Dampening the signals transduced through hedgehog via microRNA miR-7 facilitates Notch-induced tumourigenesis

Autores
Da Ros, Vanina Gabriela; Gutierrez-Perez, Irene; Ferres-Marco, Dolors; Dominguez, María
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fine-tuned Notch and Hedgehog signaling pathways via attenuators and dampers have long been recognized as important
mechanisms to ensure the proper size and differentiation of many organs and tissues. This notion is further supported by
identification of mutations in these pathways in human cancer cells. However, although it is common that the Notch and
Hedgehog pathways influence growth and patterning within the same organ through the establishment of organizing
regions, the cross-talk between these two pathways and how the distinct organizing activities are integrated during growth
is poorly understood. Here, in an unbiased genetic screen in the Drosophila melanogaster eye, we found that tumour-like
growth was provoked by cooperation between the microRNA miR-7 and the Notch pathway. Surprisingly, the molecular
basis of this cooperation between miR-7 and Notch converged on the silencing of Hedgehog signalling. In mechanistic
terms, miR-7 silenced the interference hedgehog (ihog) Hedgehog receptor, while Notch repressed expression of the brother
of ihog (boi) Hedgehog receptor. Tumourigenesis was induced co-operatively following Notch activation and reduced
Hedgehog signalling, either via overexpression of the microRNA or through specific down-regulation of ihog, hedgehog,
smoothened, or cubitus interruptus or via overexpression of the cubitus interruptus repressor form. Conversely, increasing
Hedgehog signalling prevented eye overgrowth induced by the microRNA and Notch pathway. Further, we show that
blocking Hh signal transduction in clones of cells mutant for smoothened also enhance the organizing activity and growth
by Delta-Notch signalling in the wing primordium. Together, these findings uncover a hitherto unsuspected tumour
suppressor role for the Hedgehog signalling and reveal an unanticipated cooperative antagonism between two pathways
extensively used in growth control and cancer.
Fil: Da Ros,Vanina Gabriela . CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS. INST.DE NEUROCIENCIA DE ALICANTE.
Fil: Gutierrez-Perez, Irene. CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS. INST.DE NEUROCIENCIA DE ALICANTE.
Fil: Ferres-Marco, Dolors. CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS. INST.DE NEUROCIENCIA DE ALICANTE.
Fil: Dominguez M. CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS. INST.DE NEUROCIENCIA DE ALICANTE.
Materia
Drosophila
microRNA
Notch
Hedgehog
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/489
Acceder
id CONICETDig_e34374140e0d38d703c92e05657b1941
oai_identifier_str oai:ri.conicet.gov.ar:11336/489
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Dampening the signals transduced through hedgehog via microRNA miR-7 facilitates Notch-induced tumourigenesisDa Ros, Vanina GabrielaGutierrez-Perez, IreneFerres-Marco, DolorsDominguez, MaríaDrosophilamicroRNANotchHedgehoghttps://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6Fine-tuned Notch and Hedgehog signaling pathways via attenuators and dampers have long been recognized as important<br />mechanisms to ensure the proper size and differentiation of many organs and tissues. This notion is further supported by<br />identification of mutations in these pathways in human cancer cells. However, although it is common that the Notch and<br />Hedgehog pathways influence growth and patterning within the same organ through the establishment of organizing<br />regions, the cross-talk between these two pathways and how the distinct organizing activities are integrated during growth<br />is poorly understood. Here, in an unbiased genetic screen in the Drosophila melanogaster eye, we found that tumour-like<br />growth was provoked by cooperation between the microRNA miR-7 and the Notch pathway. Surprisingly, the molecular<br />basis of this cooperation between miR-7 and Notch converged on the silencing of Hedgehog signalling. In mechanistic<br />terms, miR-7 silenced the interference hedgehog (ihog) Hedgehog receptor, while Notch repressed expression of the brother<br />of ihog (boi) Hedgehog receptor. Tumourigenesis was induced co-operatively following Notch activation and reduced<br />Hedgehog signalling, either via overexpression of the microRNA or through specific down-regulation of ihog, hedgehog,<br />smoothened, or cubitus interruptus or via overexpression of the cubitus interruptus repressor form. Conversely, increasing<br />Hedgehog signalling prevented eye overgrowth induced by the microRNA and Notch pathway. Further, we show that<br />blocking Hh signal transduction in clones of cells mutant for smoothened also enhance the organizing activity and growth<br />by Delta-Notch signalling in the wing