上腭发生的分子调控机制

许晨; 胡雪峰

doi:10.16098/j.issn.0529-1356.2021.02.025

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解剖学报 ›› 2021, Vol. 52 ›› Issue (2) : 317-322. DOI: 10.16098/j.issn.0529-1356.2021.02.025

综述

上腭发生的分子调控机制

许晨胡雪峰*

作者信息 +

Molecular mechanisms of palate development

XU Chen HU Xu-feng*

Author information +

文章历史 +

摘要

哺乳动物上腭的发生包括原生腭和次生腭的发生。其中，次生腭的发生涉及到高度动态的形态发生过程，分为腭突生长及模式化，两侧腭突的上抬/重定位，两侧腭突的黏附和融合形成次生腭等过程。近来的研究表明，上腭发育所需的基因，包括了声波刺猬蛋白（Shh）、成纤维细胞生长因子（FGF）、转化生长因子β（TGF-β）和Wnt信号通路，这些信号通路之间存在相互调节，信号通路的异常都会引起腭发育异常，甚至出现腭裂。本文中我们综述了上腭发育过程中各个阶段至关重要的基因及调控网络的研究进展。

Abstract

The mammalian palate develops from the primary palate and the secondary palate. Development of the mammalian secondary palate involves highly dynamic morphogenetic processes, including the outgrowth of palatal shelves from the oral side of the embryonic maxillary prominences, the elevation of the initially vertically oriented palatal shelves to the horizontal position above the embryonic tongue, and the subsequent adhesion and fusion of the paired palatal shelves at the midline to separate the oral cavity from the nasal cavity. In addition to identifying a large number of genes required for palate development, recent studies have begun to unravel the extensive cross-regulation of multiple signaling pathways, including sonic hedgehog(Shh), bone morphogenetic protein(BMP), fibroblast growth factor(FGF), transforming growth factor β(TGF-β), and Wnt signaling, during palatal shelf growth and patterning. Here we summarize major recent advances and integrate the genes and molecular pathways with the morhogenetic processes of palate development.

导出引用

许晨胡雪峰. 上腭发生的分子调控机制[J]. 解剖学报. 2021, 52(2): 317-322 https://doi.org/10.16098/j.issn.0529-1356.2021.02.025

XU Chen HU Xu-feng. Molecular mechanisms of palate development[J]. Acta Anatomica Sinica. 2021, 52(2): 317-322 https://doi.org/10.16098/j.issn.0529-1356.2021.02.025

中图分类号： Q593+.4

参考文献

［1］ Li C, Lan Y, Jiang R. Molecular and cellular mechanisms of palate development ［J］. J Dent Res, 2017, 96(11): 1184-1191.

［2］ Bush JO, Jiang R. Palatogenesis: morphogenetic and molecular mechanisms of secondary palate development ［J］. Development, 2012, 139(2): 231-243.

［3］ Lan Y, Jiang R. Sonic hedgehog signaling regulates reciprocal epithelial-mesenchymal interactions controlling palatal outgrowth ［J］. Development, 2009, 136(8): 1387-1396.

［4］ Lan Y, Ovitt CE, Cho ES, et al. Odd-skipped related 2 (Osr2) encodes a key intrinsic regulator of secondary palate growth and morphogenesis ［J］. Development, 2004, 131(13): 3207-3216.

［5］ Fu X, Xu J, Chaturvedi P, et al. Identification of Osr2 transcriptional target genes in palate development ［J］. J Dent Res, 2017, 96(12): 1451-1458.

［6］ Xu J, Liu H, Lan Y, et al. A Shh-Foxf-Fgf18-Shh molecular circuit regulating palate development ［J］. PLoS Genet, 2016, 12(1): e1005769.

［7］ Iwata J, Suzuki A, Pelikan RC, et al. Modulation of lipid metabolic defects rescues cleft palate in Tgfbr2 mutant mice ［J］. Hum Mol Genet, 2014, 23(1): 182-193.

［8］ Li Q, Ding J. Gene expression analysis reveals that formation of the mouse anterior secondary palate involves recruitment of cells from the posterior side ［J］. Int J Dev Biol, 2007, 51(2): 167-172.

