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腭发生和腭裂中的基因调控网络和信号通路:全面综述。

Gene Regulatory Networks and Signaling Pathways in Palatogenesis and Cleft Palate: A Comprehensive Review.

机构信息

Department of Anatomy, School of Medicine, Kangwon National University, Chuncheon 24341, Republic of Korea.

BIT Medical Convergence Graduate Program, Department of Microbiology and Immunology, School of Medicine, Kangwon National University, Chuncheon 24341, Republic of Korea.

出版信息

Cells. 2023 Jul 27;12(15):1954. doi: 10.3390/cells12151954.


DOI:10.3390/cells12151954
PMID:37566033
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10416829/
Abstract

Palatogenesis is a complex and intricate process involving the formation of the palate through various morphogenetic events highly dependent on the surrounding context. These events comprise outgrowth of palatal shelves from embryonic maxillary prominences, their elevation from a vertical to a horizontal position above the tongue, and their subsequent adhesion and fusion at the midline to separate oral and nasal cavities. Disruptions in any of these processes can result in cleft palate, a common congenital abnormality that significantly affects patient's quality of life, despite surgical intervention. Although many genes involved in palatogenesis have been identified through studies on genetically modified mice and human genetics, the precise roles of these genes and their products in signaling networks that regulate palatogenesis remain elusive. Recent investigations have revealed that palatal shelf growth, patterning, adhesion, and fusion are intricately regulated by numerous transcription factors and signaling pathways, including Sonic hedgehog (Shh), bone morphogenetic protein (Bmp), fibroblast growth factor (Fgf), transforming growth factor beta (Tgf-β), Wnt signaling, and others. These studies have also identified a significant number of genes that are essential for palate development. Integrated information from these studies offers novel insights into gene regulatory networks and dynamic cellular processes underlying palatal shelf elevation, contact, and fusion, deepening our understanding of palatogenesis, and facilitating the development of more efficacious treatments for cleft palate.

摘要

腭发生是一个复杂而精细的过程,涉及通过高度依赖周围环境的各种形态发生事件形成腭。这些事件包括胚胎上颌隆起的腭突向外生长,从垂直位置抬高到舌上方的水平位置,以及随后在中线处粘附和融合,将口腔和鼻腔分开。这些过程中的任何干扰都可能导致腭裂,这是一种常见的先天性异常,尽管进行了手术干预,但仍会显著影响患者的生活质量。尽管通过对基因修饰小鼠和人类遗传学的研究已经确定了许多参与腭发生的基因,但这些基因及其产物在调节腭发生的信号网络中的精确作用仍然难以捉摸。最近的研究表明,腭突的生长、模式形成、粘附和融合受到许多转录因子和信号通路的精细调节,包括 Sonic hedgehog (Shh)、骨形态发生蛋白 (Bmp)、成纤维细胞生长因子 (Fgf)、转化生长因子 β (Tgf-β)、Wnt 信号通路等。这些研究还确定了许多对腭发育至关重要的基因。这些研究的综合信息提供了对基因调控网络和腭突抬高、接触和融合背后的动态细胞过程的新见解,加深了我们对腭发生的理解,并促进了更有效的腭裂治疗方法的开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/988c/10416829/251d001fc989/cells-12-01954-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/988c/10416829/e852d8c3adc3/cells-12-01954-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/988c/10416829/b47c2a6e9cf4/cells-12-01954-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/988c/10416829/251d001fc989/cells-12-01954-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/988c/10416829/e852d8c3adc3/cells-12-01954-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/988c/10416829/b47c2a6e9cf4/cells-12-01954-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/988c/10416829/251d001fc989/cells-12-01954-g002.jpg

相似文献

[1]
Gene Regulatory Networks and Signaling Pathways in Palatogenesis and Cleft Palate: A Comprehensive Review.

Cells. 2023-7-27

[2]
Molecular and Cellular Mechanisms of Palate Development.

