Cerebellar Vermis and Midbrain Hypoplasia Upon Conditional Deletion of Chd7 from the Embryonic Mid-Hindbrain Region.
Cerebellar Vermis and Midbrain Hypoplasia Upon Conditional Deletion of Chd7 from the Embryonic Mid-Hindbrain Region.
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DOI：
10.3389/fnana.2017.00086
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发表时间：
2017
影响因子：
2.9
通讯作者：
Basson MA
中科院分区：
文献类型：
--
作者：
Donovan APA;Yu T;Ellegood J;Riegman KLH;de Geus C;van Ravenswaaij-Arts C;Fernandes C;Lerch JP;Basson MA
在早期胚胎发育过程中，来自中脑或峡部组织者（IsO）的成纤维细胞生长因子（FGF）信号减少导致中脑和小脑蚓部发育不全。我们先前报道了Chd 7杂合子胚胎中后脑区域Fgf 8表达和FGF信号传导减少的证据，Chd 7基因在CHARGE（缺损、心脏缺陷、后鼻孔闭锁、生长发育迟缓、泌尿生殖系统异常和耳缺陷）综合征中突变。然而，Chd 7 +/−动物仅表现出轻度小脑蚓部异常。由于Chd 7的纯合缺失是胚胎致死性的，我们从早期胚胎中后脑区域有条件地缺失Chd 7以鉴定CHD 7在中后脑发育中的功能。使用高分辨率结构MRI和组织学相结合，我们报告显着的中脑和小脑蚓部发育不全的纯合子条件突变体。我们发现小脑蚓部发育不全与胚胎FGF 8表达减少和菱形区1（r1）顶板扩大有关。这些发现确定了Chd 7通过Fgf 8调节中后脑发育的重要作用。
Reduced fibroblast growth factor (FGF) signaling from the mid-hindbrain or isthmus organizer (IsO) during early embryonic development results in hypoplasia of the midbrain and cerebellar vermis. We previously reported evidence for reduced Fgf8 expression and FGF signaling in the mid-hindbrain region of embryos heterozygous for Chd7, the gene mutated in CHARGE (Coloboma, Heart defects, choanal Atresia, Retarded growth and development, Genitourinary anomalies and Ear defects) syndrome. However, Chd7+/− animals only exhibit mild cerebellar vermis anomalies. As homozygous deletion of Chd7 is embryonic lethal, we conditionally deleted Chd7 from the early embryonic mid-hindbrain region to identify the function of CHD7 in mid-hindbrain development. Using a combination of high resolution structural MRI and histology, we report striking midbrain and cerebellar vermis hypoplasia in the homozygous conditional mutants. We show that cerebellar vermis hypoplasia is associated with reduced embryonic Fgf8 expression and an expanded roof plate in rhombomere 1 (r1). These findings identify an essential role for Chd7 in regulating mid-hindbrain development via Fgf8.
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影响因子：
1.3
作者：
COLLINS, DL;NEELIN, P;EVANS, AC
通讯作者：
EVANS, AC
影响因子：
5.7
作者：
Lerch, Jason P.;Carroll, Jeffrey B.;Henkelman, R. Mark
通讯作者：
Henkelman, R. Mark
影响因子：
4.7
作者：
Steadman, Patrick E.;Ellegood, Jacob;Lerch, Jason P.
通讯作者：
Lerch, Jason P.
影响因子：
4.5
作者：
Schnetz, Michael P.;Handoko, Lusy;Scacheri, Peter C.
通讯作者：
Scacheri, Peter C.
影响因子：
5.7
作者：
Genovese, CR;Lazar, NA;Nichols, T
通讯作者：
Nichols, T