title: Wnt2 regulates progenitor proliferation in the developing ventral midbrain.
abstract: Wnts are secreted, lipidated proteins that regulate multiple aspects of brain development, including dopaminergic neuron development. In this study, we perform the first purification and signaling analysis of Wnt2 and define the function of Wnt2 in ventral midbrain precursor cultures, as well as in Wnt2-null mice in vivo. We found that purified Wnt2 induces the phosphorylation of both Lrp5/6 and Dvl-2/3, and activates beta-catenin in SN4741 dopaminergic cells. Moreover, purified Wnt2 increases progenitor proliferation, and the number of dopaminergic neurons in ventral midbrain precursor cultures. In agreement with these findings, analysis of the ventral midbrain of developing Wnt2-null mice revealed a decrease in progenitor proliferation and neurogenesis that lead to a decrease in the number of postmitotic precursors and dopaminergic neurons. Collectively, our observations identify Wnt2 as a novel regulator of dopaminergic progenitors and dopaminergic neuron development.
authors.affiliation: Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Scheeles väg 1, A1:2, 17177 Stockholm, Sweden.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Sousa
authors.forename: J Carlos
authors.initials: JC
authors.lastname: Villaescusa
authors.forename: Lukas
authors.initials: L
authors.lastname: Cajanek
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Ondr
authors.forename: Goncalo
authors.initials: G
authors.lastname: Castelo-Branco
authors.forename: Wytske
authors.initials: W
authors.lastname: Hofstra
authors.forename: Vitezslav
authors.initials: V
authors.lastname: Bryja
authors.forename: Carina
authors.initials: C
authors.lastname: Palmberg
authors.forename: Tomas
authors.initials: T
authors.lastname: Bergman
authors.forename: Brandon
authors.initials: B
authors.lastname: Wainwright
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lang
authors.forename: Ernest
authors.initials: E
authors.lastname: Arenas
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism; D005260:Female; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D011247:Pregnancy; D011499:Protein Processing, Post-Translational; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D051154:Wnt2 Protein / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051154:Wnt2 Protein; D051176:beta Catenin; D004298:Dopamine