Essential role of Msx1 in regulating anterior-posterior patterning of the secondary palate in mice  

作　　者：Shicheng Zhu Hanjing Song Liangjun Zhong Suman Huo Yukun Fang Wanxin Zhao Xueqin Yang Zhong-Min Dai Rui He Mengsheng Qiu Zunyi Zhang Xiao-Jing Zhu 

机构地区：[1]Institute of Life Sciences,College of Life and Environmental Sciences,Key Laboratory of Mammalian Organogenesis and Regeneration,Hangzhou Normal University,Hangzhou,Zhejiang 311121,China [2]The Affiliated Hospital,Hangzhou Normal University,Hangzhou,Zhejiang 310015,China

出　　处：《Journal of Genetics and Genomics》2022年第1期63-73,共11页遗传学报（英文版）

基　　金：supported by grants from the National Natural Scientific Foundation of China (81771028 and 317771593);Medical Health Science and Technology Project of Zhejiang (2021KY891);Medical Health Science and Technology Major Project of Hangzhou (Z20200046)。

摘　　要：Development of the secondary palate displays molecular heterogeneity along the anterior-posterior axis;however, the underlying molecular mechanism remains largely unknown. MSX1 is an anteriorly expressed transcription repressor required for palate development. Here, we investigate the role of Msx1 in regional patterning of the secondary palate. The Wnt1-Cre-mediated expression of Msx1(Rosa Msx1^(Wnt1-Cre))throughout the palatal mesenchyme leads to cleft palate in mice, associated with aberrant cell proliferation and cell death. Osteogenic patterning of the hard palate in Rosa Msx1^(Wnt1-Cre)mice is severely impaired, as revealed by a marked reduction in palatine bone formation and decreased expression of the osteogenic regulator Sp7. Overexpression and knockout of Msx1 in mice show that the transcription repressor promotes the expression of the anterior palate-specific Alx1 but represses the expression of the medialposterior palate genes Barx1, Meox2, and Tbx22. Furthermore, Tbx22 constitutes a direct Msx1 target gene in the secondary palate, suggesting that Msx1 can directly repress the expression of medial-posterior specific genes. Finally, we determine that Sp7 is downstream of Tbx22 in palatal mesenchymal cells,suggesting that a Msx1/Tbx22/Sp7 axis participates in the regulation of palate development. Our findings unveil a novel role for Msx1 in regulating the anterior-posterior growth and patterning of the secondary palate.

关 键 词：Cleft palate Conditional knock-in Mouse model MSX1 Organ development 

分 类 号：R782.22[医药卫生—口腔医学]