FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation.
FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation.
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DOI：
10.1038/ng.422
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发表时间：
2009-09
期刊：
影响因子：
30.8
通讯作者：
Millen, Kathleen J.
中科院分区：
文献类型：
--
作者：
Aldinger, Kimberly A.;Lehmann, Ordan J.;Hudgins, Louanne;Chizhikov, Victor V.;Bassuk, Alexander G.;Ades, Lesley C.;Krantz, Ian D.;Dobyns, William B.;Millen, Kathleen J.
Dandy-Walker 畸形 (DWM) 是最常见的人类小脑畸形，只有一个特征相关位点。在这里，我们描述了 6p25.3 上的第二个 DWM 连锁位点，表明包含 FOXC1 的缺失或重复与小脑和后颅窝畸形相关，包括小脑蚓部发育不全 (CVH)、大脑延髓池 (MCM) 和 DWM。 Foxc1缺失小鼠由于间充质分泌信号分子的缺失以及随后蚓部中Atoh1表达的缺失而出现菱形唇的胚胎异常。 Foxc1 纯合亚型具有 CVH，伴有内侧融合和叶状缺陷。已知人类 FOXC1 杂合突变会影响眼睛发育，导致一系列青光眼相关异常（Axenfeld-Rieger 综合征，ARS；MIM 编号 601631）。我们报告了带有 FOXC1 突变的人类的第一个大脑成像数据，并表明这些人也患有 CVH。我们得出的结论是，仅 FOXC1 功能的改变就会导致 CVH 并导致 MCM 和 DWM。我们的结果强调了早期胚胎发生过程中后脑中间充质-神经上皮相互作用的先前未被认识的作用。
Dandy-Walker malformation (DWM), the most common human cerebellar malformation, has only one characterized associated locus. Here we characterize a second DWM-linked locus on 6p25.3, showing that deletions or duplications encompassing FOXC1 are associated with cerebellar and posterior fossa malformations including cerebellar vermis hypoplasia (CVH), mega-cisterna magna (MCM) and DWM. Foxc1-null mice have embryonic abnormalities of the rhombic lip due to loss of mesenchyme-secreted signaling molecules with subsequent loss of Atoh1 expression in vermis. Foxc1 homozygous hypomorphs have CVH with medial fusion and foliation defects. Human FOXC1 heterozygous mutations are known to affect eye development, causing a spectrum of glaucoma-associated anomalies (Axenfeld-Rieger syndrome, ARS; MIM no. 601631). We report the first brain imaging data from humans with FOXC1 mutations and show that these individuals also have CVH. We conclude that alteration of FOXC1 function alone causes CVH and contributes to MCM and DWM. Our results highlight a previously unrecognized role for mesenchyme-neuroepithelium interactions in the mid-hindbrain during early embryogenesis.
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影响因子：
64.8
作者：
BenArie, N;Bellen, HJ;Zoghbi, HY
通讯作者：
Zoghbi, HY
DOI：
10.1073/pnas.95.16.9448
发表时间：
1998-08-04
影响因子：
11.1
作者：
Ma, Q;Jones, D;Springer, TA
通讯作者：
Springer, TA
影响因子：
4.6
作者：
Chizhikov, Victor V.;Lindgren, Anne G.;Millen, Kathleen J.
通讯作者：
Millen, Kathleen J.
影响因子：
10.5
作者：
Lee, KJ;Mendelsohn, M;Jessell, TM
通讯作者：
Jessell, TM
影响因子：
2
作者：
Lin, RJ;Cherry, AM;Hudgins, L
通讯作者：
Hudgins, L