［9］ Zhang Z, Song Y, Zhao X, et al. 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 ［J］. Development, 2002, 129(17): 4135-4146.

［10］ Xu J, Wang L, Li H, et al. Shox2 regulates osteogenic differentiation and pattern formation during hard palate development in mice ［J］. J Biol Chem, 2019, 294(48): 18294-18305.

［11］ He F, Xiong W, Yu X, et al. Wnt5a regulates directional cell migration and cell proliferation via Ror2-mediated noncanonical pathway in mammalian palate development ［J］. Development, 2008, 135(23): 3871-3879.

［12］ Nishihara H, Kobayashi N, Kimura-Yoshida C, et al. Coordinately co-opted multiple transposable elements constitute an enhancer for wnt5a expression in the mammalian secondary palate ［J］. PLoS Genet, 2016, 12(10): e1006380.

［13］ Cesario JM, Landin Malt A, Deacon LJ, et al. Lhx6 and Lhx8 promote palate development through negative regulation of a cell cycle inhibitor gene, p57Kip2 ［J］. Hum Mol Genet, 2015, 24(17): 5024-5039.

［14］ Wang Y. The preliminary study on the mechanism of craniomaxillofacial dysplasia induced by the overexpression of Fgf18 in cranial neural crest cells in mice ［D］. Fuzhou: Fujian Normal University, 2018.

王媛. 神经嵴细胞中过表达Fgf18导致小鼠颅颌面部发育严重异常及其相关机制的初步研究［D］. 福州：福建师范大学, 2018.

[15］ Brock LJ, Economou AD, Cobourne MT, et al. Mapping cellular processes in the mesenchyme during palatal development in the absence of Tbx1 reveals complex proliferation changes and perturbed cell packing and polarity ［J］. J Anat, 2016, 228(3): 464-473.

［16］ Lan Y, Zhang N, Liu H, et al. Golgb1 regulates protein glycosylation and is crucial for mammalian palate development ［J］. Development, 2016, 143(13): 2344-2355.

［17］ López-Gordillo Y, Maldonado E, Nogales L, et al. Maternal folic acid supplementation reduces the severity of cleft palate in Tgf-β null mutant mice ［J］. Pediatr Res, 2019, 85(4): 566-573.

［18］ Nik AM, Johansson JA, Ghiami M, et al. Foxf2 is required for secondary palate development and Tgfβ signaling in palatal shelf mesenchyme ［J］. Dev Biol, 2016, 415(1): 14-23.

［19］ Yu H, Smallwood PM, Wang Y, et al. Frizzled 1 and frizzled 2 genes function in palate, ventricular septum and neural tube closure: general implications for tissue fusion processes ［J］. Development, 2010, 137(21): 3707-3717.

［20］ Yang T, Jia Z, Bryant-Pike W, et al. Analysis of PRICKLE1 in human cleft palate and mouse development demonstrates rare and common variants involved in human malformations ［J］. Mol Genet Genomic Med, 2014, 2(2): 138-151.

［21］ Jiang Z, Pan L, Chen X, et al. Wnt6 influences the viability of mouse embryonic palatal mesenchymal cells via the β-catenin pathway ［J］. Exp Ther Med, 2017, 14(6): 5339-5344.

［22］ Sedgwick AE, D’souza-Schorey C. Wnt signaling in cell motility and invasion: drawing parallels between development and cancer ［J］. Cancers (Basel), 2016, 8(9): 80.

［23］ Casey LM, Lan Y, Cho E-S, et al. Jag2-Notch1 signaling regulates oral epithelial differentiation and palate development ［J］. Dev Dyn, 2006, 235(7): 1830-1844.

［24］ Kousa YA, Schutte BC. Toward an orofacial gene regulatory network ［J］. Dev Dyn, 2016, 245(3): 220-232.

［25］ Richardson RJ, Dixon J, Jiang R, et al. Integration of IRF6 and Jagged2 signalling is essential for controlling palatal adhesion and fusion competence ［J］. Hum Mol Genet, 2009, 18(14): 2632-2642.

