DOI: 10.1073/pnas.1534900100. Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a

Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a

10.1073/pnas.1534900100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The Wnts are a family of glycoproteins that regulate cell proliferation, fate decisions, and differentiation. In our study, we examined the contribution of Wnts to the development of ventral midbrain (VM) dopaminergic (DA) neurons. Our results show that β-catenin is expressed in DA precursor cells and that β-catenin signaling takes place in these cells, as assessed in TOPGAL [Tcf optimal-promoter β-galactosidase] reporter mice. We also found that Wnt-1, -3a, and -5a expression is differentially regulated during development and that partially purified Wnts distinctively regulate VM development. Wnt-3a promoted the proliferation of precursor cells expressing the orphan nuclear receptor-related factor 1 (Nurr1) but did not increase the number of tyrosine hydroxylase-positive neurons. Instead, Wnt-1 and -5a increased the number of rat midbrain DA neurons in rat embryonic day 14.5 precursor cultures by two distinct mechanisms. Wnt-1 predominantly increased the proliferation of Nurr1+ precursors, up-regulated cyclins D1 and D3, and down-regulated p27 and p57 mRNAs. In contrast, Wnt-5a primarily increased the proportion of Nurr1+ precursors that acquired a neuronal DA phenotype and up-regulated the expression of Ptx3 and c-ret mRNA. Moreover, the soluble cysteine-rich domain of Frizzled-8 (a Wnt inhibitor) blocked endogenous Wnts and the effects of Wnt-1 and -5a on proliferation and the acquisition of a DA phenotype in precursor cultures. These findings indicate that Wnts are key regulators of proliferation and differentiation of DA precursors during VM neurogenesis and that different Wnts have specific and unique activity profiles.

Bibliography

Castelo-Branco, G., Wagner, J., Rodriguez, F. J., Kele, J., Sousa, K., Rawal, N., Pasolli, H. A., Fuchs, E., Kitajewski, J., & Arenas, E. (2003). Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a. Proceedings of the National Academy of Sciences, 100(22), 12747â12752.

Authors 10

Gonçalo Castelo-Branco (first)
Joseph Wagner (additional)
Francisco J. Rodriguez (additional)
Julianna Kele (additional)
Kyle Sousa (additional)
Nina Rawal (additional)
Hilda Amalia Pasolli (additional)
Elaine Fuchs (additional)
Jan Kitajewski (additional)
Ernest Arenas (additional)

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Dates

Type	When
Created	21 years, 9 months ago (Oct. 29, 2003, 1:26 a.m.)
Deposited	3 years, 3 months ago (April 25, 2022, 9:39 p.m.)
Indexed	4 days, 20 hours ago (Aug. 20, 2025, 8:58 a.m.)
Issued	21 years, 10 months ago (Oct. 13, 2003)
Published	21 years, 10 months ago (Oct. 13, 2003)
Published Online	21 years, 10 months ago (Oct. 13, 2003)
Published Print	21 years, 9 months ago (Oct. 28, 2003)

Funders 0

None

BibTeX

@article{Castelo_Branco_2003, title={Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a}, volume={100}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1534900100}, DOI={10.1073/pnas.1534900100}, number={22}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Castelo-Branco, Gonçalo and Wagner, Joseph and Rodriguez, Francisco J. and Kele, Julianna and Sousa, Kyle and Rawal, Nina and Pasolli, Hilda Amalia and Fuchs, Elaine and Kitajewski, Jan and Arenas, Ernest}, year={2003}, month=oct, pages={12747–12752} }

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