately E10) (McMahon, A. P. and Bradley, A. (1990) Cell 62, 1073-1085). We have studied the function of FGF8 in mouse mes/met development using a conditional gene inactivation approach. In our mutant embryos, Fgf8 expression was transiently detected, but then was eliminated in the mes/met by the 10 somite stage ( approximately E8.75). This resulted in a failure to maintain expression of Wnt1 as well as Fgf17, Fgf18, and Gbx2 in the mes/met at early somite stages, and in the absence of the midbrain and cerebellum at E17.5. We show that a major cause of the deletion of these structures is ectopic cell death in the mes/met between the 7 and 30 somite stages. Interestingly, we found that the prospective midbrain was deleted at an earlier stage than the prospective cerebellum. We observed a remarkably similar pattern of cell death in Wnt1 null homozygotes, and also detected ectopic mes/met cell death in En1 null homozygotes. Our data show that Fgf8 is part of a complex gene regulatory network that is essential for cell survival in the mes/met.
publishDate 2003
dc.date.none.fl_str_mv 2003
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/10261/338469
url http://hdl.handle.net/10261/338469
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1242/dev.00487
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 15.81155

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