J Dent Res. 2017-10

[3]
The Function and Regulatory Network of Pax9 Gene in Palate Development.

J Dent Res. 2018-12-24

[4]
Rescue of cleft palate in Msx1-deficient mice by transgenic Bmp4 reveals a network of BMP and Shh signaling in the regulation of mammalian palatogenesis.

Development. 2002-9

[5]
Modulating Wnt Signaling Rescues Palate Morphogenesis in Pax9 Mutant Mice.

J Dent Res. 2017-10

[6]
Palatogenesis: morphogenetic and molecular mechanisms of secondary palate development.

Development. 2012-1

[7]
A Shh-Foxf-Fgf18-Shh Molecular Circuit Regulating Palate Development.

PLoS Genet. 2016-1-8

[8]
Indirect modulation of Shh signaling by Dlx5 affects the oral-nasal patterning of palate and rescues cleft palate in Msx1-null mice.

Development. 2009-12

[9]
Transforming Growth Factor-Beta and Sonic Hedgehog Signaling in Palatal Epithelium Regulate Tenascin-C Expression in Palatal Mesenchyme During Soft Palate Development.

Front Physiol. 2020-6-4

[10]
Toward pathogenesis of Apert cleft palate: FGF, FGFR, and TGF beta genes are differentially expressed in sequential stages of human palatal shelf fusion.

Cleft Palate Craniofac J. 2002-5

引用本文的文献

[1]
Extract Mitigates Mycophenolate Mofetil-Induced Human Palatal Cell Proliferation Inhibition by Downregulating .

Plants (Basel). 2025-4-7

[2]
Molecular Regulation of Palatogenesis and Clefting: An Integrative Analysis of Genetic, Epigenetic Networks, and Environmental Interactions.

Int J Mol Sci. 2025-2-6

[3]
PRMT1-methylated MSX1 phase separates to control palate development.

Nat Commun. 2025-1-22

[4]
[Gene-gene/gene-environment interaction of transforming growth factor-β signaling pathway and the risk of non-syndromic oral clefts].

Beijing Da Xue Xue Bao Yi Xue Ban. 2024-6-18

[5]
Exosomes Derived from Human Palatal Mesenchymal Cells Mediate Intercellular Communication During Palatal Fusion by Promoting Oral Epithelial Cell Migration.

Int J Nanomedicine. 2024

[6]
Transforming growth factor beta signaling and craniofacial development: modeling human diseases in zebrafish.

Front Cell Dev Biol. 2024-2-7

[7]
Genetic Inheritance Models of Non-Syndromic Cleft Lip with or without Palate: From Monogenic to Polygenic.

Genes (Basel). 2023-9-24

本文引用的文献

[1]
Mouse models in palate development and orofacial cleft research: Understanding the crucial role and regulation of epithelial integrity in facial and palate morphogenesis.

Curr Top Dev Biol. 2022

[2]
Revisiting the embryogenesis of lip and palate development.

Oral Dis. 2022-7

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Mutat Res Rev Mutat Res. 2021

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Pax9's dual roles in modulating Wnt signaling during murine palatogenesis.

Dev Dyn. 2020-10

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Activation of sonic hedgehog signaling by a Smoothened agonist restores congenital defects in mouse models of endocrine-cerebro-osteodysplasia syndrome.

EBioMedicine. 2019-10-26

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J Dent Res. 2019-5-31

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The molecular anatomy of mammalian upper lip and primary palate fusion at single cell resolution.

Development. 2019-6-17

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Inhibition of the Zeb family prevents murine palatogenesis through regulation of apoptosis and the cell cycle.

Biochem Biophys Res Commun. 2018-10-19

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Small-molecule Wnt agonists correct cleft palates in mutant mice .

Development. 2017-10-15

[10]
Anti-EDAR Agonist Antibody Therapy Resolves Palate Defects in Pax9 Mice.

J Dent Res. 2017-10

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