Noggin Overexpression Impairs the Development of Muscles, Tendons, and Aponeurosis in Soft Palates by Disrupting BMP-Smad and Shh-Gli1 Signaling.
Noggin Overexpression Impairs the Development of Muscles, Tendons, and Aponeurosis in Soft Palates by Disrupting BMP-Smad and Shh-Gli1 Signaling.
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Noggin 过度表达通过破坏 BMP-Smad 和 Shh-Gli1 信号传导损害软腭肌肉、肌腱和腱膜的发育
DOI：
10.3389/fcell.2021.711334
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发表时间：
2021
影响因子：
5.5
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Deng J;Wang S;Li N;Chen X;Wang B;Liu H;Zhu L;Cong W;Xiao J;Liu C
骨形态发生蛋白（BMP）信号在硬腭发育中的作用已有很好的研究，但关于BMP信号如何调控软腭发育的研究却知之甚少。在这项研究中，我们通过Osr 2-creKI等位基因过表达Noggin转基因来抑制发育中的软腭中的BMP信号传导。我们发现BMP-Smad信号在腭肌和周围间充质中被检测到。当BMP-Smad信号被过表达的Noggin抑制时，软腭架的尺寸减小，肌肉发育不良和外向性磷酸酶过少症（HPP）。Osr 2-creKI;pMes-Noggin软腭中下调的细胞增殖和存活被认为是由Shh转录和Gli 1活性受抑制引起的，暗示BMP-Shh-Gli 1网络在软腭发育中起着与硬腭相似的作用。Osr 2-creKI;pMes-Noggin软腭中Sox 9、Tenascin-C（TnC）和Col 1表达下调表明腱膜和肌腱分化受损，这被认为是导致腭肌发育不良的原因。有趣的是，在Myf 5-creKI;pMes-Noggin和Myf 5-creKI; Rosa 26 R-DTA软腭中，发育不良或废除的肌肉对软腭融合的影响很小。虽然Scx，Tnc，和Co 1转录显着抑制在肌腱间充质的Myf 5-creKI;pMes-Noggin软腭，Sox 9的表达，和Tnc和Col 1转录腱膜间充质几乎不受影响。提示软腭的融合在腭帆张肌（TVP）和腭帆提肌（LVP）水平上受间充质线索的控制，而在腭咽肌（PLP）水平上受肌源性成分的控制。
The roles of bone morphogenetic protein (BMP) signaling in palatogenesis were well documented in the developing hard palate; however, little is known about how BMP signaling regulates the development of soft palate. In this study, we overexpressed Noggin transgene via Osr2-creKI allele to suppress BMP signaling in the developing soft palate. We found that BMP-Smad signaling was detected in the palatal muscles and surrounding mesenchyme. When BMP-Smad signaling was suppressed by the overexpressed Noggin, the soft palatal shelves were reduced in size with the hypoplastic muscles and the extroversive hypophosphatasia (HPP). The downregulated cell proliferation and survival in the Osr2-creKI;pMes-Noggin soft palates were suggested to result from the repressed Shh transcription and Gli1 activity, implicating that the BMP-Shh-Gli1 network played a similar role in soft palate development as in the hard palate. The downregulated Sox9, Tenascin-C (TnC), and Col1 expression in Osr2-creKI;pMes-Noggin soft palate indicated the impaired differentiation of the aponeurosis and tendons, which was suggested to result in the hypoplasia of palatal muscles. Intriguingly, in the Myf5-creKI;pMes-Noggin and the Myf5-creKI;Rosa26R-DTA soft palates, the hypoplastic or abrogated muscles affected little the fusion of soft palate. Although the Scx, Tnc, and Co1 transcription was significantly repressed in the tenogenic mesenchyme of the Myf5-creKI;pMes-Noggin soft palate, the Sox9 expression, and the Tnc and Col1 transcription in aponeurosis mesenchyme were almost unaffected. It implicated that the fusion of soft palate was controlled by the mesenchymal clues at the tensor veli palatini (TVP) and levator veli palatini (LVP) levels, but by the myogenic components at the palatopharyngeus (PLP) level.
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影响因子：
5.5
作者：
Nassari S;Duprez D;Fournier-Thibault C
通讯作者：
Fournier-Thibault C
影响因子：
--
作者：
Friedrichs M;Wirsdöerfer F;Flohé SB;Schneider S;Wuelling M;Vortkamp A
通讯作者：
Vortkamp A
影响因子：
5.6
作者：
Orfei, Carlotta Perucca;Vigano, Marco;de Girolamo, Laura
通讯作者：
de Girolamo, Laura
影响因子：
5.3
作者：
Parada, Carolina;Li, Jingyuan;Chai, Yang
通讯作者：
Chai, Yang
影响因子：
2.7
作者：
Baek JA;Lan Y;Liu H;Maltby KM;Mishina Y;Jiang R
通讯作者：
Jiang R