Chromatin remodeler Chd7 regulates photoreceptor development and outer segment length.
Chromatin remodeler Chd7 regulates photoreceptor development and outer segment length.
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DOI：
10.1016/j.exer.2022.109299
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发表时间：
2023-01
影响因子：
3.4
通讯作者：
Morris, Ann C.
中科院分区：
文献类型：
--
作者：
Krueger, Laura A.;Bills, Jessica D.;Lim, Zun Yi;Skidmore, Jennifer M.;Martin, Donna M.;Morris, Ann C.
染色质重塑因子CHD7的突变是CHARGE综合征的主要原因，CHARGE综合征是一种先天性疾病，通常包括眼部缺损。虽然已知CHD7是适当的眼部形态发生所需的，但其在视网膜发育中的作用尚未得到彻底研究。鉴于CHARGE综合征患者即使没有缺损也会出现视力障碍，因此需要更好地了解CHD7在视网膜中的功能。在这项研究中，我们的特点是在发育中的斑马鱼和小鼠视网膜的Chd7的表达模式和记录的Chd7功能丧失突变体的眼和视网膜表型。斑马鱼Chd7表达在整个视网膜神经上皮细胞时，视网膜祖细胞积极增殖，后来在新的有丝分裂后视网膜细胞的子集。在视网膜发育的阶段，当大多数视网膜细胞类型的终末分化，Chd7的表达仍然很强的神经节细胞层和内核层的一些细胞。有趣的是，在外核层中也观察到Chd7的强表达，其中Chd7与有丝分裂后的视锥和视杆光感受器的标记物共表达。小鼠CHD7的表达显示出类似的模式，包括在神经节细胞、内核层细胞的亚群中的表达，以及迟至P15在远端外核层中的表达。两种不同的突变chd7斑马鱼系的特点是眼睛和视网膜缺陷。这些突变体表现出小眼症、视锥光感受器数量减少以及视杆和视锥光感受器外节截短。在杂合子Chd7突变小鼠中也观察到锥体光感受器数目减少和外节异常。总之，我们在斑马鱼和小鼠中的结果揭示了Chd7在视网膜发育和感光器外段形态发生中的保守的、先前未描述的作用。此外，我们的工作提出了一个途径，未来调查的发病机制，视觉系统缺陷的CHARGE综合征。
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.
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影响因子：
2.7
作者：
Forbes-Osborne MA;Wilson SG;Morris AC
通讯作者：
Morris AC
影响因子：
3.5
作者：
Bryan, John M.;Fufa, Temesgen D.;McGaughey, David M.
通讯作者：
McGaughey, David M.
DOI：
10.1016/j.bbagrm.2015.06.006
发表时间：
2015-08-01
影响因子：
4.7
作者：
Bishop, Brett;Ho, Kwok Ki;Ogas, Joe
通讯作者：
Ogas, Joe
影响因子：
5.1
作者：
HALL, BD
通讯作者：
HALL, BD
影响因子：
4.5
作者：
Garnai, Sarah J.;Brinkmeier, Michelle L.;Prasovid, Lev
通讯作者：
Prasovid, Lev