title: Dkk1 regulates ventral midbrain dopaminergic differentiation and morphogenesis.
abstract: 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.
authors.affiliation: Section of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
authors.forename: Diogo
authors.initials: D
authors.lastname: Ribeiro
authors.forename: Kristina
authors.initials: K
authors.lastname: Ellwanger
authors.forename: Désirée
authors.initials: D
authors.lastname: Glagow
authors.forename: Spyridon
authors.initials: S
authors.lastname: Theofilopoulos
authors.forename: Nina S
authors.initials: NS
authors.lastname: Corsini
authors.forename: Ana
authors.initials: A
authors.lastname: Martin-Villalba
authors.forename: Christof
authors.initials: C
authors.lastname: Niehrs
authors.forename: Ernest
authors.initials: E
authors.lastname: Arenas
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008636:Mesencephalon / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis; D009154:Mutation; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000378:metabolism
chemical_list: C501127:Dkk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2