Dkk1 regulates ventral midbrain dopaminergic differentiation and morphogenesis.

Dickkopf1 (Dkk1) is a Wnt/β-catenin inhibitor that participates in many processes during embryonic development. One of its roles during embryogenesis is to induce head formation, since Dkk1-null mice lack head structures anterior to midbrain. The Wnt/β-catenin pathway is also known to regulate diffe...

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Autores principales: Diogo Ribeiro, Kristina Ellwanger, Désirée Glagow, Spyridon Theofilopoulos, Nina S Corsini, Ana Martin-Villalba, Christof Niehrs, Ernest Arenas
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Publicado: Public Library of Science (PLoS) 2011
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Acceso en línea:https://doaj.org/article/785d671a481e489f97a8a2fdd6913b71
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spelling oai:doaj.org-article:785d671a481e489f97a8a2fdd6913b712021-11-18T06:58:55ZDkk1 regulates ventral midbrain dopaminergic differentiation and morphogenesis.1932-620310.1371/journal.pone.0015786https://doaj.org/article/785d671a481e489f97a8a2fdd6913b712011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21347250/?tool=EBIhttps://doaj.org/toc/1932-6203Dickkopf1 (Dkk1) is a Wnt/β-catenin inhibitor that participates in many processes during embryonic development. One of its roles during embryogenesis is to induce head formation, since Dkk1-null mice lack head structures anterior to midbrain. The Wnt/β-catenin pathway is also known to regulate different aspects of ventral midbrain (VM) dopaminergic (DA) neuron development and, in vitro, Dkk1-mediated inhibition of the Wnt/β-catenin pathway improves the DA differentiation in mouse embryonic stem cells (mESC). However, the in vivo function of Dkk1 on the development of midbrain DA neurons remains to be elucidated. Here we examined Dkk1(+/-) embryos and found that Dkk1 is required for the differentiation of DA precursors/neuroblasts into DA neurons at E13.5. This deficit persisted until E17.5, when a defect in the number and distribution of VM DA neurons was detected. Furthermore, analysis of the few Dkk1(-/-) embryos that survived until E17.5 revealed a more severe loss of midbrain DA neurons and morphogenesis defects. Our results thus show that Dkk1 is required for midbrain DA differentiation and morphogenesis.Diogo RibeiroKristina EllwangerDésirée GlagowSpyridon TheofilopoulosNina S CorsiniAna Martin-VillalbaChristof NiehrsErnest ArenasPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 2, p e15786 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Diogo Ribeiro
Kristina Ellwanger
Désirée Glagow
Spyridon Theofilopoulos
Nina S Corsini
Ana Martin-Villalba
Christof Niehrs
Ernest Arenas
Dkk1 regulates ventral midbrain dopaminergic differentiation and morphogenesis.
description Dickkopf1 (Dkk1) is a Wnt/β-catenin inhibitor that participates in many processes during embryonic development. One of its roles during embryogenesis is to induce head formation, since Dkk1-null mice lack head structures anterior to midbrain. The Wnt/β-catenin pathway is also known to regulate different aspects of ventral midbrain (VM) dopaminergic (DA) neuron development and, in vitro, Dkk1-mediated inhibition of the Wnt/β-catenin pathway improves the DA differentiation in mouse embryonic stem cells (mESC). However, the in vivo function of Dkk1 on the development of midbrain DA neurons remains to be elucidated. Here we examined Dkk1(+/-) embryos and found that Dkk1 is required for the differentiation of DA precursors/neuroblasts into DA neurons at E13.5. This deficit persisted until E17.5, when a defect in the number and distribution of VM DA neurons was detected. Furthermore, analysis of the few Dkk1(-/-) embryos that survived until E17.5 revealed a more severe loss of midbrain DA neurons and morphogenesis defects. Our results thus show that Dkk1 is required for midbrain DA differentiation and morphogenesis.
format article
author Diogo Ribeiro
Kristina Ellwanger
Désirée Glagow
Spyridon Theofilopoulos
Nina S Corsini
Ana Martin-Villalba
Christof Niehrs
Ernest Arenas
author_facet Diogo Ribeiro
Kristina Ellwanger
Désirée Glagow
Spyridon Theofilopoulos
Nina S Corsini
Ana Martin-Villalba
Christof Niehrs
Ernest Arenas
author_sort Diogo Ribeiro
title Dkk1 regulates ventral midbrain dopaminergic differentiation and morphogenesis.
title_short Dkk1 regulates ventral midbrain dopaminergic differentiation and morphogenesis.
title_full Dkk1 regulates ventral midbrain dopaminergic differentiation and morphogenesis.
title_fullStr Dkk1 regulates ventral midbrain dopaminergic differentiation and morphogenesis.
title_full_unstemmed Dkk1 regulates ventral midbrain dopaminergic differentiation and morphogenesis.
title_sort dkk1 regulates ventral midbrain dopaminergic differentiation and morphogenesis.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/785d671a481e489f97a8a2fdd6913b71
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