脊椎动物胚胎期脊椎的形成及信号通路调控机制

doi:10.11843/j.issn.0366-6964.2021.06.002

摘要/Abstract

摘要： 脊椎是哺乳动物整个躯体的支柱，具有较高的遗传力，且可对胴体长产生重要影响。不同物种之间的脊椎数量互不相同，甚至同一物种如猪、羊等物种内也存在变异。脊椎数主要受胚胎体节发育时期体节数量的影响，为了进一步探究脊椎形成和数量变异的调控机制，本文综述了脊椎的胚胎发育过程、重要中间结构体节的形成和调控因素，旨在阐明脊椎形成和发育的调控机制，进而为经济动物脊椎数的选育改良提供理论依据和研究思路。

关键词: 脊椎, 胚胎发育, 体节, 信号通路

Abstract: The spine is the backbone of the mammalian body which has high heritability and important impact on carcass length. Its number varies among species, even within the same species, such as pigs and sheep. The number of vertebra is affected by the number of somites during the embryo development. In order to further explore the regulation mechanism of spine formation and quantity variation, this article reviews the embryonic development process of the spine, the formation and regulation of important intermediate structural somites. The aim of this review is to clarify the regulation mechanism of spine formation and development and provide theoretical basis and ideas for number of vertebrae breeding in economic animals.

Key words: spine, embryonic development, somites, signal pathway

中图分类号:

S852.2

刘倩, 岳静伟, 牛乃琪, 王立贤, 张龙超. 脊椎动物胚胎期脊椎的形成及信号通路调控机制[J]. 畜牧兽医学报, 2021, 52(6): 1461-1470.

LIU Qian, YUE Jingwei, NIU Naiqi, WANG Lixian, ZHANG Longchao. The Regulation Mechanism and Signal Pathway for Spine Formation in Vertebrate Embryo[J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(6): 1461-1470.

