The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye

Embryopathies that develop as a consequence of maternal diabetes have been studied intensely in both experimental and clinical scenarios. Accordingly, hyperglycaemia has been shown to downregulate the expression of elements in the non-canonical Wnt-PCP pathway, such as the Dishevelled-associated act...

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Autores: López-Escobar, Beatriz, Cano, David A., Rojas, Anabel, Felipe, Beatriz de, Palma, Francisco, Sánchez Alcázar, José Antonio, Henderson, Deborah, Ybot González, Patricia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/62290
Acceso en línea:http://hdl.handle.net/11441/62290
https://doi.org/10.1242/dmm.017723
Access Level:acceso abierto
Palabra clave:Diabetes
Wnt-PCP pathway
Daam1
Eye defects
Heart defects
Neural tube defects
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spelling The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eyeLópez-Escobar, BeatrizCano, David A.Rojas, AnabelFelipe, Beatriz dePalma, FranciscoSánchez Alcázar, José AntonioHenderson, DeborahYbot González, PatriciaDiabetesWnt-PCP pathwayDaam1Eye defectsHeart defectsNeural tube defectsEmbryopathies that develop as a consequence of maternal diabetes have been studied intensely in both experimental and clinical scenarios. Accordingly, hyperglycaemia has been shown to downregulate the expression of elements in the non-canonical Wnt-PCP pathway, such as the Dishevelled-associated activator of morphogenesis 1 (Daam1) and Vangl2. Daam1 is a formin that is essential for actin polymerization and for cytoskeletal reorganization, and it is expressed strongly in certain organs during mouse development, including the eye, neural tube and heart. Daam1gt/gt and Daam1gt/+ embryos develop ocular defects (anophthalmia or microphthalmia) that are similar to those detected as a result of hyperglycaemia. Indeed, studying the effects of maternal diabetes on the Wnt-PCP pathway demonstrated that there was strong association with the Daam1 genotype, whereby the embryopathy observed in Daam1gt/+ mutant embryos of diabetic dams was more severe. There was evidence that embryonic exposure to glucose in vitro diminishes the expression of genes in the Wnt-PCP pathway, leading to altered cytoskeletal organization, cell shape and cell polarity in the optic vesicle. Hence, the Wnt-PCP pathway appears to influence cell morphology and cell polarity, events that drive the cellular movements required for optic vesicle formation and that, in turn, are required to maintain the fate determination. Here, we demonstrate that the Wnt-PCP pathway is involved in the early stages of mouse eye development and that it is altered by diabetes, provoking the ocular phenotype observed in the affected embryos.Company of Biologists LimitedFisiología Médica y Biofísica2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/11441/62290https://doi.org/10.1242/dmm.017723reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésDMM Disease Models and Mechanisms, 8 (2), 157-168.info:eu-repo/semantics/openAccessoai:idus.us.es:11441/622902026-06-17T12:51:07Z
dc.title.none.fl_str_mv The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye
title The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye
spellingShingle The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye
López-Escobar, Beatriz
Diabetes
Wnt-PCP pathway
Daam1
Eye defects
Heart defects
Neural tube defects
title_short The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye
title_full The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye
title_fullStr The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye
title_full_unstemmed The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye
title_sort The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye
dc.creator.none.fl_str_mv López-Escobar, Beatriz
Cano, David A.
Rojas, Anabel
Felipe, Beatriz de
Palma, Francisco
Sánchez Alcázar, José Antonio
Henderson, Deborah
Ybot González, Patricia
author López-Escobar, Beatriz
author_facet López-Escobar, Beatriz
Cano, David A.
Rojas, Anabel
Felipe, Beatriz de
Palma, Francisco
Sánchez Alcázar, José Antonio
Henderson, Deborah
Ybot González, Patricia
author_role author
author2 Cano, David A.
Rojas, Anabel
Felipe, Beatriz de
Palma, Francisco
Sánchez Alcázar, José Antonio
Henderson, Deborah
Ybot González, Patricia
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Fisiología Médica y Biofísica
dc.subject.none.fl_str_mv Diabetes
Wnt-PCP pathway
Daam1
Eye defects
Heart defects
Neural tube defects
topic Diabetes
Wnt-PCP pathway
Daam1
Eye defects
Heart defects
Neural tube defects
description Embryopathies that develop as a consequence of maternal diabetes have been studied intensely in both experimental and clinical scenarios. Accordingly, hyperglycaemia has been shown to downregulate the expression of elements in the non-canonical Wnt-PCP pathway, such as the Dishevelled-associated activator of morphogenesis 1 (Daam1) and Vangl2. Daam1 is a formin that is essential for actin polymerization and for cytoskeletal reorganization, and it is expressed strongly in certain organs during mouse development, including the eye, neural tube and heart. Daam1gt/gt and Daam1gt/+ embryos develop ocular defects (anophthalmia or microphthalmia) that are similar to those detected as a result of hyperglycaemia. Indeed, studying the effects of maternal diabetes on the Wnt-PCP pathway demonstrated that there was strong association with the Daam1 genotype, whereby the embryopathy observed in Daam1gt/+ mutant embryos of diabetic dams was more severe. There was evidence that embryonic exposure to glucose in vitro diminishes the expression of genes in the Wnt-PCP pathway, leading to altered cytoskeletal organization, cell shape and cell polarity in the optic vesicle. Hence, the Wnt-PCP pathway appears to influence cell morphology and cell polarity, events that drive the cellular movements required for optic vesicle formation and that, in turn, are required to maintain the fate determination. Here, we demonstrate that the Wnt-PCP pathway is involved in the early stages of mouse eye development and that it is altered by diabetes, provoking the ocular phenotype observed in the affected embryos.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11441/62290
https://doi.org/10.1242/dmm.017723
url http://hdl.handle.net/11441/62290
https://doi.org/10.1242/dmm.017723
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv DMM Disease Models and Mechanisms, 8 (2), 157-168.
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Company of Biologists Limited
publisher.none.fl_str_mv Company of Biologists Limited
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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