Journal article
SFRP1 and SFRP2 dose-dependently regulate midbrain dopamine neuron development in vivo and in embryonic stem cells
J Kele, ER Andersson, JC Villaescusa, L Cajanek, CL Parish, S Bonilla, EM Toledo, V Bryja, JS Rubin, A Shimono, E Arenas
Stem Cells | WILEY-BLACKWELL | Published : 2012
DOI: 10.1002/stem.1049
Abstract
Secreted Frizzled related proteins (sFRPs) are a family of proteins that modulate Wnt signaling, which in turn regulates multiple aspects of ventral midbrain (VM) and dopamine (DA) neuron development. However, it is not known which Wnt signaling branch and what aspects of midbrain DA neuron development are regulated by sFRPs. Here, we show that sFRP1 and sFRP2 activate the Wnt/planar-cell-polarity/Rac1 pathway in DA cells. In the developing VM, sFRP1 and sFRP2 are expressed at low levels, and sFRP1-/- or sFRP2-/- mice had no detectable phenotype. However, compound sFRP1-/-;sFRP2-/- mutants revealed a Wnt/PCP phenotype similar to that previously described for Wnt5a-/- mice. This included an a..
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Awarded by European Commission
Funding Acknowledgements
We thank Carmen Ramirez-Castillejo, Helena Mira, and Carmen Salto, for support and assistance; Alessandra Nanni for secretarial help; Johan Glad for help with statistical analysis; Johnny Soderlund and Lottie Jansson-Sjostrand for additional assistance. This work was supported by grants from the Swedish Research Council (DBRM, VR2008:2811 and 3287), European Union (Neurostemcell and Eurostemcell), Swedish Foundation for Strategic Research (INGVAR and DBRM), Norwegian Research Council, and Karolinska Institute, National Health and Medical Research Council (NHMRC), Australia. J.K. was supported by the Swedish National Neuroscience Network. J.C.V. was supported by a FEBS Long-Term Fellowship. V. B. was supported by EMBO Installation Grant and Ministry of Education, Youth and Sports of the Czech Republic (MSM0021622430). C.L.P was supported by an NHMRC Career development Fellowship, Australia. J.K. is currently affiliated with Ludwig Institute for Cancer Research Ltd., Stockholm, Sweden; E.R.A. is currently affiliated with Department of Cellular and Molecular Biology, Karolinska Institute, Stockholm, Sweden; S.B. is currently affiliated with Instituto de Biomedicina de Sevilla, Hospital Virgen del Rocio, Sevilla, Spain; V.B. is currently affiliated with Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic, and Institute of Biophysics, Brno, Czech Republic.