参考文献 75

[1]	YOSHIOKA-KOBAYASHI K,MATSUMIYA M,NIINO Y,et al.Coupling delay controls synchronized oscillation in the segmentation clock[J].Nature,2020,580(7801):119-123.
[2]	DURSTON A J,PERES J,COHEN M H.Spiral waves and vertebrate embryonic handedness[J].J Biosci,2018,43(2):375-390.
[3]	DUAN Y Y,ZHANG H,ZHANG Z,et al.Vrtn is required for the development of thoracic vertebrae in mammals[J].Int J Biol Sci,2018,14(6):667-681.
[4]	LI C Y,LI M,LI X Y,et al.Whole-genome resequencing reveals loci associated with thoracic vertebrae number in sheep[J].Front Genet,2019,10:674.
[5]	NELEMANS B K A,SCHMITZ M,TAHIR H,et al.Somite division and new boundary formation by mechanical strain[J]. iScience, 2020,23(4):100976.
[6]	GOMEZ C,POURQUIÉ O.Developmental control of segment numbers in vertebrates[J].J Exp Zool B Mol Dev Evol,2009, 312(6):533-544.
[7]	DEQUÉANT M L,POURQUIÉ O.Segmental patterning of the vertebrate embryonic axis[J].Nat Rev Genet,2008,9(5):370-382.
[8]	VROOMANS R M A,HOGEWEG P,TEN TUSSCHER K H W J.Around the clock:gradient shape and noise impact the evolution of oscillatory segmentation dynamics[J].EvoDevo,2018,9:24.
[9]	COOKE J,ZEEMAN E C.A clock and wavefront model for control of the number of repeated structures during animal morphogenesis[J].J Theor Biol,1976,58(2):455-476.
[10]	PALLA A,BLAU H.The clock that controls spine development modelled in a dish[J].Nature,2020,580(7801):32-34.
[11]	ALEXANDER T,NOLTE C,KRUMLAUF R.Hox genes and segmentation of the hindbrain and axial skeleton[J].Annu Rev Cell Dev Biol,2009,25:431-456.
[12]	ANDERSON M J,SCHIMMANG T,LEWANDOSKI M.An FGF3-BMP signaling axis regulates caudal neural tube closure,neural crest specification and anterior-posterior axis extension[J].PLoS Genet,2016,12(5):e1006018.
[13]	DIAZ-CUADROS M,WAGNER D E,BUDJAN C,et al.In vitro characterization of the human segmen-tation clock[J].Nature, 2020,580(7801):113-118.
[14]	张红卫.发育生物学[M].2版.北京:高等教育出版社,2006.ZHANG H W.Developmental biology[M].2nd ed.Beijing:Higher Education Press,2006.(in Chinese)
[15]	AMINI Z,MAHDAVI-SHAHRI N,LARI R,et al.The effects of lead on the development of somites in chick embryos (Gallus gallus domesticus) under in vitro conditions:a histological study[J].Toxicol Res (Camb),2019,8(3):373-380.
[16]	DURSTON A J.Two tier Hox collinearity mediates vertebrate axial patterning[J].Front Cell Dev Biol,2018,6:102.
[17]	HASHIGUCHI M,MULLINS M C.Anteroposterior and dorsoventral patterning are coordinated by an identical patterning clock[J].Development,2013,140(9):1970-1980.
[18]	DENANS N,IIMURA T,POURQUIÉ O.Hox genes control vertebrate body elongation by collinear Wnt repression[J]. Elife,2015,4:e04379.
[19]	WYMEERSCH F J,SKYLAKI S,HUANG Y L,et al.Transcriptionally dynamic progenitor populations organised around a stable niche drive axial patterning[J].Development,2019,146(1):dev168161.
[20]	MOREAU C,CALDARELLI P,ROCANCOURT D,et al.Timed collinear activation of Hox genes during gastrulation controls the avian forelimb position[J].Curr Biol,2019,29(1):35-50.e1-e4.
[21]	DURSTON A J.What are the roles of retinoids,other morphogens,and Hox genes in setting up the vertebrate body axis?[J].Genesis,2019,57(7-8):e23296.
[22]	MISHINA Y,HANKS M C,MIURA S,et al.Generation of Bmpr/Alk3 conditional knockout mice[J].Genesis, 2002,32(2):69-72.
[23]	YU P B,DENG D Y,LAI C S,et al.BMP type I receptor inhibition reduces heterotopic ossification[J].Nat Med,2008,14(12):1363-1369.
[24]	MISHINA Y,STARBUCK M W,GENTILE M A,et al.Bone morphogenetic protein type IA receptor signaling regulates postnatal osteoblast function and bone remodeling[J].J Biol Chem,2004,279(26):27560-27566.
[25]	MISHINA Y.Function of bone morphogenetic protein signaling during mouse development[J].Front Biosci,2003,8:d855-d869.
[26]	MIURA S,DAVIS S,KLINGENSMITH J,et al.BMP signaling in the epiblast is required for proper recruitment of the prospective paraxial mesoderm and development of the somites[J].Development,2006,133(19):3767-3775.
