Abstract
The successful development from a single-cell zygote into a complex multicellular organism requires precise coordination of multiple cell-fate decisions. The very first of these is lineage specification into the inner cell mass (ICM) and trophectoderm (TE) during mammalian preimplantation development. In mouse embryos, transcription factors (TFs) such as Oct4, Sox2, and Nanog are enriched in cells of ICM, which gives rise to the fetus and yolk sac. Conversely, TFs such as Cdx2 and Eomes become highly upregulated in TE, which contribute to the placenta. Here, we review the current understanding of key transcriptional control mechanisms and genes responsible for these distinct differences during the first cell lineage specification. In particular, we highlight recent insights gained through advances in genome manipulation, live imaging, single-cell transcriptomics, and loss-of-function studies.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Alarcon VB (2010) Cell polarity regulator PARD6B is essential for trophectoderm formation in the preimplantation mouse embryo. Biol Reprod 83:347–358. https://doi.org/10.1095/biolreprod.110.084400
Alder O, Lavial F, Helness A et al (2010) Ring1B and Suv39h1 delineate distinct chromatin states at bivalent genes during early mouse lineage commitment. Development 137:2483–2492. https://doi.org/10.1242/dev.048363
Anani S, Bhat S, Honma-Yamanaka N, Krawchuk D, Yamanaka Y (2014) Initiation of Hippo signaling is linked to polarity rather than to cell position in the pre-implantation mouse embryo. Development 141:2813–2824. https://doi.org/10.1242/dev.107276
Arnold SJ, Robertson EJ (2009) Making a commitment: cell lineage allocation and axis patterning in the early mouse embryo. Nat Rev Mol Cell Biol 10:91–103. https://doi.org/10.1038/nrm2618
Auman HJ, Nottoli T, Lakiza O, Winger Q, Donaldson S, Williams T (2002) Transcription factor AP-2gamma is essential in the extra-embryonic lineages for early postimplantation development. Development 129:2733–2747
Bernstein BE, Meissner A, Lander ES (2007) The mammalian epigenome. Cell 128:669–681. https://doi.org/10.1016/j.cell.2007.01.033
Biase FH, Cao X, Zhong S (2014) Cell fate inclination within 2-cell and 4-cell mouse embryos revealed by single-cell RNA sequencing. Genome Res 24:1787–1796. https://doi.org/10.1101/gr.177725.114
Bosher JM, Williams T, Hurst HC (1995) The developmentally regulated transcription factor AP-2 is involved in c-erbB-2 overexpression in human mammary carcinoma. Proc Natl Acad Sci USA 92:744–747
Burton A, Torres-Padilla ME (2014) Chromatin dynamics in the regulation of cell fate allocation during early embryogenesis. Nat Rev Mol Cell Biol 15:723–734. https://doi.org/10.1038/nrm3885
Burton A, Muller J, Tu S, Padilla-Longoria P, Guccione E, Torres-Padilla ME (2013) Single-cell profiling of epigenetic modifiers identifies PRDM14 as an inducer of cell fate in the mammalian embryo. Cell Rep 5:687–701. https://doi.org/10.1016/j.celrep.2013.09.044
Cao Z, Carey TS, Ganguly A, Wilson CA, Paul S, Knott JG (2015) Transcription factor AP-2gamma induces early Cdx2 expression and represses HIPPO signaling to specify the trophectoderm lineage. Development 142:1606–1615. https://doi.org/10.1242/dev.120238
Chazaud C, Yamanaka Y (2016) Lineage specification in the mouse preimplantation embryo. Development 143:1063–1074. https://doi.org/10.1242/dev.128314
Choi I, Carey TS, Wilson CA, Knott JG (2012) Transcription factor AP-2gamma is a core regulator of tight junction biogenesis and cavity formation during mouse early embryogenesis. Development 139:4623–4632. https://doi.org/10.1242/dev.086645
