| dc.identifier.uri | http://hdl.handle.net/11401/77828 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.abstract | The phenomenon of incomplete penetrance occurs when individuals carrying a disease-causing allele fail to express the trait. While incomplete penetrance is prevalent in neurodevelopmental/neuropsychiatric syndromes and often confounds diagnosis and treatment, the mechanisms responsible are poorly understood. A deficiency in the neuron-specific tumor suppressor Chd5 causes alterations in behavior and dendritic morphology, and these phenotypes are incompletely penetrant in heterozygotes. CHD5 is a predicted chromatin remodeling protein of the SWI/SNF superfamily that was previously identified as a tumor suppressor mapping to human 1p36, a region of the genome frequently deleted in neuronal malignancies. Chd5 is expressed throughout the brain, with expression being particularly robust in post-mitotic differentiated neurons. Chd5-deficiency causes striking phenotypes including hyperactivity, repetitive behavior, and abnormal dendritic morphology of cortical pyramidal neurons. Interestingly, the phenotypes of Chd5+/- mice are incompletely penetrant, as only a subset have these behavioral and dendritic impairments. Chd5 regulates expression of specific genes that play a key role in neurodevelopment, thereby providing a mechanistic link between Chd5 and the observed phenotypes in Chd5-compromised mice. These findings reveal a role for Chd5 in neuronal function in vivo and highlight the critical role of threshold levels of chromatin modifiers in regulating gene expression cascades critical to neuronal connectivity and brain function. | |
| dcterms.available | 2017-09-26T17:10:15Z | |
| dcterms.contributor | Mills, Alea A | en_US |
| dcterms.contributor | Holdener, Bernadette | en_US |
| dcterms.contributor | Spector, David | en_US |
| dcterms.contributor | Enikolopov, Grigori | en_US |
| dcterms.contributor | Bernstein, Emily. | en_US |
| dcterms.creator | Vestin, Assaf | |
| dcterms.dateAccepted | 2017-09-26T17:10:15Z | |
| dcterms.dateSubmitted | 2017-09-26T17:10:15Z | |
| dcterms.description | Department of Molecular and Cellular Biology. | en_US |
| dcterms.extent | 200 pg. | en_US |
| dcterms.format | Monograph | |
| dcterms.format | Application/PDF | en_US |
| dcterms.identifier | Vestin_grad.sunysb_0771E_11630.pdf | en_US |
| dcterms.identifier | http://hdl.handle.net/11401/77828 | |
| dcterms.identifier | 11401/77828/3/CHD5(4timesfast).mov | en_US |
| dcterms.issued | 2013-05-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Submitted by Jason Torre (fjason.torre@stonybrook.edu) on 2017-09-26T17:10:15Z
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| dcterms.provenance | Made available in DSpace on 2017-09-26T17:10:15Z (GMT). No. of bitstreams: 1
Vestin_grad.sunysb_0771E_11630.pdf: 9125483 bytes, checksum: 1df63baf1d7f3e818835c40335a4be57 (MD5)
Previous issue date: 2013-05-01 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Chromatin, Dendrite, Differentiation, Hyperactive, Neuron | |
| dcterms.subject | Cellular biology | |
| dcterms.title | The chromatin remodeler Chd5 regulates dendritic architecture and behavior | |
| dcterms.type | Dissertation | |
