Embryonic expression profile of chicken chd7, the ortholog of the causative gene for CHARGE syndrome
Embryonic expression profile of chicken chd7, the ortholog of the causative gene for CHARGE syndrome
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DOI：
10.1002/bdra.20330
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发表时间：
2007-01-01
影响因子：
--
通讯作者：
Kosaki, Kenjiro
中科院分区：
文献类型：
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作者：
Aramaki, Michihiko;Kimura, Tokuhiro;Kosaki, Kenjiro
背景：CHARGE综合征代表一系列畸形：C，虹膜或视网膜的结肠瘤；H、心脏缺陷；A， choanae闭锁；R，生长和/或发育迟缓；G，生殖器异常；E，耳朵异常。最近，染色体8q12.1上的染色体结构域解旋酶dna结合蛋白-7 （CHD7）被确定为CHARGE综合征的致病基因。由于CHD7是通过定位克隆方法被鉴定为致病基因，因此CHD7在早期胚胎发生中的作用有待进一步研究。方法：将受精卵孵育至汉堡期和汉密尔顿期4 ~ 20期，采用全株原位杂交技术进行研究。利用鸡EST序列数据库，鉴定出鸡CHD7 （cChd7）序列对应的鸡EST克隆。从EST克隆中合成地高辛标记的RNA探针，并将其原位杂交到胚胎标本上。结果：cChd7在8-20期呈泛神经元表达。它在整个吻侧神经外胚层和沿吻侧尾轴表达，但在更外侧的非神经元外胚层中不表达。在神经管附近，在视神经基和耳神经基上检测到cChd7转录本。在第20期，cChd7在鳃弓和嗅觉基板以及脑和视、耳基板中表达。结论：cChd7在人CHARGE综合征患者的神经上皮、耳基、视基、鳃弓和嗅基中表达，这些组织是影响器官的原始组织。
BACKGROUND: CHARGE syndrome represents a constellation of malformations: C, coloboma of the iris or retina; H, heart defects; A, atresia of the choanae; R, retardation of growth and/or development; G, genital anomalies; and E, ear abnormalities. Recently, the Chromodomain helicase DNA-binding protein-7 (CHD7) at chromosome 8q12.1 was identified as a causative gene for CHARGE syndrome. Because CHD7 was identified as a causative gene using a positional cloning approach, the role of CHD7 in early embryogenesis needs to be further investigated. METHODS: Fertilized chick eggs were incubated to Hamburger and Hamilton stages 4-20 and were studied using whole mount in situ hybridization. Chicken EST clones corresponding to the chicken CHD7 (cChd7) sequence were identified using the chicken EST sequence database. From the EST clones, a digoxigenin-labeled RNA probe was synthesized and hybridized in situ to the embryonic specimens. RESULTS: The expression of cChd7 was pan-neuronal at stages 8-20. It was expressed throughout the rostral neural ectoderm and along the rostrocaudal axis but was absent from the more lateral, non-neuronal ectoderm. Adjacent to the neural tube, cChd7 transcripts were detected at the optic and otic placodes. At stage 20, cChd7 expression was observed in the branchial arches and olfactory placodes in addition to brain and optic and otic placodes. CONCLUSIONS: cChd7 was expressed in the neural epithelium, the otic placodes, the optic placodes, the branchial arches, and the olfactory placodes, which are the primordial tissues that give rise to organs affected in human CHARGE syndrome patients.