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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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) |
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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 |
work_keys_str_mv |
AT diogoribeiro dkk1regulatesventralmidbraindopaminergicdifferentiationandmorphogenesis AT kristinaellwanger dkk1regulatesventralmidbraindopaminergicdifferentiationandmorphogenesis AT desireeglagow dkk1regulatesventralmidbraindopaminergicdifferentiationandmorphogenesis AT spyridontheofilopoulos dkk1regulatesventralmidbraindopaminergicdifferentiationandmorphogenesis AT ninascorsini dkk1regulatesventralmidbraindopaminergicdifferentiationandmorphogenesis AT anamartinvillalba dkk1regulatesventralmidbraindopaminergicdifferentiationandmorphogenesis AT christofniehrs dkk1regulatesventralmidbraindopaminergicdifferentiationandmorphogenesis AT ernestarenas dkk1regulatesventralmidbraindopaminergicdifferentiationandmorphogenesis |
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1718424111714140160 |