Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling
De novo mutations in CHD8 are strongly associated with autism spectrum disorder, but the basic biology of CHD8 remains poorly understood. Here we report that Chd8 knockdown during cortical development results in defective neural progenitor proliferation and differentiation that ultimately manifests...
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| Format: | Article |
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Nature Publishing Group
2017
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| Online Access: | http://hdl.handle.net/1721.1/112696 https://orcid.org/0000-0001-8426-6188 https://orcid.org/0000-0001-9225-3221 https://orcid.org/0000-0002-2206-2590 https://orcid.org/0000-0002-2029-7193 https://orcid.org/0000-0003-1262-0592 |
| _version_ | 1810991091670843392 |
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| author | Durak, Omer Gao, Fan Kaeser-Woo, Yea Jin Rueda IV, Richard Martorell, Anthony Nott, Alexander Liu, Carol Y Watson, Lauren Ashley Tsai, Li-Huei |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Durak, Omer Gao, Fan Kaeser-Woo, Yea Jin Rueda IV, Richard Martorell, Anthony Nott, Alexander Liu, Carol Y Watson, Lauren Ashley Tsai, Li-Huei |
| author_sort | Durak, Omer |
| collection | MIT |
| description | De novo mutations in CHD8 are strongly associated with autism spectrum disorder, but the basic biology of CHD8 remains poorly understood. Here we report that Chd8 knockdown during cortical development results in defective neural progenitor proliferation and differentiation that ultimately manifests in abnormal neuronal morphology and behaviors in adult mice. Transcriptome analysis revealed that while Chd8 stimulates the transcription of cell cycle genes, it also precludes the induction of neural-specific genes by regulating the expression of PRC2 complex components. Furthermore, knockdown of Chd8 disrupts the expression of key transducers of Wnt signaling, and enhancing Wnt signaling rescues the transcriptional and behavioral deficits caused by Chd8 knockdown. We propose that these roles of Chd8 and the dynamics of Chd8 expression during development help negotiate the fine balance between neural progenitor proliferation and differentiation. Together, these observations provide new insights into the neurodevelopmental role of Chd8. |
| first_indexed | 2024-09-23T12:48:11Z |
| format | Article |
| id | mit-1721.1/112696 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T12:48:11Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1126962022-09-28T10:08:58Z Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling Durak, Omer Gao, Fan Kaeser-Woo, Yea Jin Rueda IV, Richard Martorell, Anthony Nott, Alexander Liu, Carol Y Watson, Lauren Ashley Tsai, Li-Huei Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Durak, Omer Gao, Fan Kaeser-Woo, Yea Jin Rueda IV, Richard Martorell, Anthony Nott, Alexander Liu, Carol Y Watson, Lauren Ashley Tsai, Li-Huei De novo mutations in CHD8 are strongly associated with autism spectrum disorder, but the basic biology of CHD8 remains poorly understood. Here we report that Chd8 knockdown during cortical development results in defective neural progenitor proliferation and differentiation that ultimately manifests in abnormal neuronal morphology and behaviors in adult mice. Transcriptome analysis revealed that while Chd8 stimulates the transcription of cell cycle genes, it also precludes the induction of neural-specific genes by regulating the expression of PRC2 complex components. Furthermore, knockdown of Chd8 disrupts the expression of key transducers of Wnt signaling, and enhancing Wnt signaling rescues the transcriptional and behavioral deficits caused by Chd8 knockdown. We propose that these roles of Chd8 and the dynamics of Chd8 expression during development help negotiate the fine balance between neural progenitor proliferation and differentiation. Together, these observations provide new insights into the neurodevelopmental role of Chd8. National Institutes of Health (U.S.) (Grant UH1-MH106018-03) 2017-12-11T20:41:23Z 2017-12-11T20:41:23Z 2016-10 2015-11 2017-12-11T19:36:19Z Article http://purl.org/eprint/type/JournalArticle 1097-6256 1546-1726 http://hdl.handle.net/1721.1/112696 Durak, Omer et al. “Chd8 Mediates Cortical Neurogenesis via Transcriptional Regulation of Cell Cycle and Wnt Signaling.” Nature Neuroscience 19, 11 (October 2016): 1477–1488 © Nature America, Inc, part of Springer Nature https://orcid.org/0000-0001-8426-6188 https://orcid.org/0000-0001-9225-3221 https://orcid.org/0000-0002-2206-2590 https://orcid.org/0000-0002-2029-7193 https://orcid.org/0000-0003-1262-0592 http://dx.doi.org/10.1038/NN.4400 Nature Neuroscience Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group PMC |
| spellingShingle | Durak, Omer Gao, Fan Kaeser-Woo, Yea Jin Rueda IV, Richard Martorell, Anthony Nott, Alexander Liu, Carol Y Watson, Lauren Ashley Tsai, Li-Huei Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling |
| title | Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling |
| title_full | Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling |
| title_fullStr | Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling |
| title_full_unstemmed | Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling |
| title_short | Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling |
| title_sort | chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and wnt signaling |
| url | http://hdl.handle.net/1721.1/112696 https://orcid.org/0000-0001-8426-6188 https://orcid.org/0000-0001-9225-3221 https://orcid.org/0000-0002-2206-2590 https://orcid.org/0000-0002-2029-7193 https://orcid.org/0000-0003-1262-0592 |
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