Wnt5a promotes differentiation and development of adult-born neurons in the hippocampus by noncanonical Wnt signaling

Arredondo S.B.; Guerrero F.G.; Herrera-Soto A.; Jensen-Flores J.; Bustamante D.B.; Oñate-Ponce A.; Henny P.; Varas-Godoy M.; Inestrosa N.C.; Varela-Nallar L.

Abstract

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

Más información

Título según WOS: Wnt5a promotes differentiation and development of adult-born neurons in the hippocampus by noncanonical Wnt signaling
Título según SCOPUS: Wnt5a promotes differentiation and development of adult-born neurons in the hippocampus by noncanonical Wnt signaling
Título de la Revista: STEM CELLS
Volumen: 38
Número: 3
Editorial: Wiley
Fecha de publicación: 2020
Página de inicio: 422
Página final: 436
Idioma: English
DOI:

10.1002/stem.3121

Notas: ISI, SCOPUS