抑制Wnt/β-catenin信号通路对上唇发育的影响
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摘要
目的:探讨通过抑制Wnt/β-catenin信号表达对上唇发育的影响。方法:通过在H-H22阶段的鸡胚上颌突植入浸有XAV939、DMSO的微珠以及只作切口不植入微珠,构建实验组、对照组和假实验组,并继续孵育至H-H38阶段,体视显微镜以及mirco-CT观察并记录胚胎上唇的发育情况。结果:Wnt/β-catenin信号受抑制后,H-H28阶段的鸡胚植入侧上颌突与中鼻突和侧鼻突的融合延迟,H-H38阶段的鸡胚植入侧的上唇出现发育延缓,面中线偏向植入侧;实验组的正常侧、对照组以及假实验组的双侧上唇发育未受影响。结论:在鸡胚上唇发育过程中,通过抑制Wnt/β-catenin信号表达,可延迟上颌突和中鼻突的融合,使上唇发育延迟,进而导致上颌骨发育不足或畸形。
Objective: To investigate the effect of inhibiting the Wnt/β-catenin signal on the growth of upper lip. Methods: The maxillary prominence of chicken embryo was implanted the beads impregnated with XAV939 and DMSO and implanted without beads into in the H-H22 stage. The experimental group, control group, and sham group were constructed separately. The incubation was continued until the H-H38 stage. The development of the upper lip of the embryo was observed and recorded by stereomicroscopy and micro-CT. Results: After the Wnt/β-catenin signal was inhibited, the fusion of the maxillary prominence and the frontonasal mass and the lateral nasal prominence of the chicken embryo implanted at the H-H28 stage was delayed, and the upper lip of the chicken embryo implanted-side of the H-H38 stage was delayed in development. The midline was biased toward the implanted side. In addition, the development of the bilateral upper lip of the normal side of the experimental group, the control group, and the sham group was not affected. Conclusion: In the development of the upper lip of the chicken embryo, by inhibition of Wnt/β-catenin signal, the fusion of the maxillary prominence, and the frontonasal mass can be delayed so that the development of the upper lip was delayed, leading to the insufficient development or deformity of maxilla bone.
Objective: To investigate the effect of inhibiting the Wnt/β-catenin signal on the growth of upper lip. Methods: The maxillary prominence of chicken embryo was implanted the beads impregnated with XAV939 and DMSO and implanted without beads into in the H-H22 stage. The experimental group, control group, and sham group were constructed separately. The incubation was continued until the H-H38 stage. The development of the upper lip of the embryo was observed and recorded by stereomicroscopy and micro-CT. Results: After the Wnt/β-catenin signal was inhibited, the fusion of the maxillary prominence and the frontonasal mass and the lateral nasal prominence of the chicken embryo implanted at the H-H28 stage was delayed, and the upper lip of the chicken embryo implanted-side of the H-H38 stage was delayed in development. The midline was biased toward the implanted side. In addition, the development of the bilateral upper lip of the normal side of the experimental group, the control group, and the sham group was not affected. Conclusion: In the development of the upper lip of the chicken embryo, by inhibition of Wnt/β-catenin signal, the fusion of the maxillary prominence, and the frontonasal mass can be delayed so that the development of the upper lip was delayed, leading to the insufficient development or deformity of maxilla bone.
引文
[1] Assis Machado R,de Toledo IP,Martelli-Júnior H,et al.Potential genetic markers for nonsyndromic oral clefts in the Brazilian population:A systematic review and meta-analysis [J].Birth Defects Res,2018,110(10):827-839.
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[11] Hamburger V,Hamilton HL.A series of normal stages in the development of the chick embryo [J].J Morphol,1951,88(1):49-92.
[12] Lan Y,Xu J,Jiang R.Cellular and molecular mechanisms of palatogenesis [J].Curr Top Dev Biol,2015,115:59-84.
[13] 朴正国,Seok-Kee Baik,邹瑞,等.O-GlcNAc对上唇发育过程中上皮间叶转化影响的研究[J].口腔医学研究,2016,32(3):285-289.
[14] Abramyan J,Thivichon-Prince B,Richman JM.Diversity in primary palate ontogeny of amniotes revealed with 3D imaging [J].J Anat,2015,226(5):420-433.
[15] Jarvinen E,Shimomura-Kuroki J,Balic A,et al.Mesenchymal Wnt/β-catenin signaling limits tooth number [J].Development,2018,145(4):pii:dev158048.
[16] Machado RA,de Freitas EM,de Aquino SN,et al.Clinical relevance of breast and gastric cancer-associated polymorphisms as potential susceptibility markers for oral clefts in the Brazilian population [J].BMC Med Genet,2017,18(1):39.
[17] Fontoura C,Silva RM,Granjeiro JM,et al.Association of WNT9B gene polymorphisms with nonsyndromic cleft lip with or without cleft palate in Brazilian nuclear families [J].Cleft Palate Craniofac J,2015,52(1):44-48.
