Deng Jiamin, Wang Shangqi, Li Nan, Chen Xiaoyan, Wang Biying, Liu Han, Zhu Lei, Cong Wei, Xiao Jing, Liu Chao
Department of Oral Pathology, School of Stomatology, Dalian Medical University, Dalian, China.
Dalian Key Laboratory of Basic Research in Oral Medicine, School of Stomatology, Dalian Medical University, Dalian, China.
Front Cell Dev Biol. 2021 Sep 7;9:711334. doi: 10.3389/fcell.2021.711334. eCollection 2021.
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 transgene via 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 , 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 soft palates were suggested to result from the repressed 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, (), and expression in 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 and the soft palates, the hypoplastic or abrogated muscles affected little the fusion of soft palate. Although the , , and transcription was significantly repressed in the tenogenic mesenchyme of the soft palate, the Sox9 expression, and the and 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.
骨形态发生蛋白（BMP）信号通路在硬腭发育过程中对腭发生的作用已有充分记载；然而，关于BMP信号通路如何调节软腭发育却知之甚少。在本研究中，我们通过等位基因过表达转基因以抑制发育中的软腭中的BMP信号通路。我们发现BMP-Smad信号通路在腭部肌肉和周围间充质中被检测到。当BMP-Smad信号通路被过表达抑制时，软腭架尺寸减小，伴有肌肉发育不全和外翻性低磷酸酯酶症（HPP）。软腭中细胞增殖和存活的下调被认为是由于转录和Gli1活性受到抑制，这意味着BMP-Shh-Gli1网络在软腭发育中与在硬腭发育中发挥了类似作用。软腭中Sox9、（）和表达的下调表明腱膜和肌腱的分化受损，这被认为导致了腭部肌肉发育不全。有趣的是，在和软腭中，发育不全或缺失的肌肉对软腭融合影响很小。尽管在软腭的成腱间充质中、和转录显著受到抑制，但腱膜间充质中的Sox9表达以及和转录几乎未受影响。这表明软腭融合受腭帆张肌（TVP）和腭帆提肌（LVP）水平的间充质线索控制，但受腭咽肌（PLP）水平的肌源性成分控制。
