The role of Zic genes in inner ear development in the mouse: Exploring mutant mouse phenotypes.
The role of Zic genes in inner ear development in the mouse: Exploring mutant mouse phenotypes.
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DOI：
10.1002/dvdy.24186
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Barald KF
中科院分区：
文献类型：
--
作者：
Chervenak AP;Bank LM;Thomsen N;Glanville-Jones HC;Jonathan S;Millen KJ;Arkell RM;Barald KF
小鼠Zic基因(Zic1-5)表达于背侧后脑和邻近发育的内耳的骨膜间充质(POM)。ZIC基因参与了包括耳朵在内的许多器官系统的发育信号通路，尽管它们的确切作用尚未完全阐明。本研究探讨了Zic1、Zic2和Zic4基因在小鼠内耳发育过程中的作用，发现Zic1/Zic4双突变体在内耳形态上没有明显的缺陷。相比之下，Zic2kd/kd和Zic2Ku/Ku突变体的内耳在内淋巴管/囊和半规管形成以及内耳的耳蜗延伸方面存在严重但不同程度的形态缺陷。通过原位杂交分析Zic2Ku/Ku突变体的耳囊模式，发现Gbx2和Pax2的表达模式发生了变化。这些实验提供了第一个遗传学证据，证明Zic基因是内耳形态发生所必需的。ZIC2功能丧失并不能阻止最初的耳囊形成，但会导致分子异常，伴随着内淋巴管的形态发生。功能性听力障碍经常伴随着内耳畸形，这使得Zic2成为正在进行的识别人类听力损失遗传基础的新的候选基因。
Murine Zic genes (Zic1-5) are expressed in the dorsal hindbrain and in periotic mesenchyme (POM) adjacent to the developing inner ear. Zic genes are involved in developmental signaling pathways in many organ systems, including the ear, although their exact roles haven't been fully elucidated. This report examines the role of Zic1, Zic2, and Zic4 during inner ear development in mouse mutants in which these Zic genes are affected Zic1/Zic4 double mutants don't exhibit any apparent defects in inner ear morphology. By contrast, inner ears from Zic2kd/kd and Zic2Ku/Ku mutants have severe but variable morphological defects in endolymphatic duct/sac and semicircular canal formation and in cochlear extension in the inner ear. Analysis of otocyst patterning in the Zic2Ku/Ku mutants by in situ hybridization showed changes in the expression patterns of Gbx2 and Pax2. The experiments provide the first genetic evidence that the Zic genes are required for morphogenesis of the inner ear. Zic2 loss-of-function doesn't prevent initial otocyst patterning but leads to molecular abnormalities concomitant with morphogenesis of the endolymphatic duct. Functional hearing deficits often accompany inner ear dysmorphologies, making Zic2 a novel candidate gene for ongoing efforts to identify the genetic basis of human hearing loss.
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影响因子：
4.6
作者：
Ebert, PJ;Timmer, JR;Johnson, JE
通讯作者：
Johnson, JE
DOI：
10.1023/a:1007057719025
发表时间：
1999-10-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
Hutson, MR;Lewis, JE;Barald, KF
通讯作者：
Barald, KF
影响因子：
4.6
作者：
Blank, Marissa C.;Grinberg, Inessa;Millen, Kathleen J.
通讯作者：
Millen, Kathleen J.
影响因子：
30.8
作者：
Brown, SA;Warburton, D;Muenke, M
通讯作者：
Muenke, M
影响因子：
2.7
作者：
Elms, P;Siggers, P;Arkell, R
通讯作者：
Arkell, R