Wnt2 regulates progenitor proliferation in the developing ventral midbrain

Sousa, Kyle M., Villaescusa, J. Carlos, Cajanek, Lukas, Ondr, Jennifer K., Castelo-Branco, Goncalo, Hofstra, Wytske, Bryja, Vitezslav, Palmberg, Carina, Bergman, Tomas, Wainwright, Brandon, Lang, Richard A. and Arenas, Ernest (2010) Wnt2 regulates progenitor proliferation in the developing ventral midbrain. Journal of Biological Chemistry, 285 10: 7246-7253. doi:10.1074/jbc.M109.079822

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Author Sousa, Kyle M.
Villaescusa, J. Carlos
Cajanek, Lukas
Ondr, Jennifer K.
Castelo-Branco, Goncalo
Hofstra, Wytske
Bryja, Vitezslav
Palmberg, Carina
Bergman, Tomas
Wainwright, Brandon
Lang, Richard A.
Arenas, Ernest
Title Wnt2 regulates progenitor proliferation in the developing ventral midbrain
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2010-03
Sub-type Article (original research)
DOI 10.1074/jbc.M109.079822
Open Access Status File (Publisher version)
Volume 285
Issue 10
Start page 7246
End page 7253
Total pages 8
Place of publication Bethesda, MD, U. S. A.
Publisher American Society for Biochemistry and Molecular Biology
Collection year 2011
Language eng
Subject C1
970106 Expanding Knowledge in the Biological Sciences
060403 Developmental Genetics (incl. Sex Determination)
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 β-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.
Keyword Cell Cycle
Development Differentiation
Stem Cell
Signal Transduction
Stem Cells
Wnt pathway
Parkinson Disease
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 32 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 04 Mar 2010, 09:19:57 EST by Susan Allen on behalf of Institute for Molecular Bioscience