Frizzled-1 receptor regulates adult hippocampal neurogenesis

Muriel D. Mardones, Gabriela A. Andaur, Manuel Varas-Godoy, Jenny F. Henriquez, Felipe Salech, María Isabel Behrens, Andrés Couve, Nibaldo C. Inestrosa, Lorena Varela-Nallar

Resultado de la investigación: Article

15 Citas (Scopus)

Resumen

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.

Idioma originalEnglish
Número de artículo209
PublicaciónMolecular Brain
Volumen9
N.º1
DOI
EstadoPublished - 15 mar 2016

Huella dactilar

Frizzled Receptors
Neurogenesis
Neurons
Neural Stem Cells
Dentate Gyrus
Wnt Receptors
RNA Interference
Astrocytes
Cell Differentiation
Hippocampus
Stem Cells
Maintenance

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Citar esto

Mardones, M. D., Andaur, G. A., Varas-Godoy, M., Henriquez, J. F., Salech, F., Behrens, M. I., ... Varela-Nallar, L. (2016). Frizzled-1 receptor regulates adult hippocampal neurogenesis. Molecular Brain, 9(1), [209]. https://doi.org/10.1186/s13041-016-0209-3
Mardones, Muriel D. ; Andaur, Gabriela A. ; Varas-Godoy, Manuel ; Henriquez, Jenny F. ; Salech, Felipe ; Behrens, María Isabel ; Couve, Andrés ; Inestrosa, Nibaldo C. ; Varela-Nallar, Lorena. / Frizzled-1 receptor regulates adult hippocampal neurogenesis. En: Molecular Brain. 2016 ; Vol. 9, N.º 1.
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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.",
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Mardones, MD, Andaur, GA, Varas-Godoy, M, Henriquez, JF, Salech, F, Behrens, MI, Couve, A, Inestrosa, NC & Varela-Nallar, L 2016, 'Frizzled-1 receptor regulates adult hippocampal neurogenesis', Molecular Brain, vol. 9, n.º 1, 209. https://doi.org/10.1186/s13041-016-0209-3

Frizzled-1 receptor regulates adult hippocampal neurogenesis. / Mardones, Muriel D.; Andaur, Gabriela A.; Varas-Godoy, Manuel; Henriquez, Jenny F.; Salech, Felipe; Behrens, María Isabel; Couve, Andrés; Inestrosa, Nibaldo C.; Varela-Nallar, Lorena.

En: Molecular Brain, Vol. 9, N.º 1, 209, 15.03.2016.

Resultado de la investigación: Article

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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

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.

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Mardones MD, Andaur GA, Varas-Godoy M, Henriquez JF, Salech F, Behrens MI y otros. Frizzled-1 receptor regulates adult hippocampal neurogenesis. Molecular Brain. 2016 mar 15;9(1). 209. https://doi.org/10.1186/s13041-016-0209-3