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Versatile Roles of the Chromatin Remodeler CHD7 during Brain Development and Disease.

ABSTRACT: CHD7 (Chromo-Helicase-DNA binding protein 7) protein is an ATP-dependent chromatin remodeler. Heterozygous mutation of the CHD7 gene causes a severe congenital disease known as CHARGE syndrome. Most CHARGE syndrome patients have brain structural anomalies, implicating an important role of CHD7 during brain development. In this review, we summarize studies dissecting developmental functions of CHD7 in the brain and discuss pathogenic mechanisms behind neurodevelopmental defects caused by mutation of CHD7. As we discussed, CHD7 protein exhibits a remarkably specific and dynamic expression pattern in the brain. Studies in human and animal models have revealed that CHD7 is involved in multiple developmental lineages and processes in the brain. Mechanistically, CHD7 is essential for neural differentiation due to its transcriptional regulation in progenitor cells.

SUBMITTER: Feng W

PROVIDER: S-EPMC5625114 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Versatile Roles of the Chromatin Remodeler CHD7 during Brain Development and Disease.

Feng Weijun W Shao Chunxuan C Liu Hai-Kun HK

Frontiers in molecular neuroscience 20170928

CHD7 (Chromo-Helicase-DNA binding protein 7) protein is an ATP-dependent chromatin remodeler. Heterozygous mutation of the <i>CHD7</i> gene causes a severe congenital disease known as CHARGE syndrome. Most CHARGE syndrome patients have brain structural anomalies, implicating an important role of CHD7 during brain development. In this review, we summarize studies dissecting developmental functions of CHD7 in the brain and discuss pathogenic mechanisms behind neurodevelopmental defects caused by m ...[more]

PMID: 29033785

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Project description:Mutations in the chromatin remodeling factor CHD7 are the predominant cause of CHARGE syndrome, a congenital disorder that frequently includes ocular coloboma. Although CHD7 is known to be required for proper ocular morphogenesis, its role in retinal development has not been thoroughly investigated. Given that individuals with CHARGE syndrome can experience visual impairment even in the absence of coloboma, a better understanding of CHD7 function in the retina is needed. In this study, we characterized the expression pattern of Chd7 in the developing zebrafish and mouse retina and documented ocular and retinal phenotypes in Chd7 loss-of-function mutants. Zebrafish Chd7 was expressed throughout the retinal neuroepithelium when retinal progenitor cells were actively proliferating, and later in subsets of newly post-mitotic retinal cells. At stages of retinal development when most retinal cell types had terminally differentiated, Chd7 expression remained strong in the ganglion cell layer and in some cells in the inner nuclear layer. Intriguingly, strong expression of Chd7 was also observed in the outer nuclear layer where it was co-expressed with markers of post-mitotic cone and rod photoreceptors. Expression of mouse CHD7 displayed a similar pattern, including expression in the ganglion cells, subsets of inner nuclear layer cells, and in the distal outer nuclear layer as late as P15. Two different mutant chd7 zebrafish lines were characterized for ocular and retinal defects. These mutants displayed microphthalmia, reduced numbers of cone photoreceptors, and truncated rod and cone photoreceptor outer segments. Reduced cone photoreceptor number and abnormal outer segments were also observed in heterozygous Chd7 mutant mice. Taken together, our results in zebrafish and mouse reveal a conserved, previously undescribed role for Chd7 in retinal development and photoreceptor outer segment morphogenesis. Moreover, our work suggests an avenue of future investigation into the pathogenesis of visual system defects in CHARGE syndrome.

Dataset Information

Versatile Roles of the Chromatin Remodeler CHD7 during Brain Development and Disease.

Publications

Versatile Roles of the Chromatin Remodeler CHD7 during Brain Development and Disease.

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