TY - JOUR
T1 - Frizzled-1 receptor regulates adult hippocampal neurogenesis
AU - Mardones, Muriel D.
AU - Andaur, Gabriela A.
AU - Varas-Godoy, Manuel
AU - Henriquez, Jenny F.
AU - Salech, Felipe
AU - Behrens, María Isabel
AU - Couve, Andrés
AU - Inestrosa, Nibaldo C.
AU - Varela-Nallar, Lorena
N1 - Funding Information:
This work was supported by grants from ICM P09-015-F to A.C. and F.S; FON-DECYT (N°1120156) and the Basal Center of Excellence in Science and Technology (CONICYT-PFB12/2007) to N.C.I.; FONDECYT (N°1150933) to L.V-N.
Publisher Copyright:
© 2016 Mardones et al.
PY - 2016/3/15
Y1 - 2016/3/15
N2 - Background: In the adult hippocampus new neurons are continuously generated from neural stem cells (NSCs) present at the subgranular zone of the dentate gyrus. This process is controlled by Wnt signaling, which plays a complex role in regulating multiple steps of neurogenesis including maintenance, proliferation and differentiation of progenitor cells and the development of newborn neurons. Differential effects of Wnt signaling during progression of neurogenesis could be mediated by cell-type specific expression of Wnt receptors. Here we studied the potential role of Frizzled-1 (FZD1) receptor in adult hippocampal neurogenesis. Results: In the adult dentate gyrus, we determined that FZD1 is highly expressed in NSCs, neural progenitors and immature neurons. Accordingly, FZD1 is expressed in cultured adult hippocampal progenitors isolated from mouse brain. To evaluate the role of this receptor in vivo we targeted FZD1 in newborn cells using retroviral-mediated RNA interference. FZD1 knockdown resulted in a marked decrease in the differentiation of newborn cells into neurons and increased the generation of astrocytes, suggesting a regulatory role for the receptor in cell fate commitment. In addition, FZD1 knockdown induced an extended migration of adult-born neurons within the granule cell layer. However, no differences were observed in total dendritic length and dendritic arbor complexity between control and FZD1-deficient newborn neurons. Conclusions: Our results show that FZD1 regulates specific stages of adult hippocampal neurogenesis, being required for neuronal differentiation and positioning of newborn neurons into the granule cell layer, but not for morphological development of adult-born granule neurons.
AB - Background: In the adult hippocampus new neurons are continuously generated from neural stem cells (NSCs) present at the subgranular zone of the dentate gyrus. This process is controlled by Wnt signaling, which plays a complex role in regulating multiple steps of neurogenesis including maintenance, proliferation and differentiation of progenitor cells and the development of newborn neurons. Differential effects of Wnt signaling during progression of neurogenesis could be mediated by cell-type specific expression of Wnt receptors. Here we studied the potential role of Frizzled-1 (FZD1) receptor in adult hippocampal neurogenesis. Results: In the adult dentate gyrus, we determined that FZD1 is highly expressed in NSCs, neural progenitors and immature neurons. Accordingly, FZD1 is expressed in cultured adult hippocampal progenitors isolated from mouse brain. To evaluate the role of this receptor in vivo we targeted FZD1 in newborn cells using retroviral-mediated RNA interference. FZD1 knockdown resulted in a marked decrease in the differentiation of newborn cells into neurons and increased the generation of astrocytes, suggesting a regulatory role for the receptor in cell fate commitment. In addition, FZD1 knockdown induced an extended migration of adult-born neurons within the granule cell layer. However, no differences were observed in total dendritic length and dendritic arbor complexity between control and FZD1-deficient newborn neurons. Conclusions: Our results show that FZD1 regulates specific stages of adult hippocampal neurogenesis, being required for neuronal differentiation and positioning of newborn neurons into the granule cell layer, but not for morphological development of adult-born granule neurons.
KW - Adult neurogenesis
KW - Frizzled
KW - Hippocampus
KW - Neural progenitor cells
KW - Neuronal differentiation
KW - Wnt signaling
UR - http://www.scopus.com/inward/record.url?scp=84961204099&partnerID=8YFLogxK
U2 - 10.1186/s13041-016-0209-3
DO - 10.1186/s13041-016-0209-3
M3 - Article
C2 - 26980182
AN - SCOPUS:84961204099
SN - 1756-6606
VL - 9
JO - Molecular Brain
JF - Molecular Brain
IS - 1
M1 - 209
ER -