［26］ Richardson RJ, Hammond NL, Coulombe PA, et al. Periderm prevents pathological epithelial adhesions during embryogenesis ［J］. J Clin Invest, 2014, 124(9): 3891-3900.

［27］ Hall EG, Wenger LW, Wilson NR, et al. SPECC1L regulates palate development downstream of IRF6 ［J］. Human Mol Genet, 2020, 29(5): 845-858.

［28］ YAN C, DENG-QI H, LI-YA C, et al. Transforming growth factor alpha Taq Ⅰ polymorphisms and nonsyndromic cleft lip and/or palate risk: a meta-analysis ［J］. Cleft Palate Craniofac J, 2018, 55(6): 814-820.

［29］ Lane J, Yumoto K, Pisano J, et al. Control elements targeting Tgfb3 expression to the palatal epithelium are located intergenically and in introns of the upstream Ift43 gene ［J］. Front Physiol, 2014, 5:258.

［30］ Kaartinen V, Voncken JW, Shuler C, et al. Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction ［J］. Nat Genet, 1995, 11(4): 415-421.

［31］ Proetzel G, Pawlowski SA, Wiles MV, et al. Transforming growth factor-beta 3 is required for secondary palate fusion ［J］. Nat Genet, 1995, 11(4): 409-414.

［32］ Kaartinen V, Cui XM, Heisterkamp N, et al. Transforming growth factor-beta3 regulates transdifferentiation of medial edge epithelium during palatal fusion and associated degradation of the basement membrane ［J］. Dev Dyn, 1997, 209(3): 255-260.

［33］ Hu L, Liu J, Li Z, et al. TGFβ3 regulates periderm removal through ΔNp63 in the developing palate ［J］. J Cell Physiol, 2015, 230(6): 1212-1225.

［34］ Lane J, Yumoto K, Azhar M, et al. Tak1, Smad4 and Trim33 redundantly mediate TGF-β3 signaling during palate development ［J］. Dev Biol, 2015, 398(2): 231-241.

［35］ Iwata JI, Suzuki A, Pelikan RC, et al. Smad4-Irf6 genetic interaction and TGFβ-mediated IRF6 signaling cascade are crucial for palatal fusion in mice ［J］. Development, 2013, 140(6): 1220-1230.

［36］ JIN JZ, WARNER DR, LU Q, et al. Deciphering TGF-β3 function in medial edge epithelium specification and fusion during mouse secondary palate development ［J］. Dev Dyn, 2014, 243(12): 1536-1543.

［37］ Murray SA, Oram KF, Gridley T. Multiple functions of Snail family genes during palate development in mice ［J］. Development, 2007, 134(9): 1789-1797.

［38］ Jalali A, Zhu X, Liu C, et al. Induction of palate epithelial mesenchymal transition by transforming growth factor β3 signaling ［J］. Dev Growth Differ, 2012, 54(6): 633-648.

［39］ Mima J, Koshino A, Oka K, et al. Regulation of the epithelial adhesion molecule CEACAM1 is important for palate formation ［J］. PLoS One, 2013, 8(4): e61653.

［40］ Ahmed S, Liu CC, Nawshad A. Mechanisms of palatal epithelial seam disintegration by transforming growth factor (TGF) beta3 ［J］. Dev Biol, 2007, 309(2): 193-207.

［41］ Nakajima A, Tanaka E, Ito Y, et al. The expression of TGF-β3 for epithelial-mesenchyme transdifferentiated MEE in palatogenesis ［J］. J Mol Histol, 2010, 41(6): 343-355.

［42］ Kim S, Lewis AE, Singh V, et al. Convergence and extrusion are required for normal fusion of the mammalian secondary palate ［J］. PLoS Biol, 2015, 13(4): e1002122.

［43］ Noda K, Mishina Y, Komatsu Y. Constitutively active mutation of ACVR1 in oral epithelium causes submucous cleft palate in mice ［J］. Dev Biol, 2016, 415(2): 306-313.