胚胎早期发育过程中主要信号通路的作用机制

doi:10.12280/gjszjk.20210213

摘要/Abstract

摘要：

胚胎发育始于受精卵,后者经过多次卵裂,胚胎的形态发生变化的同时,内部细胞也向不同谱系分化,为随后原肠胚的形成奠定基础。在胚胎早期发育过程中,多种信号通路参与了精细调控,如Hippo信号通路的差异性激活导致了滋养外胚层（trophectoderm,TE）和内细胞群（inner cell mass,ICM）的分化;成纤维细胞生长因子/细胞外信号调节激酶（fibroblast growth factor/extracellular signal-regulated kinase,FGF/ERK）信号通路使ICM进一步分化为原始内胚层（primitive endoderm,PE）和外胚层（epiblast,EPI）;骨形态发生蛋白（bone morphogenetic protein,BMP）信号通路及经典Wnt信号通路不仅与胚胎细胞的多能性相关,还在胚轴的建立中发挥重要作用;Notch信号通路和Nodal信号通路主要参与了胚胎左右不对称的形成等。综述胚胎发育早期的几条主要信号通路的作用,为深入了解胚胎早期发育及其调控提供参考。

关键词: 胚胎发育, 细胞谱系, 胚层, 信号传导, Wnt信号通路

Abstract:

Embryonic development begins from the zygote. After multiple cleavages, the embryonic morphology changed, and the internal cells differentiated into the different lineages that laid the foundation for the subsequent formation of gastrula. The various signal pathways participate in the fine regulation of early embryonic development. For example, the differential activation of Hippo signal pathway leads to the differentiation of trophectoderm (TE) and inner cell mass (ICM); fibroblast growth factor/extracellular signal-regulated kinase (FGF/ERK) signaling pathway further differentiated ICM into primitive endoderm (PE) and epiblast (EPI); bone morphogenetic protein (BMP) signaling pathway and classic Wnt signaling pathway are not only related to the pluripotent of embryonic cells, but also play an important role in the establishment of hypocotyls; Notch signaling pathway and Nodal signaling pathway are mainly involved in the formation of left-right asymmetry of embryos. Here we review the role and regulation mechanism of the main signal pathways in early embryonic development, so as to provide reference for the in-depth understanding of the process of early embryonic development and regulation.

Key words: Embryonic development, Cell lineage, Germ layers, Signal transduction, Wnt signaling pathway

陈然然, 宋殿荣. 胚胎早期发育过程中主要信号通路的作用机制[J]. 国际生殖健康/计划生育, 2021, 40(6): 481-485.

CHEN Ran-ran, SONG Dian-rong. The Major Signaling Pathways in Early Embryonic Development[J]. Journal of International Reproductive Health/Family Planning, 2021, 40(6): 481-485.

