Zic2 and Zic3 synergistically control neurulation and segmentation of paraxial mesoderm in mouse embryo
Zic2 and Zic3 synergistically control neurulation and segmentation of paraxial mesoderm in mouse embryo
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DOI：
10.1016/j.ydbio.2007.04.003
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发表时间：
2007-06-15
影响因子：
2.7
通讯作者：
Aruga, Jun
中科院分区：
文献类型：
--
作者：
Inoue, Takashi;Ota, Maya;Aruga, Jun
ZIC家族锌指蛋白在动物发育过程中发挥着多种作用。在小鼠中，已有5个ZIC基因(Zic1-5)被报道。尽管这些基因的表达谱部分重叠，但每个Zic的小鼠突变体都表现出不同的表型。为了揭示可能的多余角色，我们对Zic2/Zic3复合突变小鼠进行了表征。Zic2和Zic3均表达于卵裂期前的中胚层，形成的体节和新生成的体节具有不同的时空加重。Zic2等位基因杂合子和Zic3基因缺失的小鼠通常表现出严重的轴骨畸形，包括不对称或嘴-尾桥椎体，尾部椎骨数量减少，这在单个突变体中并不明显。在这些缺陷之前，体细胞标志物的表达受到干扰，原始条纹中的近轴中胚层祖细胞减少。这些结果表明，Zic2和Zic3在多个阶段共同控制着旁中胚层的分割。除了节段异常外，复合突变体还显示出贯穿整个吻尾范围的神经管缺陷(颅裂)，这表明神经形成是Zic2和Zic3具有冗余功能的另一种发育过程。(C)2007 Elsevier Inc.保留所有权利。
Zic family zinc-finger proteins play various roles in animal development. in mice, five Zic genes (Zic1-5) have been reported. Despite the partly overlapping expression profiles of these genes, mouse mutants for each Zic show distinct phenotypes. To uncover possible redundant roles, we characterized Zic2/Zic3 compound mutant mice. Zic2 and Zic3 are both expressed in presomitic mesoderm, forming and newly generated somites with differential spatiotemporal accentuation. Mice heterozygous for the hypomorphic Zic2 allele together with null Zic3 allele generally showed severe malformations of the axial skeleton, including asymmetric or rostro-caudally bridged vertebrae, and reduction of the number of caudal vertebral bones, that are not obvious in single mutants. These defects were preceded by perturbed somitic marker expression, and reduced paraxial mesoderm progenitors in the primitive streak. These results suggest that Zic2 and Zic3 cooperatively control the segmentation of paraxial mesoderm at multiple stages. In addition to the segmentation abnormality, the compound mutant also showed neural tube defects that ran the entire rostro-caudal extent (craniorachischisis), suggesting that neurulation is another developmental process where Zic2 and Zic3 have redundant functions. (C) 2007 Elsevier Inc. All rights reserved.