primordium. Together, these findings uncover a hitherto unsuspected tumour<br />suppressor role for the Hedgehog signalling and reveal an unanticipated cooperative antagonism between two pathways<br />extensively used in growth control and cancer.Fil: Da Ros,Vanina Gabriela . CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS. INST.DE NEUROCIENCIA DE ALICANTE.Fil: Gutierrez-Perez, Irene. CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS. INST.DE NEUROCIENCIA DE ALICANTE.Fil: Ferres-Marco, Dolors. CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS. INST.DE NEUROCIENCIA DE ALICANTE.Fil: Dominguez M. CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS. INST.DE NEUROCIENCIA DE ALICANTE.Public Library Science2013-05-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/489Da Ros, Vanina Gabriela; Gutierrez-Perez, Irene; Ferres-Marco, Dolors; Dominguez, María; Dampening the signals transduced through hedgehog via microRNA miR-7 facilitates Notch-induced tumourigenesis; Public Library Science; Plos Biology; 11; 2013-5; 1001554-1001554;1544-9173enginfo:eu-repo/semantics/altIdentifier/url/doi:10.1371/journal.pbio.1001554info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:44:30Zoai:ri.conicet.gov.ar:11336/489instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:44:30.433CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Dampening the signals transduced through hedgehog via microRNA miR-7 facilitates Notch-induced tumourigenesis
title Dampening the signals transduced through hedgehog via microRNA miR-7 facilitates Notch-induced tumourigenesis
spellingShingle Dampening the signals transduced through hedgehog via microRNA miR-7 facilitates Notch-induced tumourigenesis
Da Ros, Vanina Gabriela
Drosophila
microRNA
Notch
Hedgehog
title_short Dampening the signals transduced through hedgehog via microRNA miR-7 facilitates Notch-induced tumourigenesis
title_full Dampening the signals transduced through hedgehog via microRNA miR-7 facilitates Notch-induced tumourigenesis
title_fullStr Dampening the signals transduced through hedgehog via microRNA miR-7 facilitates Notch-induced tumourigenesis
title_full_unstemmed Dampening the signals transduced through hedgehog via microRNA miR-7 facilitates Notch-induced tumourigenesis
title_sort Dampening the signals transduced through hedgehog via microRNA miR-7 facilitates Notch-induced tumourigenesis
dc.creator.none.fl_str_mv Da Ros, Vanina Gabriela
Gutierrez-Perez, Irene
Ferres-Marco, Dolors
Dominguez, María
author Da Ros, Vanina Gabriela
author_facet Da Ros, Vanina Gabriela
Gutierrez-Perez, Irene
Ferres-Marco, Dolors
Dominguez, María
author_role author
author2 Gutierrez-Perez, Irene
Ferres-Marco, Dolors
Dominguez, María
author2_role author
author
author
dc.subject.none.fl_str_mv Drosophila
microRNA
Notch
Hedgehog
topic Drosophila
microRNA
Notch
Hedgehog
purl_subject.fl_str_mv https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
dc.description.none.fl_txt_mv Fine-tuned Notch and Hedgehog signaling pathways via attenuators and dampers have long been recognized as important<br />mechanisms to ensure the proper size and differentiation of many organs and tissues. This notion is further supported by<br />identification of mutations in these pathways in human cancer cells. However, although it is common that the Notch and<br />Hedgehog pathways influence growth and patterning within the same organ through the establishment of organizing<br />regions, the cross-talk between these two pathways and how the distinct organizing activities are integrated during growth<br />is poorly understood. Here, in an unbiased genetic screen in the Drosophila melanogaster eye, we found that tumour-like<br />growth was provoked by cooperation between the microRNA miR-7 and the Notch pathway. Surprisingly, the molecular<br />basis of this cooperation between miR-7 and Notch converged on the silencing of Hedgehog signalling. In mechanistic<br />terms, miR-7 silenced the interference hedgehog (ihog) Hedgehog receptor, while Notch repressed expression of the brother<br />of ihog (boi) Hedgehog receptor. Tumourigenesis was induced co-operatively following Notch activation and reduced<br />Hedgehog signalling, either via overexpression of the microRNA or through specific down-regulation of ihog, hedgehog,<br />smoothened, or cubitus interruptus or via overexpression of the cubitus interruptus repressor form. Conversely, increasing<br />Hedgehog signalling prevented eye overgrowth induced by the microRNA and Notch pathway. Further, we show that<br />blocking Hh signal transduction in clones of cells mutant for smoothened also enhance the organizing activity and growth<br />by Delta-Notch signalling in the wing primordium. Together, these findings uncover a hitherto unsuspected tumour<br />suppressor role for the Hedgehog signalling and reveal an unanticipated cooperative antagonism between two pathways<br />extensively used in growth control and cancer.
