Chromatin Remodeler CHD8 in Autism and Brain Development
Chromodomain Helicase DNA-binding 8 (<i>CHD8</i>) is a high confidence risk factor for autism spectrum disorders (ASDs) and the genetic cause of a distinct neurodevelopmental syndrome with the core symptoms of autism, macrocephaly, and facial dysmorphism. The role of <i>CHD8</i&...
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| Format: | Article |
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MDPI AG
2021-01-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/10/2/366 |
| _version_ | 1797409739862179840 |
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| author | Anke Hoffmann Dietmar Spengler |
| author_facet | Anke Hoffmann Dietmar Spengler |
| author_sort | Anke Hoffmann |
| collection | DOAJ |
| description | Chromodomain Helicase DNA-binding 8 (<i>CHD8</i>) is a high confidence risk factor for autism spectrum disorders (ASDs) and the genetic cause of a distinct neurodevelopmental syndrome with the core symptoms of autism, macrocephaly, and facial dysmorphism. The role of <i>CHD8</i> is well-characterized at the structural, biochemical, and transcriptional level. By contrast, much less is understood regarding how mutations in <i>CHD8</i> underpin altered brain function and mental disease. Studies on various model organisms have been proven critical to tackle this challenge. Here, we scrutinize recent advances in this field with a focus on phenotypes in transgenic animal models and highlight key findings on neurodevelopment, neuronal connectivity, neurotransmission, synaptic and homeostatic plasticity, and habituation. Against this backdrop, we further discuss how to improve future animal studies, both in terms of technical issues and with respect to the sex-specific effects of <i>Chd8</i> mutations for neuronal and higher-systems level function. We also consider outstanding questions in the field including ‘humanized’ mice models, therapeutic interventions, and how the use of pluripotent stem cell-derived cerebral organoids might help to address differences in neurodevelopment trajectories between model organisms and humans. |
| first_indexed | 2024-03-09T04:18:53Z |
| format | Article |
| id | doaj.art-4df0722e0c3a4ef185b30287a11f8c17 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T04:18:53Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-4df0722e0c3a4ef185b30287a11f8c172023-12-03T13:49:24ZengMDPI AGJournal of Clinical Medicine2077-03832021-01-0110236610.3390/jcm10020366Chromatin Remodeler CHD8 in Autism and Brain DevelopmentAnke Hoffmann0Dietmar Spengler1Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, 80804 Munich, GermanyDepartment of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, 80804 Munich, GermanyChromodomain Helicase DNA-binding 8 (<i>CHD8</i>) is a high confidence risk factor for autism spectrum disorders (ASDs) and the genetic cause of a distinct neurodevelopmental syndrome with the core symptoms of autism, macrocephaly, and facial dysmorphism. The role of <i>CHD8</i> is well-characterized at the structural, biochemical, and transcriptional level. By contrast, much less is understood regarding how mutations in <i>CHD8</i> underpin altered brain function and mental disease. Studies on various model organisms have been proven critical to tackle this challenge. Here, we scrutinize recent advances in this field with a focus on phenotypes in transgenic animal models and highlight key findings on neurodevelopment, neuronal connectivity, neurotransmission, synaptic and homeostatic plasticity, and habituation. Against this backdrop, we further discuss how to improve future animal studies, both in terms of technical issues and with respect to the sex-specific effects of <i>Chd8</i> mutations for neuronal and higher-systems level function. We also consider outstanding questions in the field including ‘humanized’ mice models, therapeutic interventions, and how the use of pluripotent stem cell-derived cerebral organoids might help to address differences in neurodevelopment trajectories between model organisms and humans.https://www.mdpi.com/2077-0383/10/2/366autismneurodevelopmental disorderschromatin regulationneurodevelopmentneuronal connectivityneurotransmission |
| spellingShingle | Anke Hoffmann Dietmar Spengler Chromatin Remodeler CHD8 in Autism and Brain Development Journal of Clinical Medicine autism neurodevelopmental disorders chromatin regulation neurodevelopment neuronal connectivity neurotransmission |
| title | Chromatin Remodeler CHD8 in Autism and Brain Development |
| title_full | Chromatin Remodeler CHD8 in Autism and Brain Development |
| title_fullStr | Chromatin Remodeler CHD8 in Autism and Brain Development |
| title_full_unstemmed | Chromatin Remodeler CHD8 in Autism and Brain Development |
| title_short | Chromatin Remodeler CHD8 in Autism and Brain Development |
| title_sort | chromatin remodeler chd8 in autism and brain development |
| topic | autism neurodevelopmental disorders chromatin regulation neurodevelopment neuronal connectivity neurotransmission |
| url | https://www.mdpi.com/2077-0383/10/2/366 |
| work_keys_str_mv | AT ankehoffmann chromatinremodelerchd8inautismandbraindevelopment AT dietmarspengler chromatinremodelerchd8inautismandbraindevelopment |