国际口腔医学杂志

国际口腔医学杂志 ›› 2019, Vol. 46 ›› Issue (5): 546-551.doi: 10.7518/gjkq.2019049

• 综述 • 上一篇    下一篇

腭突上抬的发生及其分子生物学机制

王亚红,李承浩,石冰()   

  1. 口腔疾病研究国家重点实验室 国家口腔疾病临床医学研究中心 四川大学华西口腔医院唇腭裂外科 成都 610041
  • 收稿日期:2018-11-08 修回日期:2019-05-21 出版日期:2019-09-01 发布日期:2019-09-10
  • 通讯作者: 石冰
  • 作者简介:王亚红,医师,硕士,Email： 13032888560@163.com
  • 基金资助:
    四川省科技重点研发计划(2019YFS0355)

Research progress on the mechanism of palatal shelf elevation

Wang Yahong,Li Chenghao,Shi Bing()   

  1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Cleft Lip and Palate Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2018-11-08 Revised:2019-05-21 Online:2019-09-01 Published:2019-09-10
  • Contact: Bing Shi
  • Supported by:
    This study was supported by Science and Technology Key Research and Development Program of Sichuan Province(2019YFS0355)

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摘要：

腭裂是由遗传和环境因素共同作用而导致的一种多基因遗传病,腭的发生包括腭突生长、上抬和融合,其中任何一个阶段的异常都会导致腭裂发生,尤其腭突上抬异常是导致腭裂发生最常见的原因之一。近年来,腭生长和腭融合的机制是腭发育领域的研究热点,国内外学者在此方面也取得了许多进展,与之相比,由于相关细胞及分子学基础研究的缺乏,关于腭突上抬的研究较少,且进展甚微。因此,本文归纳了近年来国内外学者的研究成果,对腭突上抬的发生过程及其相关的分子生物学机制的研究进展进行综述。

关键词: 小鼠, 腭裂, 腭发生, 继发腭, 腭上抬

Abstract:

Cleft palate is a polygenic genetic disease caused by genetic and environmental interaction. The formation of mammalian secondary palate involves multiple developmental events, including growth, elevation and fusion. Perturbation of any of these processes could cause cleft palate. Defects related to the elevation process commonly cause cleft palate. In recent years, the mechanism of palatal shelf growth and fusion has been a research hotspot in palate development. Compared with advances in those aspects, little progress has been achieved in palatal shelf elevation. Although many mutant mice show delay or defects in shelf elevation, the mechanism of this process still remains elusive because of the scarce knowledge about its cellular and molecular basis. In this paper, we summarise major recent advances and integrate the related genes and molecular pathways with the cellular and morphogenetic processes of palatal shelf elevation.

Key words: mouse, cleft palate, palatogenesis, secondary palate, palatal shelf elevation

中图分类号: 