Fil: Da Ros,Vanina Gabriela . CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS. INST.DE NEUROCIENCIA DE ALICANTE.
Fil: Gutierrez-Perez, Irene. CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS. INST.DE NEUROCIENCIA DE ALICANTE.
Fil: Ferres-Marco, Dolors. CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS. INST.DE NEUROCIENCIA DE ALICANTE.
Fil: Dominguez M. CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS. INST.DE NEUROCIENCIA DE ALICANTE.
description Fine-tuned Notch and Hedgehog signaling pathways via attenuators and dampers have long been recognized as important<br />mechanisms to ensure the proper size and differentiation of many organs and tissues. This notion is further supported by<br />identification of mutations in these pathways in human cancer cells. However, although it is common that the Notch and<br />Hedgehog pathways influence growth and patterning within the same organ through the establishment of organizing<br />regions, the cross-talk between these two pathways and how the distinct organizing activities are integrated during growth<br />is poorly understood. Here, in an unbiased genetic screen in the Drosophila melanogaster eye, we found that tumour-like<br />growth was provoked by cooperation between the microRNA miR-7 and the Notch pathway. Surprisingly, the molecular<br />basis of this cooperation between miR-7 and Notch converged on the silencing of Hedgehog signalling. In mechanistic<br />terms, miR-7 silenced the interference hedgehog (ihog) Hedgehog receptor, while Notch repressed expression of the brother<br />of ihog (boi) Hedgehog receptor. Tumourigenesis was induced co-operatively following Notch activation and reduced<br />Hedgehog signalling, either via overexpression of the microRNA or through specific down-regulation of ihog, hedgehog,<br />smoothened, or cubitus interruptus or via overexpression of the cubitus interruptus repressor form. Conversely, increasing<br />Hedgehog signalling prevented eye overgrowth induced by the microRNA and Notch pathway. Further, we show that<br />blocking Hh signal transduction in clones of cells mutant for smoothened also enhance the organizing activity and growth<br />by Delta-Notch signalling in the wing primordium. Together, these findings uncover a hitherto unsuspected tumour<br />suppressor role for the Hedgehog signalling and reveal an unanticipated cooperative antagonism between two pathways<br />extensively used in growth control and cancer.
publishDate 2013
dc.date.none.fl_str_mv 2013-05-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/489
Da Ros, Vanina Gabriela; Gutierrez-Perez, Irene; Ferres-Marco, Dolors; Dominguez, María; Dampening the signals transduced through hedgehog via microRNA miR-7 facilitates Notch-induced tumourigenesis; Public Library Science; Plos Biology; 11; 2013-5; 1001554-1001554;
1544-9173
url http://hdl.handle.net/11336/489
identifier_str_mv Da Ros, Vanina Gabriela; Gutierrez-Perez, Irene; Ferres-Marco, Dolors; Dominguez, María; Dampening the signals transduced through hedgehog via microRNA miR-7 facilitates Notch-induced tumourigenesis; Public Library Science; Plos Biology; 11; 2013-5; 1001554-1001554;
1544-9173
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/doi:10.1371/journal.pbio.1001554
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library Science
publisher.none.fl_str_mv Public Library Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844614482892947456
score 13.070432

Publicaciones similares