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@article{1093433,
author = {Kele, Julianna and Andersson, Emma R. and Villaescusa Ramirez, Juan Carlos and Čajánek, Lukáš and Parish, Clare L. and Bonilla, Sonia and Toledo, Enrique M. and Bryja, Vítězslav and Rubin, Jeffrey S. and Shimono, Akihiko and Arenas, Ernest},
article_location = {Miamisburg, Ohio},
article_number = {5},
doi = {http://dx.doi.org/10.1002/stem.1049},
keywords = {Embryonic stem cells; Neural differentiation; Developmental biology; Parkinson's disease},
language = {eng},
issn = {1066-5099},
journal = {Stem Cells},
title = {SFRP1 and SFRP2 dose-dependently regulate midbrain dopamine neuron development in vivo and in embryonic stem cells.},
volume = {30},
year = {2012}
}
TY - JOUR
ID - 1093433
AU - Kele, Julianna - Andersson, Emma R. - Villaescusa Ramirez, Juan Carlos - Čajánek, Lukáš - Parish, Clare L. - Bonilla, Sonia - Toledo, Enrique M. - Bryja, Vítězslav - Rubin, Jeffrey S. - Shimono, Akihiko - Arenas, Ernest
PY - 2012
TI - SFRP1 and SFRP2 dose-dependently regulate midbrain dopamine neuron development in vivo and in embryonic stem cells.
JF - Stem Cells
VL - 30
IS - 5
SP - 865-875
EP - 865-875
PB - AlphaMed Press
SN - 10665099
KW - Embryonic stem cells
KW - Neural differentiation
KW - Developmental biology
KW - Parkinson's disease
N2 - 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 anteroposterior shortening of the VM, a lateral expansion of the Shh domain and DA lineage markers (Lmx1a and Th), as well as an accumulation of Nurr1+ precursors in the VM. In vitro experiments showed that, while very high concentrations of SFRP1 had a negative effect on cell survival, low/medium concentrations of sFRP1 or sFRP2 promoted the DA differentiation of progenitors derived from primary VM cultures or mouse embryonic stem cells (ESCs), mimicking the effects of Wnt5a. We thus conclude that the main function of sFRP1 and sFRP2 is to enhance Wnt/PCP signaling in DA cells and to regulate Wnt/PCP-dependent functions in midbrain development. Moreover, we suggest that low-medium concentrations of sFRPs may be used to enhance the DA differentiation of ESCs and improve their therapeutic application.
ER -
KELE, Julianna, Emma R. ANDERSSON, Juan Carlos VILLAESCUSA RAMIREZ, Lukáš ČAJÁNEK, Clare L. PARISH, Sonia BONILLA, Enrique M. TOLEDO, Vítězslav BRYJA, Jeffrey S. RUBIN, Akihiko SHIMONO a Ernest ARENAS. SFRP1 and SFRP2 dose-dependently regulate midbrain dopamine neuron development in vivo and in embryonic stem cells. \textit{Stem Cells}. Miamisburg, Ohio: AlphaMed Press, 2012, roč.~30, č.~5, s.~865-875. ISSN~1066-5099. Dostupné z: https://dx.doi.org/10.1002/stem.1049.
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