Clayton L, Hall A, Johnson MH (1999) A role for Rho-like GTPases in the polarisation of mouse eight-cell blastomeres. Dev Biol 205:322–331. https://doi.org/10.1006/dbio.1998.9117
Cockburn K, Rossant J (2010) Making the blastocyst: lessons from the mouse. J Clin Invest 120:995–1003. https://doi.org/10.1172/JCI41229
Cockburn K, Biechele S, Garner J, Rossant J (2013) The Hippo pathway member Nf2 is required for inner cell mass specification. Curr Biol 23:1195–1201. https://doi.org/10.1016/j.cub.2013.05.044
Cui W, Dai X, Marcho C, Han Z, Zhang K, Tremblay KD, Mager J (2016a) Towards functional annotation of the preimplantation transcriptome: an RNAi screen in mammalian embryos. Sci Rep 6:37396. https://doi.org/10.1038/srep37396
Cui W, Pizzollo J, Han Z, Marcho C, Zhang K, Mager J (2016b) Nop2 is required for mammalian preimplantation development. Mol Reprod Dev 83:124–131. https://doi.org/10.1002/mrd.22600
Dahl JA, Reiner AH, Klungland A, Wakayama T, Collas P (2010) Histone H3 lysine 27 methylation asymmetry on developmentally-regulated promoters distinguish the first two lineages in mouse preimplantation embryos. PLoS One 5:e9150. https://doi.org/10.1371/journal.pone.0009150
De Vries WN, Evsikov AV, Haac BE et al (2004) Maternal beta-catenin and E-cadherin in mouse development. Development 131:4435–4445. https://doi.org/10.1242/dev.01316
Erhardt S, Lyko F, Ainscough JF, Surani MA, Paro R (2003) Polycomb-group proteins are involved in silencing processes caused by a transgenic element from the murine imprinted H19/Igf2 region in Drosophila. Dev Genes Evol 213:336–344
Fierro-Gonzalez JC, White MD, Silva JC, Plachta N (2013) Cadherin-dependent filopodia control preimplantation embryo compaction. Nat Cell Biol 15:1424–1433. https://doi.org/10.1038/ncb2875
Fleming TP, Sheth B, Fesenko I (2001) Cell adhesion in the preimplantation mammalian embryo and its role in trophectoderm differentiation and blastocyst morphogenesis. Front Biosci 6:D1000–D1007
Goolam M, Scialdone A, Graham SJ et al (2016) Heterogeneity in Oct4 and Sox2 targets biases cell fate in 4-cell mouse embryos. Cell 165:61–74. https://doi.org/10.1016/j.cell.2016.01.047
Guo G, Huss M, Tong GQ, Wang C, Li Sun L, Clarke ND, Robson P (2010) Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst. Dev Cell 18:675–685. https://doi.org/10.1016/j.devcel.2010.02.012
Herrmann D, Dahl JA, Lucas-Hahn A, Collas P, Niemann H (2013) Histone modifications and mRNA expression in the inner cell mass and trophectoderm of bovine blastocysts. Epigenetics 8:281–289. https://doi.org/10.4161/epi.23899
Hiiragi T, Solter D (2004) First cleavage plane of the mouse egg is not predetermined but defined by the topology of the two apposing pronuclei. Nature 430:360–364. https://doi.org/10.1038/nature02595
Hiiragi T, Louvet-Vallee S, Solter D, Maro B (2006) Embryology: does prepatterning occur in the mouse egg? Nature 442:E3–4; discussion E4. https://doi.org/10.1038/nature04907
Hilger-Eversheim K, Moser M, Schorle H, Buettner R (2000) Regulatory roles of AP-2 transcription factors in vertebrate development, apoptosis and cell-cycle control. Gene 260:1–12
Hirate Y, Hirahara S, Inoue K et al (2013) Polarity-dependent distribution of angiomotin localizes Hippo signaling in preimplantation embryos. Curr Biol 23:1181–1194. https://doi.org/10.1016/j.cub.2013.05.014
Home P, Saha B, Ray S et al (2012) Altered subcellular localization of transcription factor TEAD4 regulates first mammalian cell lineage commitment. Proc Natl Acad Sci USA 109:7362–7367. https://doi.org/10.1073/pnas.1201595109
Houliston E, Pickering SJ, Maro B (1989) Alternative routes for the establishment of surface polarity during compaction of the mouse embryo. Dev Biol 134:342–350
