title: Frizzled-1 receptor regulates adult hippocampal neurogenesis.
abstract: 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.
authors.affiliation: Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, Santiago, Chile.
authors.forename: Muriel D
authors.initials: MD
authors.lastname: Mardones
authors.affiliation: Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, Santiago, Chile.
authors.forename: Gabriela A
authors.initials: GA
authors.lastname: Andaur
authors.affiliation: Centro de Investigación Biomédica, Facultad de Medicina, Universidad de los Andes, Santiago, Chile.
authors.forename: Manuel
authors.initials: M
authors.lastname: Varas-Godoy
authors.affiliation: Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, Santiago, Chile.
authors.forename: Jenny F
authors.initials: JF
authors.lastname: Henriquez
authors.affiliation: Unidad de Geriatría, Hospital Clínico Universidad de Chile, Santiago, Chile.|Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Felipe
authors.initials: F
authors.lastname: Salech
authors.affiliation: Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile.|Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile.|Clínica Alemana de Santiago, Santiago, Chile.
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Behrens
authors.affiliation: Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile.|Biomedical Neuroscience Institute (BNI), Santiago, Chile.
authors.forename: Andrés
authors.initials: A
authors.lastname: Couve
authors.affiliation: Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago, Chile.|Center for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia.|Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile.
authors.forename: Nibaldo C
authors.initials: NC
authors.lastname: Inestrosa
authors.affiliation: Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, Santiago, Chile. lorena.varela@unab.cl.
authors.forename: Lorena
authors.initials: L
authors.lastname: Varela-Nallar
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D002465:Cell Movement; D003712:Dendrites / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism; D051157:Frizzled Receptors / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis
chemical_list: D051157:Frizzled Receptors; C489739:Fzd1 protein, mouse
keywords: Adult neurogenesis; Frizzled; Hippocampus; Neural progenitor cells; Neuronal differentiation; Wnt signaling