Zic2 is required for neural crest formation and hindbrain patterning during mouse development

Zic2 is required for neural crest formation and hindbrain patterning during mouse development
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DOI:
10.1016/j.ydbio.2003.09.005
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发表时间:
2003-12-15
影响因子:
2.7
通讯作者:
Arkell, R
Arkell, R
中科院分区:
生物学3区
文献类型:
--
作者:
Elms, P;Siggers, P;Arkell, R

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Zic基因是果蝇配对规则基因奇配对的脊椎动物同源物。Zic基因在神经发育过程中起着多种作用,包括神经板的中外侧分割、神经嵴的诱导和神经发生的抑制。最初在小鼠神经发育期间,Zic 2在整个神经板中表达,而后来在神经外胚层中的表达变得限于神经板的外侧区域。Zic 2的亚型等位基因已经证明,在小鼠中,Zic 2是神经胚形成的时间所需的。我们已经分离出Zic 2的一个新的等位基因,其表现为功能缺失等位基因。对该突变体的分析揭示了Zic 2在早期神经发育过程中的两个进一步功能。Zic 2的突变导致神经嵴产生的延迟和产生的神经嵴细胞数量的减少。这些缺陷是独立的mediolateral分割的neurectoderm和背侧neurectoderm增殖,这两个通常发生在突变体胚胎。此外,Zic2在后脑模式化期间是菱形3和5的正常发育所必需的。这项工作提供了第一个遗传学证据,证明Zic基因参与神经嵴的产生,并首次证明Zic 2在后脑模式中发挥作用。(C)2003年爱思唯尔公司All rights reserved.
The Zic genes are the vertebrate homologues of the Drosophila pair rule gene odd-paired. It has been proposed that Zic genes play several roles during neural development including mediolateral segmentation of the neural plate, neural crest induction, and inhibition of neurogenesis. Initially during mouse neural development Zic2 is expressed throughout the neural plate while later on expression in the neurectoderm becomes restricted to the lateral region of the neural plate. A hypomorphic allele of Zic2 has demonstrated that in the mouse Zic2 is required for the timing of neurulation. We have isolated a new allele of Zic2 that behaves as a loss of function allele. Analysis of this mutant reveals two further functions for Zic2 during early neural development. Mutation of Zic2 results in a delay of neural crest production and a decrease in the number of neural crest cells that are produced. These defects are independent of mediolateral segmentation of the neurectoderm and of dorsal neurectoderm proliferation, both of which occur normally in the mutant embryos. Additionally Zic2 is required during hindbrain patterning for the normal development of rhombomeres 3 and 5. This work provides the first genetic evidence that the Zic genes are involved in neural crest production and the first demonstration that Zic2 functions during hindbrain patterning. (C) 2003 Elsevier Inc. All rights reserved.