Wnt2 Regulates Progenitor Proliferation in the Developing Ventral Midbrain

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Authors	SOUSA Kyle VILLAESCUSA Carlos ČAJÁNEK Lukáš ONDR Jennifer CASTELO-BRANCO Goncalo HOFSTRA Wytske BRYJA Vítězslav PALMBERG Carina BERGMAN Tomas WAINWRIGHT Brandon LANG Richard ARENAS Ernest
Year of publication	2010
Type	Article in Periodical
Magazine / Source	Journal of Biological Chemistry
MU Faculty or unit	Faculty of Science
Citation
Doi	http://dx.doi.org/10.1074/jbc.M109.079822
Field	Genetics and molecular biology
Keywords	Wnt2; dopaminergic neuron; ventral midbrain
Description	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.