Early Transcriptional Changes Induced by Wnt/𝛽-Catenin Signaling in Hippocampal Neurons
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2016
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Facultad/escuela
Idioma
en
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Hindawi Publishing Corporation
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Atribution 4.0 International (CC BY 4.0)
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https://creativecommons.org/licenses/by/4.0/deed.es
Resumen
Wnt/𝛽-catenin signaling modulates brain development and function and its deregulation underlies pathological changes occurring
in neurodegenerative and neurodevelopmental disorders. Since one of the main effects ofWnt/𝛽-catenin signaling is the modulation
of target genes, in the present work we examined global transcriptional changes induced by short-term Wnt3a treatment (4 h)
in primary cultures of rat hippocampal neurons. RNAseq experiments allowed the identification of 170 differentially expressed
genes, including known Wnt/𝛽-catenin target genes such as Notum, Axin2, and Lef1, as well as novel potential candidates Fam84a,
Stk32a, and Itga9. Main biological processes enriched with differentially expressed genes included neural precursor (GO:0061364,
𝑝-adjusted = 2.5 × 10−7), forebrain development (GO:0030900, 𝑝-adjusted = 7.3 × 10−7), and stem cell differentiation (GO:0048863
𝑝-adjusted = 7.3 × 10−7). Likewise, following activation of the signaling cascade, the expression of a significant number of genes with
transcription factor activity (GO:0043565, 𝑝-adjusted = 4.1 × 10−6) was induced. We also studied molecular networks enriched upon
Wnt3a activation and detected three highly significant expression modules involved in glycerolipid metabolic process (GO:0046486,
𝑝-adjusted = 4.5 × 10−19), learning or memory (GO:0007611, 𝑝-adjusted = 4.0 × 10−5), and neurotransmitter secretion (GO:0007269,
𝑝-adjusted = 5.3 × 10−12). Our results indicate that Wnt/𝛽-catenin mediated transcription controls multiple biological processes
related to neuronal structure and activity that are affected in synaptic dysfunction disorders.Wnt/𝛽-catenin signaling modulates brain development and function and its deregulation underlies pathological changes occurring
in neurodegenerative and neurodevelopmental disorders. Since one of the main effects ofWnt/𝛽-catenin signaling is the modulation
of target genes, in the present work we examined global transcriptional changes induced by short-term Wnt3a treatment (4 h)
in primary cultures of rat hippocampal neurons. RNAseq experiments allowed the identification of 170 differentially expressed
genes, including known Wnt/𝛽-catenin target genes such as Notum, Axin2, and Lef1, as well as novel potential candidates Fam84a,
Stk32a, and Itga9. Main biological processes enriched with differentially expressed genes included neural precursor (GO:0061364,
𝑝-adjusted = 2.5 × 10−7), forebrain development (GO:0030900, 𝑝-adjusted = 7.3 × 10−7), and stem cell differentiation (GO:0048863
𝑝-adjusted = 7.3 × 10−7). Likewise, following activation of the signaling cascade, the expression of a significant number of genes with
transcription factor activity (GO:0043565, 𝑝-adjusted = 4.1 × 10−6) was induced. We also studied molecular networks enriched upon
Wnt3a activation and detected three highly significant expression modules involved in glycerolipid metabolic process (GO:0046486,
𝑝-adjusted = 4.5 × 10−19), learning or memory (GO:0007611, 𝑝-adjusted = 4.0 × 10−5), and neurotransmitter secretion (GO:0007269,
𝑝-adjusted = 5.3 × 10−12). Our results indicate that Wnt/𝛽-catenin mediated transcription controls multiple biological processes
related to neuronal structure and activity that are affected in synaptic dysfunction disorders.
Notas
Indexación: Scopus.
Palabras clave
Hippocampal Neurons, Neurodevelopmental Disorders
Citación
Neural Plasticity. Volume 2016. 2016. Article number 4672841
DOI
10.1155/2016/4672841