Noggin Overexpression Impairs the Development of Muscles, Tendons, and Aponeurosis in Soft Palates by Disrupting BMP-Smad and Shh-Gli1 Signaling.

Lei Zhu,Jiamin Deng,Shangqi Wang,Biying Wang,Xiaoyan Chen,Nan Li,Chao Liu,Han Liu,Wei Cong,Jing Xiao

doi:10.3389/fcell.2021.711334

Lei Zhu, Jiamin Deng + Show 8 more

Open Access

https://doi.org/10.3389/fcell.2021.711334

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Abstract

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.

Highlights

The secondary palate of mammals is composed of the hard palate occupying the anterior two-thirds of the entire palate and the soft palates in the posterior one-third of palate (Bush and Jiang, 2012)
Our study suggested that bone morphogenetic protein (BMP)-Smad signaling was activated in the HPP and the mesenchyme surrounding tensor veli palatini (TVP), levator veli palatini (LVP), superior pharyngeal constrictors (SPCs), and PLP
The overexpressed Noggin by Osr2-creKI suppressed the BMP-Smad signaling severely in the mesenchyme surrounding palatal muscles, but mildly in the HPP. These results suggested that similar to Wnt/β-catenin, FGF, and Hh signaling, the BMP-Smad signaling in the palatal mesenchyme played a role in the myogenesis of soft palates (Janecková et al, 2019)

Summary

Introduction

The secondary palate of mammals is composed of the hard palate occupying the anterior two-thirds of the entire palate and the soft palates in the posterior one-third of palate (Bush and Jiang, 2012). The developing hard palate is constituted by the covering epithelium that originated from surface ectoderm and the mesenchyme derived from cranial neural crest (Bush and Jiang, 2012; Li et al, 2017). The soft palate contains the covering epithelium and neural crest-derived mesenchyme differentiating into tendons and other irregular connective tissues (Nassari et al, 2017), and the myoblasts that originated from the mesoderm-derived branchiomeric mesenchyme (Li et al, 2019). The other four pairs of muscles attach to the palatine aponeurosis, a fan-like fibrous structure connecting the posterior board of the hard palate (Grimaldi et al, 2015; Li et al, 2019). Despite the absence of musculus uvulae, the anatomy of soft palate in mouse is similar to that in humans (Grimaldi et al, 2015; Li et al, 2019)

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