Early Transcriptional Changes Induced by Wnt/β-Catenin Signaling in Hippocampal Neurons
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 of Wnt/β-catenin signaling is the modulation of target genes, in the present work we exa...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2016/4672841 |
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| author | Eduardo Pérez-Palma Víctor Andrade Mario O. Caracci Bernabé I. Bustos Camilo Villaman Matías A. Medina Miguel E. Ávila Giorgia D. Ugarte Giancarlo V. De Ferrari |
| author_facet | Eduardo Pérez-Palma Víctor Andrade Mario O. Caracci Bernabé I. Bustos Camilo Villaman Matías A. Medina Miguel E. Ávila Giorgia D. Ugarte Giancarlo V. De Ferrari |
| author_sort | Eduardo Pérez-Palma |
| collection | DOAJ |
| description | 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 of Wnt/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. |
| format | Article |
| id | doaj-art-35d08dd20a6440888802026ac09217a0 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-35d08dd20a6440888802026ac09217a02025-02-03T01:01:08ZengWileyNeural Plasticity2090-59041687-54432016-01-01201610.1155/2016/46728414672841Early Transcriptional Changes Induced by Wnt/β-Catenin Signaling in Hippocampal NeuronsEduardo Pérez-Palma0Víctor Andrade1Mario O. Caracci2Bernabé I. Bustos3Camilo Villaman4Matías A. Medina5Miguel E. Ávila6Giorgia D. Ugarte7Giancarlo V. De Ferrari8Centro de Investigaciones Biomédicas (CIB), Facultad de Ciencias Biológicas y Facultad de Medicina, Universidad Andres Bello, Santiago, ChileCentro de Investigaciones Biomédicas (CIB), Facultad de Ciencias Biológicas y Facultad de Medicina, Universidad Andres Bello, Santiago, ChileCentro de Investigaciones Biomédicas (CIB), Facultad de Ciencias Biológicas y Facultad de Medicina, Universidad Andres Bello, Santiago, ChileCentro de Investigaciones Biomédicas (CIB), Facultad de Ciencias Biológicas y Facultad de Medicina, Universidad Andres Bello, Santiago, ChileCentro de Investigaciones Biomédicas (CIB), Facultad de Ciencias Biológicas y Facultad de Medicina, Universidad Andres Bello, Santiago, ChileCentro de Investigaciones Biomédicas (CIB), Facultad de Ciencias Biológicas y Facultad de Medicina, Universidad Andres Bello, Santiago, ChileCentro de Investigaciones Biomédicas (CIB), Facultad de Ciencias Biológicas y Facultad de Medicina, Universidad Andres Bello, Santiago, ChileCentro de Investigaciones Biomédicas (CIB), Facultad de Ciencias Biológicas y Facultad de Medicina, Universidad Andres Bello, Santiago, ChileCentro de Investigaciones Biomédicas (CIB), Facultad de Ciencias Biológicas y Facultad de Medicina, Universidad Andres Bello, Santiago, ChileWnt/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 of Wnt/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.http://dx.doi.org/10.1155/2016/4672841 |
| spellingShingle | Eduardo Pérez-Palma Víctor Andrade Mario O. Caracci Bernabé I. Bustos Camilo Villaman Matías A. Medina Miguel E. Ávila Giorgia D. Ugarte Giancarlo V. De Ferrari Early Transcriptional Changes Induced by Wnt/β-Catenin Signaling in Hippocampal Neurons Neural Plasticity |
| title | Early Transcriptional Changes Induced by Wnt/β-Catenin Signaling in Hippocampal Neurons |
| title_full | Early Transcriptional Changes Induced by Wnt/β-Catenin Signaling in Hippocampal Neurons |
| title_fullStr | Early Transcriptional Changes Induced by Wnt/β-Catenin Signaling in Hippocampal Neurons |
| title_full_unstemmed | Early Transcriptional Changes Induced by Wnt/β-Catenin Signaling in Hippocampal Neurons |
| title_short | Early Transcriptional Changes Induced by Wnt/β-Catenin Signaling in Hippocampal Neurons |
| title_sort | early transcriptional changes induced by wnt β catenin signaling in hippocampal neurons |
| url | http://dx.doi.org/10.1155/2016/4672841 |
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