Kamburov A, Stelzl U, Lehrach H, Herwig R (2013) The ConsensusPathDB interaction database: 2013 update. Nucleic Acids Res 41:D793–D800. https://doi.org/10.1093/nar/gks1055
Kaneko KJ, DePamphilis ML (2013) TEAD4 establishes the energy homeostasis essential for blastocoel formation. Development 140:3680–3690. https://doi.org/10.1242/dev.093799
Koch U, Lehal R, Radtke F (2013) Stem cells living with a Notch. Development 140:689–704. https://doi.org/10.1242/dev.080614
Kono K, Tamashiro DA, Alarcon VB (2014) Inhibition of RHO-ROCK signaling enhances ICM and suppresses TE characteristics through activation of Hippo signaling in the mouse blastocyst. Dev Biol 394:142–155. https://doi.org/10.1016/j.ydbio.2014.06.023
Korotkevich E, Niwayama R, Courtois A, Friese S, Berger N, Buchholz F, Hiiragi T (2017) The apical domain is required and sufficient for the first lineage segregation in the mouse embryo. Dev Cell 40:235–247, e237. https://doi.org/10.1016/j.devcel.2017.01.006
Kuckenberg P, Buhl S, Woynecki T et al (2010) The transcription factor TCFAP2C/AP-2gamma cooperates with CDX2 to maintain trophectoderm formation. Mol Cell Biol 30:3310–3320. https://doi.org/10.1128/MCB.01215-09
Latham KE, Solter D, Schultz RM (1991) Activation of a two-cell stage-specific gene following transfer of heterologous nuclei into enucleated mouse embryos. Mol Reprod Dev 30:182–186
Leung CY, Zhu M, Zernicka-Goetz M (2016) Polarity in cell-fate acquisition in the early mouse embryo. Curr Top Dev Biol 120:203–234. https://doi.org/10.1016/bs.ctdb.2016.04.008
Li L, Lu X, Dean J (2013) The maternal to zygotic transition in mammals. Mol Asp Med 34:919–938. https://doi.org/10.1016/j.mam.2013.01.003
Maitre JL, Niwayama R, Turlier H, Nedelec F, Hiiragi T (2015) Pulsatile cell-autonomous contractility drives compaction in the mouse embryo. Nat Cell Biol 17:849–855. https://doi.org/10.1038/ncb3185
Maitre JL, Turlier H, Illukkumbura R, Eismann B, Niwayama R, Nedelec F, Hiiragi T (2016) Asymmetric division of contractile domains couples cell positioning and fate specification. Nature 536:344–348. https://doi.org/10.1038/nature18958
Manzanares M, Rodriguez TA (2013) Development: Hippo signalling turns the embryo inside out. Curr Biol 23:R559–R561. https://doi.org/10.1016/j.cub.2013.05.064
Marcho C, Cui W, Mager J (2015) Epigenetic dynamics during preimplantation development. Reproduction 150:R109–R120. https://doi.org/10.1530/REP-15-0180
Marikawa Y, Alarcon VB (2009) Establishment of trophectoderm and inner cell mass lineages in the mouse embryo. Mol Reprod Dev 76:1019–1032. https://doi.org/10.1002/mrd.21057
Morris SA, Teo RT, Li H, Robson P, Glover DM, Zernicka-Goetz M (2010) Origin and formation of the first two distinct cell types of the inner cell mass in the mouse embryo. Proc Natl Acad Sci USA 107:6364–6369. https://doi.org/10.1073/pnas.0915063107
Nishioka N, Yamamoto S, Kiyonari H et al (2008) Tead4 is required for specification of trophectoderm in pre-implantation mouse embryos. Mech Dev 125:270–283. https://doi.org/10.1016/j.mod.2007.11.002
Nishioka N, Inoue K, Adachi K et al (2009) The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass. Dev Cell 16:398–410. https://doi.org/10.1016/j.devcel.2009.02.003
Paul S, Knott JG (2014) Epigenetic control of cell fate in mouse blastocysts: the role of covalent histone modifications and chromatin remodeling. Mol Reprod Dev 81:171–182. https://doi.org/10.1002/mrd.22219
Piras V, Tomita M, Selvarajoo K (2014) Transcriptome-wide variability in single embryonic development cells. Sci Rep 4:7137. https://doi.org/10.1038/srep07137
Plachta N, Bollenbach T, Pease S, Fraser SE, Pantazis P (2011) Oct4 kinetics predict cell lineage patterning in the early mammalian embryo. Nat Cell Biol 13:117–123. https://doi.org/10.1038/ncb2154
