Wnt2 regulates progenitor proliferation in the developing ventral midbrain
| Autor: | Richard A. Lang, Lukas Cajanek, Vitezslav Bryja, Ernest Arenas, Jennifer K. Ondr, Carina Palmberg, Gonçalo Castelo-Branco, J. Carlos Villaescusa, Brandon J. Wainwright, Kyle M. Sousa, Tomas Bergman, Wytske Hofstra |
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| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Cellular differentiation Dopamine Neurogenesis Biology Biochemistry Wnt2 Protein Midbrain 03 medical and health sciences Mice 0302 clinical medicine Mesencephalon Pregnancy Dopaminergic Cell Internal medicine medicine Animals Progenitor cell Molecular Biology Cells Cultured beta Catenin 030304 developmental biology Progenitor Cell Proliferation Mice Knockout Neurons 0303 health sciences Stem Cells Dopaminergic Cell Differentiation Cell Biology Cell biology Endocrinology nervous system Female Protein Processing Post-Translational 030217 neurology & neurosurgery medicine.drug Developmental Biology |
| Zdroj: | The Journal of biological chemistry. 285(10) |
| ISSN: | 1083-351X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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