  • Q132.4
[1] Ferguson MW . Palate development[J]. Development, 1988,103(Suppl):41-60.
[2] Hilliard SA, Yu L, Gu S , et al. Regional regulation of palatal growth and patterning along the anterior-posterior axis in mice[J]. J Anat, 2005,207(5):655-667.
[3] Chai Y, Maxson RE Jr . Recent advances in craniofacial morphogenesis[J]. Dev Dyn, 2006,235(9):2353-2375.
[4] Gritli-Linde A . Molecular control of secondary palate development[J]. Dev Biol, 2007,301(2):309-326.
[5] Dixon MJ, Marazita ML, Beaty TH , et al. Cleft lip and palate: understanding genetic and environmental influences[J]. Nat Rev Genet, 2011,12(3):167-178.
[6] Lan Y, Xu J, Jiang R . Cellular and molecular mechanisms of palatogenesis[J]. Curr Top Dev Biol, 2015,115:59-84.
[7] Bush JO, Jiang R . Palatogenesis: morphogenetic and molecular mechanisms of secondary palate develop-ment[J]. Development, 2012,139(2):231-243.
[8] Ferguson MW . The mechanism of palatal shelf elevation and the pathogenesis of cleft palate[J]. Virchows Arch A Pathol Anat Histol, 1977,375(2):97-113.
[9] Diewert VM . A quantitative coronal plane evaluation of craniofacial growth and spatial relations during secondary palate development in the rat[J]. Arch Oral Biol, 1978,23(8):607-629.
[10] Gritli-Linde A . The etiopathogenesis of cleft lip and cleft palate: usefulness and caveats of mouse models[J]. Curr Top Dev Biol, 2008,84:37-138.
[11] Yu K, Ornitz DM . Histomorphological study of palatal shelf elevation during murine secondary palate formation[J]. Dev Dyn, 2011,240(7):1737-1744.
[12] Chiquet M, Blumer S, Angelini M , et al. Mesenchymal remodeling during palatal shelf elevation revealed by extracellular matrix and F-actin expression patterns[J]. Front Physiol, 2016,7:392.
[13] Coleman RD . Development of the rat palate[J]. Anat Rec, 1965,151:107-117.
[14] Kochhar DM, Johnson EM . Morphological and autoradiographic studies of cleft palate induced in rat embryos by maternal hypervitaminosis A[J]. J Embryol Exp Morphol, 1965,14(3):223-238.
[15] Chou MJ, Kosazuma T, Takigawa T , et al. Palatal shelf movement during palatogenesis: a fate map of the fetal mouse palate cultured in vitro[J]. Anat Embryol (Berl), 2004,208(1):19-25.
[16] Jin JZ, Tan M, Warner DR , et al. Mesenchymal cell remodeling during mouse secondary palate reorientation[J]. Dev Dyn, 2010,239(7):2110-2117.
[17] 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.
[18] Brinkley LL, Vickerman MM . Elevation of lesioned palatal shelves in vitro[J]. J Embryol Exp Morphol, 1979,54:229-240.
[19] Iseki S, Ishii-Suzuki M, Tsunekawa N , et al. Experimental induction of palate shelf elevation in glutamate decarboxylase 67-deficient mice with cleft palate due to vertically oriented palatal shelf[J]. Birth Defects Res A Clin Mol Teratol, 2007,79(10):688-695.
[20] Kouskoura T, El Fersioui Y, Angelini M , et al. Dislocated tongue muscle attachment and cleft palate formation[J]. J Dent Res, 2016,95(4):453-459.
[21] Luke DA . Epithelial proliferation and development of rugae in relation to palatal shelf elevation in the mouse[J]. J Anat, 1984,138(Pt 2):251-258.
[22] Greene RM, Kochhar DM . Spatial relations in the oral cavity of cortisone-treated mouse fetuses during the time of secondary palate closure[J]. Teratology, 1973,8(2):153-161.
[23] Brinkley L, Basehoar G, Branch A , et al. A new in vitro system for studying secondary palate development[J]. J Embryol Exp Morphol, 1975,34(2):485-495.
[24] He F, Xiong W, Wang Y , et al. Epithelial Wnt/β- catenin signaling regulates palatal shelf fusion through regulation of Tgfβ3 expression[J]. Dev Biol, 2011,350(2):511-519.
[25] Lessard JL, Wee EL, Zimmerman EF . Presence of contractile proteins in mouse fetal palate prior to shelf elevation[J]. Teratology, 1974,9(1):113-125.
[26] Ferguson MW . Palatal shelf elevation in the Wistar rat fetus[J]. J Anat, 1978,125(Pt 3):555-577.