[18] Lin C,Fisher AV,Yin Y,et al.The inductive role of Wnt-beta-catenin signaling in the formation of oral apparatus [J].Dev Biol,2011,356(1):40-50.
[19] Geetha-Loganathan P,Nimmagadda S,Fu K,et al.Avian facial morphogenesis is regulated by c-Jun N-terminal kinase/planar cell polarity (JNK/PCP) wingless-related (WNT) signaling [J].J Biol Chem,2014,289(35):24153-24167.
[20] Eckei G,B?ing M,Brand-Saberi B,et al.Expression pattern of Axin2 during chicken development [J].PLoS One,2016,11(9):e0163610.
[2] 刘丽萍,杜杨格,杨小红,等.产前诊断唇腭裂畸形的研究进展[J].口腔医学研究,2017,33(1):112-114.
[3] Geetha-Loganathan P,Nimmagadda S,Antoni L,et al.Expression of WNT signalling pathway genes during chicken craniofacial development [J].Dev Dyn,2009,238(5):1150-1165.
[4] Han Y,Zhou L,Ma L,et al.The axis inhibition protein 2 polymorphisms and non-syndromic orofacial clefts susceptibility in a Chinese Han population [J].J Oral Pathol Med,2014,43(7):554-560.
[5] Kurosaka H,Iulianella A,Williams T,et al.Disrupting hedgehog and WNT signaling interactions promotes cleft lip pathogenesis [J].J Clin Invest,2014,124(4):1660-1671.
[6] Machado RA,de Freitas EM,de Aquino SN,et al.Clinical relevance of breast and gastric cancer-associated polymorphisms as potential susceptibility markers for oral clefts in the Brazilian population [J].BMC Med Genet,2017,18(1):39.
[7] Rafighdoost H,Hashemi M,Asadi H,et al.Association of single nucleotide polymorphisms in AXIN2,BMP4,and IRF6 with Non-Syndromic Cleft Lip with or without Cleft Palate in a sample of the southeast Iranian population [J].J Appl Oral Sci,2017,25(6):650-656.
[8] Huang SM,Mishina YM,Liu S,et al.Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling [J].Nature,2009,461(7264):614-620.
[9] Suebsoonthron J,Jaroonwitchawan T,Yamabhai M,et al.Inhibition of WNT signaling reduces differentiation and induces sensitivity to doxorubicin in human malignant neuroblastoma SH-SY5Y cells [J].Anticancer Drugs,2017,28(5):469-479.
[10] Wang R,Wu Y,Huang W,et al.MicroRNA-940 targets INPP4A or GSK3beta and activates the Wnt/beta-catenin pathway to regulate the malignant behavior of bladder cancer cells [J].Oncol Res,2018,26(1):145-155.
[11] Hamburger V,Hamilton HL.A series of normal stages in the development of the chick embryo [J].J Morphol,1951,88(1):49-92.
[12] Lan Y,Xu J,Jiang R.Cellular and molecular mechanisms of palatogenesis [J].Curr Top Dev Biol,2015,115:59-84.
[13] 朴正国,Seok-Kee Baik,邹瑞,等.O-GlcNAc对上唇发育过程中上皮间叶转化影响的研究[J].口腔医学研究,2016,32(3):285-289.
[14] Abramyan J,Thivichon-Prince B,Richman JM.Diversity in primary palate ontogeny of amniotes revealed with 3D imaging [J].J Anat,2015,226(5):420-433.
[15] Jarvinen E,Shimomura-Kuroki J,Balic A,et al.Mesenchymal Wnt/β-catenin signaling limits tooth number [J].Development,2018,145(4):pii:dev158048.
[16] Machado RA,de Freitas EM,de Aquino SN,et al.Clinical relevance of breast and gastric cancer-associated polymorphisms as potential susceptibility markers for oral clefts in the Brazilian population [J].BMC Med Genet,2017,18(1):39.
[17] Fontoura C,Silva RM,Granjeiro JM,et al.Association of WNT9B gene polymorphisms with nonsyndromic cleft lip with or without cleft palate in Brazilian nuclear families [J].Cleft Palate Craniofac J,2015,52(1):44-48.
[18] Lin C,Fisher AV,Yin Y,et al.The inductive role of Wnt-beta-catenin signaling in the formation of oral apparatus [J].Dev Biol,2011,356(1):40-50.
[19] Geetha-Loganathan P,Nimmagadda S,Fu K,et al.Avian facial morphogenesis is regulated by c-Jun N-terminal kinase/planar cell polarity (JNK/PCP) wingless-related (WNT) signaling [J].J Biol Chem,2014,289(35):24153-24167.
[20] Eckei G,B?ing M,Brand-Saberi B,et al.Expression pattern of Axin2 during chicken development [J].PLoS One,2016,11(9):e0163610.