In vivo genetic ablation of the periotic mesoderm affects cell proliferation survival and differentiation in the cochlea.
In vivo genetic ablation of the periotic mesoderm affects cell proliferation survival and differentiation in the cochlea.
复制标题
周膜中胚层的体内遗传消融影响耳蜗中的细胞增殖、存活和分化。
DOI：
10.1016/j.ydbio.2007.08.006
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发表时间：
2007
影响因子：
2.7
通讯作者：
Baldini,Antonio
中科院分区：
文献类型：
--
作者：
Xu,Huansheng;Chen,Li;Baldini,Antonio
T-box转录因子Tbx 1是内耳形态发生所必需的。Tbx 1无效突变体有一个小的耳囊，不能生长和重塑，也不能产生前庭和耳蜗装置。在这里，我们表明，Tbx 1表达驱动的细胞示踪确定了一个人口的耳上皮细胞，有助于大多数的耳囊肿。Tbx 1对于这一人群对内耳的贡献至关重要。Tbx 1的消融后，这个细胞群已经建立了自己的耳囊，恢复标志物表达的生殖系突变体中丢失，但导致严重减少有丝分裂活动，细胞自主。此外，定时细胞命运映射表明，Tbx 1的损失开关的Tbx 1依赖性细胞群体的一些成员的命运，从非神经源性的神经源性，与激活的Delta-Notch途径的事件。最后，Tbx 1的组织特异性消融表明，虽然上述表型异常是由于Tbx 1的上皮表达的损失，耳蜗形态发生需要中胚层Tbx 1的表达。我们的结论是，Tbx 1在内耳的主要功能是控制，细胞自主，贡献，大小和命运的一大群耳上皮细胞，和细胞非自主，耳蜗形态发生。
The T-box transcription factor Tbx1 is required for inner ear morphogenesis. Tbx1 null mutants have a small otocyst that fails to grow and remodel and does not give rise to the vestibular and cochlear apparata. Here we show that Tbx1 expression-driven cell tracing identifies a population of otic epithelial cells that contributes to most of the otocyst. Tbx1 is essential for the contribution of this population to the inner ear. Ablation of Tbx1 after this cell population has established itself in the otocyst, restores marker expression lost in germ line mutants, but causes severe reduction in mitotic activity, cell autonomously. Furthermore, timed cell fate mapping demonstrates that loss of Tbx1 switches the fate of some members of the Tbx1-dependent cell population, from non-neurogenic to neurogenic, an event associated with activation of the Delta–Notch pathway. Finally, tissue-specific ablation of Tbx1 demonstrates that, while the abovementioned phenotypic abnormalities are due to loss of epithelial expression of Tbx1, cochlear morphogenesis requires mesodermal Tbx1 expression. We conclude that the main functions of Tbx1 in the inner ear are to control, cell-autonomously, contribution, size and fate of a large population of otic epithelial cells, and, cell non-autonomously, cochlear morphogenesis.