Wnt5a cooperates with canonical Wnts to generate midbrain
dopaminergic neurons in vivo and in stem cells.

J 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.

Basic information

Original name

Wnt5a cooperates with canonical Wnts to generate midbrain dopaminergic neurons in vivo and in stem cells.

Authors

ANDERSSON, Emma R. (752 Sweden), Carmen SALTO (724 Spain), Juan Carlos VILLAESCUSA RAMIREZ (724 Spain), Lukáš ČAJÁNEK (203 Czech Republic), Shanzheng YANG (156 China), Lenka BRYJOVÁ (203 Czech Republic, belonging to the institution), Irina NAGI (246 Finland), Seppo J. VAINIO (246 Finland), Carmen RAMIREZ (724 Spain), Vítězslav BRYJA (203 Czech Republic, guarantor, belonging to the institution) and Ernest ARENAS (724 Spain)

Edition

Proceedings of the National Academy of Sciences of the United States of America, WASHINGTON, NATL ACAD SCIENCES, 2013, 0027-8424

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30105 Physiology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 9.809

RIV identification code

RIV/00216224:14310/13:00066064

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1073/pnas.1208524110

UT WoS

000315812800009

Keywords in English

ES cell; Wnt3a; Mash1; Foxa2; Pitx3

Abstract

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.

Links

GAP301/11/0747, research and development project

Name: Molekulární mechanismy nekanonické Wnt signalizace v leukémii

Investor: Czech Science Foundation

GA204/09/0498, research and development project

Name: Dynamika proteinů interagujících s Dishevelled a jejich význam pro Wnt signálování

Investor: Czech Science Foundation, Dynamics of proteins interacting with Dishevelled and their importance for Wnt signalling

Citovat

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.

@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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