参考文献 36

[1]	Molè MA, Weberling A, Zernicka-Goetz M. Comparative analysis of human and mouse development: From zygote to pre-gastrulation[J]. Curr Top Dev Biol, 2020, 136:113-138. doi: 10.1016/bs.ctdb.2019.10.002. doi: 10.1016/bs.ctdb.2019.10.002
[2]	Frum T, Ralston A. Visualizing HIPPO Signaling Components in Mouse Early Embryonic Development[J]. Methods Mol Biol, 2019, 1893:335-352. doi: 10.1007/978-1-4939-8910-2_25. doi: 10.1007/978-1-4939-8910-2_25
[3]	Sasaki K, Kojitani N, Hirose H, et al. Shank2 Binds to aPKC and Controls Tight Junction Formation with Rap1 Signaling during Establishment of Epithelial Cell Polarity[J]. Cell Rep, 2020, 31(1):107407. doi: 10.1016/j.celrep.2020.02.088. doi: 10.1016/j.celrep.2020.02.088 URL
[4]	Nishioka N, Yamamoto S, Kiyonari H, et al. Tead4 is required for specification of trophectoderm in pre-implantation mouse embryos[J]. Mech Dev, 2008, 125(3/4):270-283. doi: 10.1016/j.mod.2007.11.002. doi: 10.1016/j.mod.2007.11.002 URL
[5]	Lorthongpanich C, Messerschmidt DM, Chan SW, et al. Temporal reduction of LATS kinases in the early preimplantation embryo prevents ICM lineage differentiation[J]. Genes Dev, 2013, 27(13):1441-1446. doi: 10.1101/gad.219618.113. doi: 10.1101/gad.219618.113 URL
[6]	Bassalert C, Valverde-Estrella L, Chazaud C. Primitive Endoderm Differentiation: From Specification to Epithelialization[J]. Curr Top Dev Biol, 2018, 128:81-104. doi: 10.1016/bs.ctdb.2017.12.001. doi: S0070-2153(17)30071-6 pmid: 29477172
[7]	Cang Z, Wang Y, Wang Q, et al. A multiscale model via single-cell transcriptomics reveals robust patterning mechanisms during early mammalian embryo development[J]. PLoS Comput Biol, 2021, 17(3):e1008571. doi: 10.1371/journal.pcbi.1008571. doi: 10.1371/journal.pcbi.1008571 URL
[8]	Deathridge J, Antolović V, Parsons M, et al. Live imaging of ERK signalling dynamics in differentiating mouse embryonic stem cells[J]. Development, 2019, 146(12):dev172940. doi: 10.1242/dev.172940. doi: 10.1242/dev.172940
[9]	Li YP, Duan FF, Zhao YT, et al. A TRIM71 binding long noncoding RNA Trincr1 represses FGF/ERK signaling in embryonic stem cells[J]. Nat Commun, 2019, 10(1):1368. doi: 10.1038/s41467-019-08911-w. doi: 10.1038/s41467-019-08911-w URL
[10]	Azami T, Bassalert C, Allègre N, et al. Regulation of the ERK signalling pathway in the developing mouse blastocyst[J]. Development, 2019, 146(14):dev177139. doi: 10.1242/dev.177139. doi: 10.1242/dev.177139
[11]	Molotkov A, Mazot P, Brewer JR, et al. Distinct Requirements for FGFR1 and FGFR2 in Primitive Endoderm Development and Exit from Pluripotency[J]. Dev Cell, 2017, 41(5):511-526.e4. doi: 10.1016/j.devcel.2017.05.004. doi: S1534-5807(17)30386-6 pmid: 28552557
[12]	Yamanaka Y, Lanner F, Rossant J. FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse blastocyst[J]. Development, 2010, 137(5):715-724. doi: 10.1242/dev.043471. doi: 10.1242/dev.043471 pmid: 20147376
[13]	De Belly H, Stubb A, Yanagida A, et al. Membrane Tension Gates ERK-Mediated Regulation of Pluripotent Cell Fate[J]. Cell Stem Cell, 2021, 28(2):273-284.e6. doi: 10.1016/j.stem.2020.10.018. doi: 10.1016/j.stem.2020.10.018 URL
[14]	Kunath T, Saba-El-Leil MK, Almousailleakh M, et al. FGF stimulation of the Erk1/2 signalling cascade triggers transition of pluripotent embryonic stem cells from self-renewal to lineage commitment[J]. Development, 2007, 134(16):2895-2902. doi: 10.1242/dev.02880. doi: 10.1242/dev.02880 pmid: 17660198
[15]	Sozen B, Demir N, Zernicka-Goetz M. BMP signalling is required for extra-embryonic ectoderm development during pre-to-post-implantation transition of the mouse embryo[J]. Dev Biol, 2021, 470:84-94. doi: 10.1016/j.ydbio.2020.11.005. doi: 10.1016/j.ydbio.2020.11.005 URL
[16]	Beppu H, Kawabata M, Hamamoto T, et al. BMP type II receptor is required for gastrulation and early development of mouse embryos[J]. Dev Biol, 2000, 221(1):249-258. doi: 10.1006/dbio.2000.9670. doi: 10.1006/dbio.2000.9670 pmid: 10772805
[17]	Suwinska A, Ciemerych MA. Factors regulating pluripotency and differentiation in early mammalian embryos and embryo-derived stem cells[J]. Vitam Horm, 2011, 87:1-37. doi: 10.1016/B978-0-12-386015-6.00022-6. doi: 10.1016/B978-0-12-386015-6.00022-6 pmid: 22127235
[18]	Rogers KW, ElGamacy M, Jordan BM, et al. Optogenetic investigation of BMP target gene expression diversity[J]. Elife, 2020, 9:e58641. doi: 10.7554/eLife.58641. doi: 10.7554/eLife.58641 URL
