Wnt2 regulates progenitor proliferation in the developing ventral midbrain.
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.
Sousa
Kyle M
KM
Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Scheeles väg 1, A1:2, 17177 Stockholm, Sweden.
Villaescusa
J Carlos
JC
Cajanek
Lukas
L
Ondr
Jennifer K
JK
Castelo-Branco
Goncalo
G
Hofstra
Wytske
W
Bryja
Vitezslav
V
Palmberg
Carina
C
Bergman
Tomas
T
Wainwright
Brandon
B
Lang
Richard A
RA
Arenas
Ernest
E
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
D051154:Wnt2 Protein; D051176:beta Catenin; D004298:Dopamine