[27]	QI H B,JIN M,DUAN Y Q,et al.FGFR3 induces degradation of BMP type I receptor to regulate skeletal development[J].Biochim Biophys Acta Mol Cell Res,2014,1843(7):1237-1247.
[28]	BÖHMER C.Correlation between Hox code and vertebral morphology in the mouse:towards a universal model for synapsida[J].Zoological Lett,2017,3:8.
[29]	KESSEL M,GRUSS P.Homeotic transformations of murine vertebrae and concomitant alteration of Hox codes induced by retinoic acid[J].Cell,1991,67(1):89-104.
[30]	JUAN A H,LEI H,BHARGAVA P,et al.Multiple roles of Hoxc8 in skeletal development[J].Ann N Y Acad Sci,2006, 1068(1):87-94.
[31]	WELLIK D M,CAPECCHI M R.Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton[J]. Science,2003,301(5631):363-367.
[32]	MCINTYRE D C,RAKSHIT S,YALLOWITZ A R,et al.Hox patterning of the vertebrate rib cage[J].Development, 2007,134(16):2981-2989.
[33]	ZÁKÁNY J,KMITA M,ALARCON P,et al.Localized and transient transcription of Hox genes suggests a link between patterning and the segmentation clock[J].Cell,2001,106(2):207-217.
[34]	AULEHLA A,WEHRLE C,BRAND-SABERI B,et al.Wnt3a plays a major role in the segmentation clock controlling somitogenesis[J].Dev Cell,2003,4(3):395-406.
[35]	CHU L F,MAMOTT D,NI Z J,et al.An in vitro human segmentation clock model derived from embryonic stem cells[J].Cell Rep,2019,28(9):2247-2255.e1-e5.
[36]	XI H B,FUJIWARA W,GONZALEZ K,et al.In vivo human somitogenesis guides somite development from hPSCs[J].Cell Rep,2017,18(6):1573-1585.
[37]	MORGANI S M,SAIZ N,GARG V,et al.A Sprouty4 reporter to monitor FGF/ERK signaling activity in ESCs and mice[J].Dev Biol,2018,441(1):104-126.
[38]	SONNEN K F,LAUSCHKE V M,URAJI J,et al.Modulation of phase shift between Wnt and notch signaling oscillations controls mesoderm segmentation[J].Cell,2018,172(5):1079-1090.e1-e3.
[39]	DUBRULLE J,MCGREW M J,POURQUIÉ O.FGF signaling controls somite boundary position and regulates segmentation clock control of spatio-temporal Hox gene activation[J].Cell,2001,106(2):219-232.
[40]	NAOKI H,AKIYAMA R,SARI D W K,et al.Noise-resistant developmental reproducibility in vertebrate somite formation[J]. PLoS Comput Biol,2019,15(2):e1006579.
[41]	GRUSS P,KESSEL M.Axial specification in higher vertebrates[J].Curr Opin Genet Dev,1991,1(2):204-210.
[42]	KAWAKAMI Y,RAYA Á,RAYA R M,et al.Retinoic acid signalling links left-right asymmetric patterning and bilaterally symmetric somitogenesis in the zebrafish embryo[J].Nature,2005,435(7039):165-171.
[43]	VERMOT J,POURQUIÉ O.Retinoic acid coordinates somitogenesis and left-right patterning in vertebrate embryos[J]. Nature,2005,435(7039):215-220.
[44]	BRUECKNER M,D'EUSTACHIO P,HORWICH A L.Linkage mapping of a mouse gene,iv,that controls left-right asymmetry of the heart and viscera[J].Proc Natl Acad Sci U S A,1989,86(13):5035-5038.
[45]	RANKIN S A,MCCRACKEN K W,LUEDEKE D M,et al.Timing is everything:reiterative Wnt,BMP and RA signaling regulate developmental competence during endoderm organogenesis[J].Dev Biol,2018,434(1):121-132.
[46]	KESKIN S,DEVAKANMALAI G S,KWON S B,et al.Noise in the vertebrate segmentation clock is boosted by time delays but tamed by notch signaling[J].Cell Rep,2018,23(7):2175-2185.e1-e4.
[47]	CARRIERI F A,MURRAY P J,DITSOVA D,et al.CDK1 and CDK2 regulate NICD1 turnover and the periodicity of the segmentation clock[J].EMBO Rep,2019,20(7):e46436.
[48]	NAOKI H,MATSUI T.Somite boundary determination in normal and clock-less vertebrate embryos[J].Dev Growth Differ,2020,62(3):177-187.
[49]	HORMUTH D A,WEIS J A,BARNES S L,et al.A mechanically coupled reaction-diffusion model that incorporates intra-tumoural heterogeneity to predict in vivo glioma growth[J].J R Soc Interface,2017,14(128):20161010.
[50]	LI D L,HALLACK A,CLEVELAND R O,et al.3D multicellular model of shock wave-cell interaction[J].Acta Biomater,2018,77:282-291.
[51]	SCHNELL S,MAINI P K.Clock and induction model for somitogenesis[J].Dev Dyn,2000,217(4):415-420.