[19]	de Jaime-Soguero A, Abreu de Oliveira WA, Lluis F. The Pleiotropic Effects of the Canonical Wnt Pathway in Early Development and Pluripotency[J]. Genes(Basel), 2018, 9(2):93. doi: 10.3390/genes9020093. doi: 10.3390/genes9020093
[20]	Huelsken J, Vogel R, Brinkmann V, et al. Requirement for beta-catenin in anterior-posterior axis formation in mice[J]. J Cell Biol, 2000, 148(3):567-578. doi: 10.1083/jcb.148.3.567. doi: 10.1083/jcb.148.3.567 pmid: 10662781
[21]	Garabedian MV, Good MC. OptoLRP6 Illuminates Wnt Signaling in Early Embryo Development[J]. J Mol Biol, 2021, 433(18):167053. doi: 10.1016/j.jmb.2021.167053. doi: 10.1016/j.jmb.2021.167053 URL
[22]	Afouda BA, Nakamura Y, Shaw S, et al. Foxh1/Nodal Defines Context-Specific Direct Maternal Wnt/β-Catenin Target Gene Regulation in Early Development[J]. iScience, 2020, 23(7):101314. doi: 10.1016/j.isci.2020.101314. doi: S2589-0042(20)30501-0 pmid: 32650116
[23]	Zhu P, Xu X, Lin X. Both ciliary and non-ciliary functions of Foxj1a confer Wnt/β-catenin signaling in zebrafish left-right patterning[J]. Biol Open, 2015, 4(11):1376-1386. doi: 10.1242/bio.012088. doi: 10.1242/bio.012088 URL
[24]	Souilhol C, Cormier S, Tanigaki K, et al. RBP-Jkappa-dependent notch signaling is dispensable for mouse early embryonic development[J]. Mol Cell Biol, 2006, 26(13):4769-4774. doi: 10.1128/MCB.00319-06. doi: 10.1128/MCB.00319-06 pmid: 16782866
[25]	Cardano M, Diaferia GR, Conti L, et al. mSEL-1L deficiency affects vasculogenesis and neural stem cell lineage commitment[J]. J Cell Physiol, 2018, 233(4):3152-3163. doi: 10.1002/jcp.26153. doi: 10.1002/jcp.26153 pmid: 28816361
[26]	Wang Y, Lu P, Wu B, et al. NOTCH maintains developmental cardiac gene network through WNT5A[J]. J Mol Cell Cardiol, 2018, 125:98-105. doi: 10.1016/j.yjmcc.2018.10.014. doi: 10.1016/j.yjmcc.2018.10.014 URL
[27]	Menchero S, Rollan I, Lopez-Izquierdo A, et al. Transitions in cell potency during early mouse development are driven by Notch[J]. Elife, 2019, 8:e42930. doi: 10.7554/eLife.42930. doi: 10.7554/eLife.42930 URL
[28]	Roussel CJ, Roussel MR. A mathematical model of the biochemical network underlying left-right asymmetry establishment in mammals[J]. Biosystems, 2018, 173:281-297. doi: 10.1016/j.biosystems.2018.10.003. doi: 10.1016/j.biosystems.2018.10.003 URL
[29]	Zhang H, Chen S, Shang C, et al. Interplay between Lefty and Nodal signaling is essential for the organizer and axial formation in amphioxus embryos[J]. Dev Biol, 2019, 456(1):63-73. doi: 10.1016/j.ydbio.2019.08.006. doi: 10.1016/j.ydbio.2019.08.006 URL
[30]	Sekine R, Shibata T, Ebisuya M. Synthetic mammalian pattern formation driven by differential diffusivity of Nodal and Lefty[J]. Nat Commun, 2018, 9(1):5456. doi: 10.1038/s41467-018-07847-x. doi: 10.1038/s41467-018-07847-x pmid: 30575724
[31]	Wei S, Wang Q. Molecular regulation of Nodal signaling during mesendoderm formation[J]. Acta Biochim Biophys Sin (Shanghai), 2018, 50(1):74-81. doi: 10.1093/abbs/gmx128. doi: 10.1093/abbs/gmx128 URL
[32]	Liu Z, Woo S, Weiner OD. Nodal signaling has dual roles in fate specification and directed migration during germ layer segregation in zebrafish[J]. Development, 2018, 145(17):dev163535. doi: 10.1242/dev.163535. doi: 10.1242/dev.163535
[33]	Reich S, Kayastha P, Teegala S, et al. Tbx2 mediates dorsal patterning and germ layer suppression through inhibition of BMP/GDF and Activin/Nodal signaling[J]. BMC Mol Cell Biol, 2020, 21(1):39. doi: 10.1186/s12860-020-00282-1. doi: 10.1186/s12860-020-00282-1 URL
[34]	Vincent SD, Dunn NR, Hayashi S, et al. Cell fate decisions within the mouse organizer are governed by graded Nodal signals[J]. Genes Dev, 2003, 17(13):1646-1662. doi: 10.1101/gad.1100503. doi: 10.1101/gad.1100503 URL
[35]	Dunn NR, Vincent SD, Oxburgh L, et al. Combinatorial activities of Smad2 and Smad3 regulate mesoderm formation and patterning in the mouse embryo[J]. Development, 2004, 131(8):1717-1728. doi: 10.1242/dev.01072. doi: 10.1242/dev.01072 pmid: 15084457
[36]	Linneberg-Agerholm M, Wong YF, Romero Herrera JA, et al. Naïve human pluripotent stem cells respond to Wnt, Nodal and LIF signalling to produce expandable naïve extra-embryonic endoderm[J]. Development, 2019, 146(24):dev180620. doi: 10.1242/dev.180620. doi: 10.1242/dev.180620