2013
Wnt5a cooperates with canonical Wnts to generate midbrain dopaminergic neurons in vivo and in stem cells.
ANDERSSON, Emma R., Carmen SALTO, Juan Carlos VILLAESCUSA RAMIREZ, Lukáš ČAJÁNEK, Shanzheng YANG et. al.Základní údaje
Originální název
Wnt5a cooperates with canonical Wnts to generate midbrain dopaminergic neurons in vivo and in stem cells.
Autoři
ANDERSSON, Emma R. (752 Švédsko), Carmen SALTO (724 Španělsko), Juan Carlos VILLAESCUSA RAMIREZ (724 Španělsko), Lukáš ČAJÁNEK (203 Česká republika), Shanzheng YANG (156 Čína), Lenka BRYJOVÁ (203 Česká republika, domácí), Irina NAGI (246 Finsko), Seppo J. VAINIO (246 Finsko), Carmen RAMIREZ (724 Španělsko), Vítězslav BRYJA (203 Česká republika, garant, domácí) a Ernest ARENAS (724 Španělsko)
Vydání
Proceedings of the National Academy of Sciences of the United States of America, WASHINGTON, NATL ACAD SCIENCES, 2013, 0027-8424
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30105 Physiology
Stát vydavatele
Spojené státy
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 9.809
Kód RIV
RIV/00216224:14310/13:00066064
Organizační jednotka
Přírodovědecká fakulta
UT WoS
000315812800009
Klíčová slova anglicky
ES cell; Wnt3a; Mash1; Foxa2; Pitx3
Změněno: 10. 3. 2015 13:51, Mgr. et Mgr. Veronika Oškerová, Ph.D.
Anotace
V originále
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.
Návaznosti
GAP301/11/0747, projekt VaV |
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GA204/09/0498, projekt VaV |
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