Journal article

Wnt/beta-Catenin Signaling Blockade Promotes Neuronal Induction and Dopaminergic Differentiation in Embryonic Stem Cells

Lukas Cajanek, Diogo Ribeiro, Isabel Liste, Clare L Parish, Vitezslav Bryja, Ernest Arenas

Stem Cells | WILEY | Published : 2009

Abstract

Embryonic stem cells (ESCs) represent not only a promising source of cells for cell replacement therapy, but also a tool to study the molecular mechanisms underlying cellular signaling and dopaminergic (DA) neuron development. One of the main regulators of DA neuron development is Wnt signaling. Here we used mouse ESCs (mESCs) lacking Wnt1 or the low-density lipoprotein receptor-related protein 6 (LRP6) to decipher the action of Wnt/beta-catenin signaling on DA neuron development in mESCs. We provide evidence that the absence of LRP6 abrogates responsiveness of mESCs to Wnt ligand stimulation. Using two differentiation protocols, we show that the loss of Wnt1 or LRP6 increases neuroectoderma..

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Grants

Awarded by Swedish Research Council


Awarded by Ministry of Education, Youth, and Sports of the Czech Republic


Awarded by Academy of Sciences of the Czech Republic


Awarded by Czech Science Foundation


Awarded by KID


Awarded by Portuguese Government


Funding Acknowledgements

We thank Dr. R. T. Moon (University of Washington, Seattle, WA) for SuperTOP-FLASH/ SuperFOP-FLASH plasmids, Dr. G. Minchiotti (Institute of Genetics and Biophysics, Naples, Italy) for providing R1 mESC. We would like to thank Johny Soderlund and Lottie Jansson-Sjostrand for technical assistance and the members of Arenas lab for stimulating discussions. This work was supported by grants from the European Union (Neurostemcell), Swedish Foundation for Strategic Research (INGVAR and CEDB projects), Swedish Research Council (VR2008:2811 and DBRM), Norwegian Research Council and Karolinska Institute to EA, as well as grants from the Ministry of Education, Youth, and Sports of the Czech Republic (MSM0021622430), Academy of Sciences of the Czech Republic (AVOZ50040507, AVOZ50040702), EMBO Installation Grant and Czech Science Foundation (204/09/0498) to VB. LC was supported by a KID grant (6110/06-225) from Karolinska Institute. DR was supported by the Foundation for Science and Technology from the Portuguese Government (SFRH/BD/24585/2005), CLP was supported by a Human Frontiers Science Program long-term fellowship and National Health and Medical Research Council, Australia, CJ Martin fellowship.