[27] Brinkley LL, Vickerman MM . The effects of chlorcyclizine-induced alterations of glycosaminoglycans on mouse palatal shelf elevation in vivo and in vitro[J]. J Embryol Exp Morphol, 1982,69:193-213.
[28] Snyder-Warwick AK, Perlyn CA, Pan J , et al. Analysis of a gain-of-function FGFR2 Crouzon mutation provides evidence of loss of function activity in the etiology of cleft palate[J]. Proc Natl Acad Sci USA, 2010,107(6):2515-2520.
[29] Li C, Lan Y, Krumlauf R , et al. Modulating Wnt signaling rescues palate morphogenesis in Pax9 mutant mice[J]. J Dent Res, 2017,96(11):1273-1281.
[30] 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.
[31] Matsumura K, Taketomi T, Yoshizaki K , et al. Sprouty2 controls proliferation of palate mesenchymal cells via fibroblast growth factor signaling[J]. Biochem Biophys Res Commun, 2011,404(4):1076-1082.
[32] Li C, Lan Y, Jiang R . Molecular and cellular mechanisms of palate development[J]. J Dent Res, 2017,96(11):1184-1191.
[33] Lane J, Kaartinen V . Signaling networks in palate development[J]. Wiley Interdiscip Rev Syst Biol Med, 2014,6(3):271-278.
[34] Rice R, Spencer-Dene B, Connor EC , et al. Disruption of Fgf10/Fgfr2b-coordinated epithelial-mesenchymal interactions causes cleft palate[J]. J Clin Invest, 2004,113(12):1692-1700.
[35] Lan Y, Jiang R . Sonic hedgehog signaling regulates reciprocal epithelial-mesenchymal interactions controlling palatal outgrowth[J]. Development, 2009,136(8):1387-1396.
[36] 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.
[37] Zoupa M, Seppala M, Mitsiadis T , et al. Tbx1 is expressed at multiple sites of epithelial-mesenchymal interaction during early development of the facial complex[J]. Int J Dev Biol, 2006,50(5):504-510.
[38] Goudy S, Law A, Sanchez G , et al. Tbx1 is necessary for palatal elongation and elevation[J]. Mech Dev, 2010,127(5/6):292-300.
[39] Peters H, Neubüser A, Kratochwil K , et al. Pax9-deficient mice lack pharyngeal pouch derivatives and teeth and exhibit craniofacial and limb abnormalities[J]. Genes Dev, 1998,12(17):2735-2747.
[40] 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.
[41] Zhou J, Gao Y, Lan Y , et al. Pax9 regulates a molecular network involving Bmp4, Fgf10, Shh signaling and the Osr2 transcription factor to control palate morphogenesis[J]. Development, 2013,140(23):4709-4718.
[42] Almaidhan A, Cesario J, Landin Malt A , et al. Neural crest-specific deletion of Ldb1 leads to cleft secondary palate with impaired palatal shelf elevation[J]. BMC Dev Biol, 2014,14:3.
[43] Jin JZ, Li Q, Higashi Y , et al. Analysis of Zfhx1a mutant mice reveals palatal shelf contact-independent medial edge epithelial differentiation during palate fusion[J]. Cell Tissue Res, 2008,333(1):29-38.
[44] 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.
[45] 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.
[46] 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.
[47] Liu Y, Wang M, Zhao W , et al. Gpr177-mediated Wnt signaling is required for secondary palate development[J]. J Dent Res, 2015,94(7):961-967.
[48] 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). doi: 10.3390/cancers8090080.
[49] Tang Q, Li L, Jin C , et al. Role of region-distinctive expression of Rac1 in regulating fibronectin arrangement during palatal shelf elevation[J]. Cell Tissue Res, 2015,361(3):857-868.
[50] Liu KJ, Arron JR, Stankunas K , et al. Chemical rescue of cleft palate and midline defects in conditional GSK-3beta mice[J]. Nature, 2007,446(7131):79-82.
[51] He F, Popkie AP, Xiong W , et al. Gsk3β is required in the epithelium for palatal elevation in mice[J]. Dev Dyn, 2010,239(12):3235-3246.
[52] Jia S, Zhou J, Fanelli C , et al. Small-molecule Wnt agonists correct cleft palates in Pax9 mutant mice in utero[J]. Development, 2017,144(20):3819-3828.
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