Mouse Zic5 deficiency results in neural tube defects and hypoplasia of cephalic neural crest derivatives
Mouse Zic5 deficiency results in neural tube defects and hypoplasia of cephalic neural crest derivatives
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DOI：
10.1016/j.ydbio.2004.02.017
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发表时间：
2004-06-01
影响因子：
2.7
通讯作者：
Mikoshiba, K
中科院分区：
文献类型：
--
作者：
Inoue, T;Hatayama, M;Mikoshiba, K
Zic家族基因编码锌指蛋白，是果蝇配对规则基因odd-paired的同源基因。在本研究中，我们鉴定了小鼠Zic家族基因的第五个成员，小鼠Zic5。Zic5位于Zic2附近，Zic2是导致人脑畸形综合征（holoproencephaly， HPE）的基因。在胚胎期，Zic5在神经组织背侧和肢体表达。Zic5与其他Zic基因表达重叠，与Zic2表达最接近，但不完全相同。靶向破坏Zic5导致吻端神经管关闭不足，与Zic2突变小鼠相似。此外，zic5缺陷小鼠表现出神经嵴衍生的面部骨骼畸形，特别是下颌骨，这在其他Zic家族突变体中未被观察到。在胚胎期，第一鳃弓发育迟缓，三叉神经和面神经伸展迟缓。神经嵴标记染色显示突变胚胎头背区神经嵴细胞较少，但其迁移无明显变化。当小鼠Zic5在爪蟾胚胎中过表达时，神经嵴标记的表达增强。这些发现提示Zic5参与了小鼠发育过程中神经嵴组织的生成。ZIC5在人类中也位于ZIC2附近，ZIC2所在的13q32缺失会导致先天性脑和手指畸形，称为“13q32缺失综合征”。基于它们在小鼠胚胎中的相似表达模式和在ZIC5缺陷突变小鼠中观察到的畸形，人类ZIC5可能参与了缺失综合征。(C) 2004爱思唯尔公司版权所有。
Zic family genes encode zinc finger proteins, which are homologues of the Drosophila pair-rule gene odd-paired. In the present study, we characterized the fifth member of the mouse Zic family gene, mouse Zic5. Zic5 is located near Zic2, which is responsible for human brain malformation syndrome (holoprosencephaly, or HPE). In embryonic stages, Zic5 was expressed in dorsal part of neural tissues and limbs. Expression of Zic5 overlapped with those of other Zic genes, most closely with Zic2, but was not identical. Targeted disruption of Zic5 resulted in insufficient neural tube closure at the rostral end, similar to that seen in Zic2 mutant mice. In addition, the Zic5-deficient mice exhibited malformation of neural-crest-derived facial bones, especially the mandible, which had not been observed in other Zic family mutants. During the embryonic stages, there were delays in the development of the first branchial arch and extension of the trigeminal and facial nerves. Neural crest marker staining revealed fewer neural crest cells in the dorsal cephalic region of the mutant embryos without significant changes in their migration. When mouse Zic5 was overexpressed in Xenopus embryos, expression of a neural crest marker was enhanced. These findings suggested that Zic5 is involved in the generation of neural crest tissue in mouse development. ZIC5 is also located close to ZIC2 in humans, and deletions of 13q32, where ZIC2 is located, lead to congenital brain and digit malformations known as the "13q32 deletion syndrome". Based on both their similar expression pattern in mouse embryos and the malformations observed in Zic5-deficient mutant mice, human ZIC5 might be involved in the deletion syndrome. (C) 2004 Elsevier Inc. All rights reserved.