[52]	LIAO B K,OATES A C.Delta-Notch signalling in segmentation[J].Arthropod Struct Dev,2017,46(3):429-447.
[53]	PAIS-DE-AZEVEDO T,MAGNO R,DUARTE I,et al.Recent advances in understanding vertebrate segmentation[version 1; peer review:3 approved] [J].F1000Res,2018,7:97.
[54]	VENZIN O F,OATES A C.What are you synching about? Emerging complexity of notch signaling in the segmentation clock[J].Dev Biol,2020,460(1):40-54.
[55]	MORRISS-KAY G M,MURPHY P,HILL R E,et al.Effects of retinoic acid excess on expression of Hox-2.9 and Krox-20 and on morphological segmentation in the hindbrain of mouse embryos[J].EMBO J,1991,10(10):2985-2995.
[56]	MATSUDA M,YAMANAKA Y,UEMURA M,et al.Recapitulating the human segmentation clock with pluripotent stem cells[J].Nature,2020,580(7801):124-129.
[57]	MATSUMIYA M,TOMITA T,YOSHIOKA-KOBAYASHI K,et al.ES cell-derived presomitic mesoderm-like tissues for analysis of synchronized oscillations in the segmentation clock[J].Development,2018,145(4):dev156836.
[58]	PALMEIRIM I,HENRIQUE D,ISH-HOROWICZ D,et al.Avian hairy gene expression identifies a molecular clock linked to vertebrate segmentation and somitogenesis[J].Cell,1997,91(5):639-648.
[59]	YOSHIOKA-KOBAYASHI K,KAGEYAMA R.Imaging and manipulating the segmentation clock[J].Cell Mol Life Sci,2021,78(4):1221-1231.
[60]	GOLDBETER A,GONZE D,POURQUIÉO.Sharp developmental thresholds defined through bistability by antagonistic gradients of retinoic acid and FGF signaling[J].Dev Dyn,2007,236(6):1495-1508.
[61]	MORIMOTO M,TAKAHASHI Y,ENDO M,et al.The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity[J].Nature,2005,435(7040):354-359.
[62]	DELFINI M C,DUBRULLE J,MALAPERT P,et al.Control of the segmentation process by graded MAPK/ERK activation in the chick embryo[J].Proc Natl Acad Sci U S A,2005,102(32):11343-11348.
[63]	MORENO T A,KINTNER C.Regulation of segmental patterning by retinoic acid signaling during Xenopus somitogenesis[J]. Dev Cell,2004,6(2):205-218.
[64]	KAGEYAMA R,SHIMOJO H,ISOMURA A.Oscillatory control of notch signaling in development[M]//BORGGREFE T,GIAIMO B D.Molecular Mechanisms of Notch Signaling.Cham:Springer,2018:265-277.
[65]	SPARROW D B,GUILLÉN-NAVARRO E,FATKIN D,et al.Mutation of HAIRY-AND-ENHANCER-OF-SPLIT-7 in humans causes spondylocostal dysostosis[J].Hum Mol Genet,2008,17(23):3761-3766.
[66]	HUBAUD A,POURQUIÉ O.Signalling dynamics in vertebrate segmentation[J].Nat Rev Mol Cell Biol,2014,15(11):709-721.
[67]	OATES A C,MORELLI L G,ARES S.Patterning embryos with oscillations:structure,function and dynamics of the vertebrate segmentation clock[J].Development,2012,139(4):625-639.
[68]	HUBAUD A,REGEV I,MAHADEVAN L,et al.Excitable dynamics and Yap-dependent mechanical cues drive the segmentation clock[J].Cell,2017,171(3):668-682.e1-e6.
[69]	BESSHO Y,SAKATA R,KOMATSU S,et al.Dynamic expression and essential functions of Hes7 in somite segmentation[J]. Genes Dev,2001,15(20):2642-2647.
[70]	NIWA Y,MASAMIZU Y,LIU T X,et al.The initiation and propagation of Hes7 oscillation are cooperatively regulated by Fgf and notch signaling in the somite segmentation clock[J].Dev Cell,2007,13(2):298-304.
[71]	BESSHO Y,HIRATA H,MASAMIZU Y,et al.Periodic repression by the bHLH factor Hes7 is an essential mechanism for the somite segmentation clock[J].Genes Dev,2003,17(12):1451-1456.
[72]	TAKASHIMA Y,OHTSUKA T,GONZÁLEZ A,et al.Intronic delay is essential for oscillatory expression in the segmentation clock[J].Proc Natl Acad Sci U S A,2011,108(8):3300-3305.
[73]	HIRATA H,BESSHO Y,KOKUBU H,et al.Instability of Hes7 protein is crucial for the somite segmentation clock[J].Nat Genet,2004,36(7):750-754.
[74]	SPARROW D B,CHAPMAN G,SMITH A J,et al.A mechanism for gene-environment interaction in the etiology of congenital scoliosis[J].Cell,2012,149(2):295-306.
[75]	HARIMA Y,TAKASHIMA Y,UEDA Y,et al.Accelerating the tempo of the segmentation clock by reducing the number of introns in the Hes7 gene[J].Cell Rep,2013,3(1):1-7.