| ANDERSSON, Emma R., Carmen SALTO, Juan Carlos VILLAESCUSA RAMIREZ, Lukáš ČAJÁNEK, Shanzheng YANG, Lenka BRYJOVÁ, Irina NAGI, Seppo J. VAINIO, Carmen RAMIREZ, Vítězslav BRYJA and Ernest ARENAS. Wnt5a cooperates with canonical Wnts to generate midbrain dopaminergic neurons in vivo and in stem cells. Proceedings of the National Academy of Sciences of the United States of America. WASHINGTON: NATL ACAD SCIENCES, 2013, vol. 110, No 7, p. E602–E610, 9 pp. ISSN 0027-8424. Available from: https://dx.doi.org/10.1073/pnas.1208524110. |
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@article{1093426,
author = {Andersson, Emma R. and Salto, Carmen and Villaescusa Ramirez, Juan Carlos and Čajánek, Lukáš and Yang, Shanzheng and Bryjová, Lenka and Nagi, Irina and Vainio, Seppo J. and Ramirez, Carmen and Bryja, Vítězslav and Arenas, Ernest},
article_location = {WASHINGTON},
article_number = {7},
doi = {http://dx.doi.org/10.1073/pnas.1208524110},
keywords = {ES cell; Wnt3a; Mash1; Foxa2; Pitx3},
language = {eng},
issn = {0027-8424},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
title = {Wnt5a cooperates with canonical Wnts to generate midbrain dopaminergic neurons in vivo and in stem cells.},
url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3574960/},
volume = {110},
year = {2013}
}
TY - JOUR
ID - 1093426
AU - Andersson, Emma R. - Salto, Carmen - Villaescusa Ramirez, Juan Carlos - Čajánek, Lukáš - Yang, Shanzheng - Bryjová, Lenka - Nagi, Irina - Vainio, Seppo J. - Ramirez, Carmen - Bryja, Vítězslav - Arenas, Ernest
PY - 2013
TI - Wnt5a cooperates with canonical Wnts to generate midbrain dopaminergic neurons in vivo and in stem cells.
JF - Proceedings of the National Academy of Sciences of the United States of America
VL - 110
IS - 7
SP - E602–E610
EP - E602–E610
PB - NATL ACAD SCIENCES
SN - 00278424
KW - ES cell
KW - Wnt3a
KW - Mash1
KW - Foxa2
KW - Pitx3
UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3574960/
N2 - Wnts are a family of secreted proteins that regulate multiple steps of neural development and stem cell differentiation. Two of them, Wnt1 and Wnt5a, activate distinct branches of Wnt signaling and individually regulate different aspects of midbrain dopaminergic (DA) neuron development. However, several of their functions and interactions remain to be elucidated. Here, we report that loss of Wnt1 results in loss of Lmx1a and Ngn2 expression, as well as agenesis of DA neurons in the midbrain floor plate. Remarkably, a few ectopic DA neurons still emerge in the basal plate of Wnt1 mice, where Lmx1a is ectopically expressed. These results indicate that Wnt1 orchestrates DA specification and neurogenesis in vivo. Analysis of Wnt1; Wnt5a mice revealed a greater loss of Nurr1+ cells and DA neurons than in single mutants, indicating that Wnt1 and Wnt5a interact genetically and cooperate to promote midbrain DA neuron development in vivo. Our results unravel a functional interaction between Wnt1 and Wnt5a resulting in enhanced DA neurogenesis. Taking advantage of these findings, we have developed an application of Wnts to improve the generation of midbrain DA neurons from neural and embryonic stem cells. We thus show that coordinated Wnt actions promote DA neuron development in vivo and in stem cells and suggest that coordinated Wnt administration can be used to improve DA differentiation of stem cells and the development of stem cell-based therapies for Parkinson’s disease.
ER -
ANDERSSON, Emma R., Carmen SALTO, Juan Carlos VILLAESCUSA RAMIREZ, Lukáš ČAJÁNEK, Shanzheng YANG, Lenka BRYJOVÁ, Irina NAGI, Seppo J. VAINIO, Carmen RAMIREZ, Vítězslav BRYJA and Ernest ARENAS. Wnt5a cooperates with canonical Wnts to generate midbrain dopaminergic neurons in vivo and in stem cells. \textit{Proceedings of the National Academy of Sciences of the United States of America}. WASHINGTON: NATL ACAD SCIENCES, 2013, vol.~110, No~7, p.~E602–E610, 9 pp. ISSN~0027-8424. Available from: https://dx.doi.org/10.1073/pnas.1208524110.
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