TY - JOUR
T1 - Wnt5a promotes differentiation and development of adult-born neurons in the hippocampus by noncanonical Wnt signaling
AU - Arredondo, Sebastian B.
AU - Guerrero, Fernanda G.
AU - Herrera-Soto, Andrea
AU - Jensen-Flores, Joaquin
AU - Bustamante, Daniel B.
AU - Oñate-Ponce, Alejandro
AU - Henny, Pablo
AU - Varas-Godoy, Manuel
AU - Inestrosa, Nibaldo C.
AU - Varela-Nallar, Lorena
N1 - Funding Information:
This work was supported by grants from Fondecyt No. 1150933 and No. 1190461 (L.V.-N.), Fondecyt No. 1141170 (P.H.), Nucleo UNAB DI-4-17/N (L.V-N.), Conicyt Anillo ACT1109 (P.H.), CARE-UC Conicyt-AFB 170005 (N.C.I.), pre-doctoral Fellowship from Fondecyt No. 21151115 (S.B.A.). All authors declare nonfinancial competing interests.
Funding Information:
This work was supported by grants from Fondecyt No. 1150933 and No. 1190461 (L.V.‐N.), Fondecyt No. 1141170 (P.H.), Nucleo UNAB DI‐4‐17/N (L.V‐N.), Conicyt Anillo ACT1109 (P.H.), CARE‐UC Conicyt‐AFB 170005 (N.C.I.), pre‐doctoral Fellowship from Fondecyt No. 21151115 (S.B.A.). All authors declare nonfinancial competing interests.
Publisher Copyright:
©AlphaMed Press 2019
PY - 2019/1/1
Y1 - 2019/1/1
N2 - In the adult hippocampus, new neurons are generated in the dentate gyrus. The Wnt signaling pathway regulates this process, but little is known about the endogenous Wnt ligands involved. We investigated the role of Wnt5a on adult hippocampal neurogenesis. Wnt5a regulates neuronal morphogenesis during embryonic development, and maintains dendritic architecture of pyramidal neurons in the adult hippocampus. Here, we determined that Wnt5a knockdown in the mouse dentate gyrus by lentivirus-mediated shRNA impaired neuronal differentiation of progenitor cells, and reduced dendritic development of adult-born neurons. In cultured adult hippocampal progenitors (AHPs), Wnt5a knockdown reduced neuronal differentiation and morphological development of AHP-derived neurons, whereas treatment with Wnt5a had the opposite effect. Interestingly, no changes in astrocytic differentiation were observed in vivo or in vitro, suggesting that Wnt5a does not affect fate-commitment. By using specific inhibitors, we determined that Wnt5a signals through CaMKII to induce neurogenesis, and promotes dendritic development of newborn neurons through activating Wnt/JNK and Wnt/CaMKII signaling. Our results indicate Wnt5a as a niche factor in the adult hippocampus that promotes neuronal differentiation and development through activation of noncanonical Wnt signaling pathways.
AB - In the adult hippocampus, new neurons are generated in the dentate gyrus. The Wnt signaling pathway regulates this process, but little is known about the endogenous Wnt ligands involved. We investigated the role of Wnt5a on adult hippocampal neurogenesis. Wnt5a regulates neuronal morphogenesis during embryonic development, and maintains dendritic architecture of pyramidal neurons in the adult hippocampus. Here, we determined that Wnt5a knockdown in the mouse dentate gyrus by lentivirus-mediated shRNA impaired neuronal differentiation of progenitor cells, and reduced dendritic development of adult-born neurons. In cultured adult hippocampal progenitors (AHPs), Wnt5a knockdown reduced neuronal differentiation and morphological development of AHP-derived neurons, whereas treatment with Wnt5a had the opposite effect. Interestingly, no changes in astrocytic differentiation were observed in vivo or in vitro, suggesting that Wnt5a does not affect fate-commitment. By using specific inhibitors, we determined that Wnt5a signals through CaMKII to induce neurogenesis, and promotes dendritic development of newborn neurons through activating Wnt/JNK and Wnt/CaMKII signaling. Our results indicate Wnt5a as a niche factor in the adult hippocampus that promotes neuronal differentiation and development through activation of noncanonical Wnt signaling pathways.
KW - adult neurogenesis
KW - differentiation
KW - hippocampus
KW - Wnt signaling
KW - Wnt5a
UR - http://www.scopus.com/inward/record.url?scp=85075432812&partnerID=8YFLogxK
U2 - 10.1002/stem.3121
DO - 10.1002/stem.3121
M3 - Article
C2 - 31721364
AN - SCOPUS:85075432812
SN - 1066-5099
VL - 38
SP - 422
EP - 436
JO - Stem Cells
JF - Stem Cells
IS - 3
ER -