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Publication : Wnt2 regulates progenitor proliferation in the developing ventral midbrain.

First Author  Sousa KM Year  2010
Journal  J Biol Chem Volume  285
Issue  10 Pages  7246-53
PubMed ID  20018874 Mgi Jnum  J:161745
Mgi Id  MGI:4461115 Doi  10.1074/jbc.M109.079822
Citation  Sousa KM, et al. (2010) Wnt2 regulates progenitor proliferation in the developing ventral midbrain. J Biol Chem 285(10):7246-53
abstractText  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.
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