COUP-TFII is required for morphogenesis of the neural crest-derived tympanic ring.
COUP-TFII is required for morphogenesis of the neural crest-derived tympanic ring.
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DOI：
10.1038/s41598-017-12665-0
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发表时间：
2017-09-28
影响因子：
4.6
通讯作者：
You LR
中科院分区：
文献类型：
--
作者：
Hsu WH;Chen CM;You LR
鸡卵白蛋白上游启动子转录因子II （COUP-TFII）在细胞生长、细胞分化和细胞命运决定中起着关键作用。尽管全基因组研究已经确定了COUP-TFII与主要参与神经嵴细胞（NCC）发育和颅面形态发生的基因集结合，但在体内，COUP-TFII与NCC之间的直接功能联系尚未得到很好的表征。在这项研究中，我们发现COUP-TFII在ncc及其衍生物亚群中表达，并且在小鼠ncc中靶向消融COUP-TFII会导致鼓室环明显缩短和分叉，从而干扰外声道内陷的尾侧方向。然而，Wnt1-Cre/+中锤骨柄（MM）的形成；COUP-TFII flox/flox小鼠没有受到干扰，这表明鼓室环的吻侧部分足以支持MM的正常发育。有趣的是，我们发现COUP-TFII的缺失上调了鼓环原基中的Sox9，并影响了间充质凝结前成骨前细胞的分布。总之，我们的研究结果表明，COUP-TFII在调节ncc衍生的鼓室环的模式中起着至关重要的作用。
Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII) plays pivotal roles in cell growth, cell differentiation, and cell fate determination. Although genome-wide studies have identified COUP-TFII binding on gene sets mainly involved in neural crest cell (NCC) development and craniofacial morphogenesis, the direct functional connection between COUP-TFII and NCCs in vivo has not been well characterized. In this study, we show that COUP-TFII is expressed in the subpopulation of NCCs and its derivatives, and targeted ablation of COUP-TFII in mouse NCCs results in markedly shortened and bifurcated tympanic rings, which in turn disturb the caudal direction of external acoustic meatus invagination. However, formation of the manubrium of the malleus (MM) in Wnt1-Cre/+;COUP-TFII flox/flox mice is not perturbed, suggesting that the rostral half of the tympanic ring is sufficient to support proper MM development. Interestingly, we found that loss of COUP-TFII up-regulates Sox9 in the tympanic ring primordium and affects the distribution of preosteoblasts before mesenchymal condensation. Together, our results demonstrate that COUP-TFII plays an essential role in regulating the patterning of the NCC-derived tympanic ring.