Plusa B, Hadjantonakis AK, Gray D et al (2005) The first cleavage of the mouse zygote predicts the blastocyst axis. Nature 434:391–395. https://doi.org/10.1038/nature03388
Ralston A, Cox BJ, Nishioka N et al (2010) Gata3 regulates trophoblast development downstream of Tead4 and in parallel to Cdx2. Development 137:395–403. https://doi.org/10.1242/dev.038828
Rayon T, Menchero S, Nieto A et al (2014) Notch and hippo converge on Cdx2 to specify the trophectoderm lineage in the mouse blastocyst. Dev Cell 30:410–422. https://doi.org/10.1016/j.devcel.2014.06.019
Rossant J, Tam PP (2009) Blastocyst lineage formation, early embryonic asymmetries and axis patterning in the mouse. Development 136:701–713. https://doi.org/10.1242/dev.017178
Rugg-Gunn PJ, Cox BJ, Ralston A, Rossant J (2010) Distinct histone modifications in stem cell lines and tissue lineages from the early mouse embryo. Proc Natl Acad Sci USA 107:10783–10790. https://doi.org/10.1073/pnas.0914507107
Saha B, Home P, Ray S et al (2013) EED and KDM6B coordinate the first mammalian cell lineage commitment to ensure embryo implantation. Mol Cell Biol 33:2691–2705. https://doi.org/10.1128/MCB.00069-13
Sakaue M, Ohta H, Kumaki Y et al (2010) DNA methylation is dispensable for the growth and survival of the extraembryonic lineages. Curr Biol 20:1452–1457. https://doi.org/10.1016/j.cub.2010.06.050
Samarage CR, White MD, Alvarez YD et al (2015) Cortical tension allocates the first inner cells of the mammalian embryo. Dev Cell 34:435–447. https://doi.org/10.1016/j.devcel.2015.07.004
Sarmento OF, Digilio LC, Wang Y, Perlin J, Herr JC, Allis CD, Coonrod SA (2004) Dynamic alterations of specific histone modifications during early murine development. J Cell Sci 117:4449–4459. https://doi.org/10.1242/jcs.01328
Sasaki H (2015) Position- and polarity-dependent Hippo signaling regulates cell fates in preimplantation mouse embryos. Semin Cell Dev Biol 47–48:80–87. https://doi.org/10.1016/j.semcdb.2015.05.003
Schultz RM (2002) The molecular foundations of the maternal to zygotic transition in the preimplantation embryo. Hum Reprod Update 8:323–331
Shi J, Chen Q, Li X et al (2015) Dynamic transcriptional symmetry-breaking in pre-implantation mammalian embryo development revealed by single-cell RNA-seq. Development 142:3468–3477. https://doi.org/10.1242/dev.123950
Souilhol C, Cormier S, Tanigaki K, Babinet C, Cohen-Tannoudji M (2006) RBP-Jkappa-dependent notch signaling is dispensable for mouse early embryonic development. Mol Cell Biol 26:4769–4774. https://doi.org/10.1128/MCB.00319-06
Stanton JL, Green DP (2001) Meta-analysis of gene expression in mouse preimplantation embryo development. Mol Hum Reprod 7:545–552
Strumpf D, Mao CA, Yamanaka Y, Ralston A, Chawengsaksophak K, Beck F, Rossant J (2005) Cdx2 is required for correct cell fate specification and differentiation of trophectoderm in the mouse blastocyst. Development 132:2093–2102. https://doi.org/10.1242/dev.01801
Torres-Padilla ME, Parfitt DE, Kouzarides T, Zernicka-Goetz M (2007) Histone arginine methylation regulates pluripotency in the early mouse embryo. Nature 445:214–218. https://doi.org/10.1038/nature05458
Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, Zhang Y (2006) Histone demethylation by a family of JmjC domain-containing proteins. Nature 439:811–816. https://doi.org/10.1038/nature04433
Tun T, Hamaguchi Y, Matsunami N, Furukawa T, Honjo T, Kawaichi M (1994) Recognition sequence of a highly conserved DNA binding protein RBP-J kappa. Nucleic Acids Res 22:965–971
VerMilyea MD, O’Neill LP, Turner BM (2009) Transcription-independent heritability of induced histone modifications in the mouse preimplantation embryo. PLoS One 4:e6086. https://doi.org/10.1371/journal.pone.0006086
