Essential role of <i>Msx1</i> in regulating anterior-posterior patterning of the secondary palate in mice

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

doi:10.1016/j.jgg.2021.07.006

Volume 49 Issue 1

Jan. 2022

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Article Navigation > Journal of Genetics and Genomics > 2022 > 49(1): 63-73

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

doi: 10.1016/j.jgg.2021.07.006

a Institute of Life Sciences, College of Life and Environmental Sciences, Key Laboratory of Mammalian Organogenesis and Regeneration, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China;
b The Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang 310015, China

Funds:

We thank Ryan Chastain-Gross and Michal Bell, Ph.D, from Liwen Bianji, Edanz Group China, for editing the English text of a draft of this manuscript. This work was supported by grants from the National Natural Scientific Foundation of China (81771028 and 317771593), Medical Health Science and Technology Project of Zhejiang (2021KY891) and Medical Health Science and Technology Major Project of Hangzhou (Z20200046).

Received Date: 2021-04-07
Revised Date: 2021-06-24
Accepted Date: 2021-07-07
Publish Date: 2021-07-31

Abstract

Abstract

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 (RosaMsx1) 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 RosaMsx1 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 medial-posterior 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.
- Cleft palate,
- Conditional knock-in,
- Mouse model,
- Msx1,
- Organ development

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References(41)

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