Watanabe T, Biggins JS, Tannan NB, Srinivas S (2014) Limited predictive value of blastomere angle of division in trophectoderm and inner cell mass specification. Development 141:2279–2288. https://doi.org/10.1242/dev.103267
Werling U, Schorle H (2002) Transcription factor gene AP-2 gamma essential for early murine development. Mol Cell Biol 22:3149–3156
White MD, Angiolini JF, Alvarez YD et al (2016a) Long-lived binding of Sox2 to DNA predicts cell fate in the four-cell mouse embryo. Cell 165:75–87. https://doi.org/10.1016/j.cell.2016.02.032
White MD, Bissiere S, Alvarez YD, Plachta N (2016b) Mouse embryo compaction. Curr Top Dev Biol 120:235–258. https://doi.org/10.1016/bs.ctdb.2016.04.005
Wicklow E, Blij S, Frum T, Hirate Y, Lang RA, Sasaki H, Ralston A (2014) HIPPO pathway members restrict SOX2 to the inner cell mass where it promotes ICM fates in the mouse blastocyst. PLoS Genet 10:e1004618. https://doi.org/10.1371/journal.pgen.1004618
Yagi R, Kohn MJ, Karavanova I, Kaneko KJ, Vullhorst D, DePamphilis ML, Buonanno A (2007) Transcription factor TEAD4 specifies the trophectoderm lineage at the beginning of mammalian development. Development 134:3827–3836. https://doi.org/10.1242/dev.010223
Yamanaka Y, Ralston A, Stephenson RO, Rossant J (2006) Cell and molecular regulation of the mouse blastocyst. Dev Dyn 235:2301–2314. https://doi.org/10.1002/dvdy.20844
Yamanaka Y, Lanner F, Rossant J (2010) FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse blastocyst. Development 137:715–724. https://doi.org/10.1242/dev.043471
Yeap LS, Hayashi K, Surani MA (2009) ERG-associated protein with SET domain (ESET)-Oct4 interaction regulates pluripotency and represses the trophectoderm lineage. Epigenetics Chromatin 2:12. https://doi.org/10.1186/1756-8935-2-12
Yu FX, Guan KL (2013) The Hippo pathway: regulators and regulations. Genes Dev 27:355–371. https://doi.org/10.1101/gad.210773.112
Zernicka-Goetz M, Morris SA, Bruce AW (2009) Making a firm decision: multifaceted regulation of cell fate in the early mouse embryo. Nat Rev Genet 10:467–477. https://doi.org/10.1038/nrg2564
Zhang K, Dai X, Wallingford MC, Mager J (2013a) Depletion of Suds3 reveals an essential role in early lineage specification. Dev Biol 373:359–372. https://doi.org/10.1016/j.ydbio.2012.10.026
Zhang K, Haversat JM, Mager J (2013b) CTR9/PAF1c regulates molecular lineage identity, histone H3K36 trimethylation and genomic imprinting during preimplantation development. Dev Biol 383:15–27. https://doi.org/10.1016/j.ydbio.2013.09.005
Zheng Z, Li H, Zhang Q, Yang L, Qi H (2016) Unequal distribution of 16S mtrRNA at the 2-cell stage regulates cell lineage allocations in mouse embryos. Reproduction 151:351–367. https://doi.org/10.1530/REP-15-0301
Zhou LQ, Dean J (2015) Reprogramming the genome to totipotency in mouse embryos. Trends Cell Biol 25:82–91. https://doi.org/10.1016/j.tcb.2014.09.006
Acknowledgements
This work is supported in part by NIH HD078942 and HD083311 to JM. WC is supported in part by Lalor Foundation postdoctoral fellowship.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this chapter
Cite this chapter
Cui, W., Mager, J. (2018). Transcriptional Regulation and Genes Involved in First Lineage Specification During Preimplantation Development. In: Knott, J., Latham, K. (eds) Chromatin Regulation of Early Embryonic Lineage Specification. Advances in Anatomy, Embryology and Cell Biology, vol 229. Springer, Cham. https://doi.org/10.1007/978-3-319-63187-5_4
Download citation
DOI: https://doi.org/10.1007/978-3-319-63187-5_4
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-63186-8
Online ISBN: 978-3-319-63187-5
eBook Packages: MedicineMedicine (R0)