Stage in which embryo compaction occurs |
8-cell |
32-cell |
(Lo and Gilula, 1979Lo CW, Gilula NB. Gap junctional communication in the preimplantation mouse embryo. Cell. 1979;18(2):399-409. http://dx.doi.org/10.1016/0092-8674(79)90059-X. PMid:498274. http://dx.doi.org/10.1016/0092-8674(79)9...
; Becker and Davies, 1995Becker DL, Davies CS. Role of gap junctions in the development of the preimplantation mouse embryo. Microsc Res Tech. 1995;31(5):364-74. http://dx.doi.org/10.1002/jemt.1070310506. PMid:8534898. http://dx.doi.org/10.1002/jemt.107031050...
; van Soom et al., 1997van Soom A, Boerjan ML, Bols PE, Vanroose G, Lein A, Coryn M, de Kruif A. Timing of compaction and inner cell allocation in bovine embryos produced in vivo after superovulation. Biol Reprod. 1997;57(5):1041-9. http://dx.doi.org/10.1095/biolreprod57.5.1041. PMid:9369168. http://dx.doi.org/10.1095/biolreprod57.5...
) |
Stage in which embryo cavitation occurs |
Between 16 and 32-cell |
Between 32 and 64-cell |
(van Soom et al., 1992van Soom A, van Vlaenderen I, Mahmoudzadeh AR, Deluyker H, de Kruif A. Compaction rate of in vitro fertilized bovine embryos related to the interval from insemination to first cleavage. Theriogenology. 1992;38(5):905-19. http://dx.doi.org/10.1016/0093-691X(92)90165-N. PMid:16727189. http://dx.doi.org/10.1016/0093-691X(92)9...
; van Soom et al., 1997van Soom A, Boerjan ML, Bols PE, Vanroose G, Lein A, Coryn M, de Kruif A. Timing of compaction and inner cell allocation in bovine embryos produced in vivo after superovulation. Biol Reprod. 1997;57(5):1041-9. http://dx.doi.org/10.1095/biolreprod57.5.1041. PMid:9369168. http://dx.doi.org/10.1095/biolreprod57.5...
; Kidder and Watson, 2005Kidder GM, Watson AJ. Roles of Na,K-ATPase in early development and trophectoderm differentiation. Semin Nephrol. 2005;25(5):352-5. http://dx.doi.org/10.1016/j.semnephrol.2005.03.011. PMid:16139691. http://dx.doi.org/10.1016/j.semnephrol.2...
) |
Is TEAD4 essential for TE formation? |
Yes |
No |
(Kaneko and Depamphilis, 2013Kaneko KJ, DePamphilis ML. TEAD4 establishes the energy homeostasis essential for blastocoel formation. Development. 2013;140(17):3680-90. http://dx.doi.org/10.1242/dev.093799. PMid:23903192. http://dx.doi.org/10.1242/dev.093799...
; Sakurai et al., 2017Sakurai N, Takahashi K, Emura N, Hashizume T, Sawai K. Effects of downregulating TEAD4 transcripts by RNA interference on early development of bovine embryos. J Reprod Dev. 2017;63(2):135-42. http://dx.doi.org/10.1262/jrd.2016-130. PMid:27941302. http://dx.doi.org/10.1262/jrd.2016-130...
) |
Does CDX2 have any function in epithelium integrity? |
Yes |
Yes |
(Strumpf et al., 2005Strumpf D, Mao CA, Yamanaka Y, Ralston A, Chawengsaksophak K, Beck F, Rossant J. Cdx2 is required for correct cell fate specification and differentiation of trophectoderm in the mouse blastocyst. Development. 2005;132(9):2093-102. http://dx.doi.org/10.1242/dev.01801. PMid:15788452. http://dx.doi.org/10.1242/dev.01801...
; Goissis and Cibelli, 2014bGoissis MD, Cibelli JB. Functional characterization of CDX2 during bovine preimplantation development in vitro. Mol Reprod Dev. 2014b;81(10):962-70. http://dx.doi.org/10.1002/mrd.22415. PMid:25251051. http://dx.doi.org/10.1002/mrd.22415...
) |
Does CDX2 delection impair TE or blastocyst formation? |
No |
No |
(Strumpf et al., 2005Strumpf D, Mao CA, Yamanaka Y, Ralston A, Chawengsaksophak K, Beck F, Rossant J. Cdx2 is required for correct cell fate specification and differentiation of trophectoderm in the mouse blastocyst. Development. 2005;132(9):2093-102. http://dx.doi.org/10.1242/dev.01801. PMid:15788452. http://dx.doi.org/10.1242/dev.01801...
; Wu et al., 2010Wu G, Gentile L, Fuchikami T, Sutter J, Psathaki K, Esteves TC, Araúzo-Bravo MJ, Ortmeier C, Verberk G, Abe K, Schöler HR. Initiation of trophectoderm lineage specification in mouse embryos is independent of Cdx2. Development. 2010;137(24):4159-69. http://dx.doi.org/10.1242/dev.056630. PMid:21098565. http://dx.doi.org/10.1242/dev.056630...
; Goissis and Cibelli, 2014bGoissis MD, Cibelli JB. Functional characterization of CDX2 during bovine preimplantation development in vitro. Mol Reprod Dev. 2014b;81(10):962-70. http://dx.doi.org/10.1002/mrd.22415. PMid:25251051. http://dx.doi.org/10.1002/mrd.22415...
) |
Where is OCT4 detected after first differentiation? |
In ICM cells |
In TE and ICM cells |
(Ralston and Rossant, 2005Ralston A, Rossant J. Genetic regulation of stem cell origins in the mouse embryo. Clin Genet. 2005;68(2):106-12. http://dx.doi.org/10.1111/j.1399-0004.2005.00478.x. PMid:15996204. http://dx.doi.org/10.1111/j.1399-0004.20...
; Strumpf et al., 2005Strumpf D, Mao CA, Yamanaka Y, Ralston A, Chawengsaksophak K, Beck F, Rossant J. Cdx2 is required for correct cell fate specification and differentiation of trophectoderm in the mouse blastocyst. Development. 2005;132(9):2093-102. http://dx.doi.org/10.1242/dev.01801. PMid:15788452. http://dx.doi.org/10.1242/dev.01801...
; Kuijk et al., 2008Kuijk EW, Du Puy L, van Tol HT, Oei CH, Haagsman HP, Colenbrander B, Roelen BA. Differences in early lineage segregation between mammals. Dev Dyn. 2008;237(4):918-27. http://dx.doi.org/10.1002/dvdy.21480. PMid:18330925. http://dx.doi.org/10.1002/dvdy.21480...
) |
Does CDX2 negatively regulate OCT4 transcription? |
Yes |
No |
(Berg et al., 2011Berg DK, Smith CS, Pearton DJ, Wells DN, Broadhurst R, Donnison M, Pfeffer PL. Trophectoderm lineage determination in cattle. Dev Cell. 2011;20(2):244-55. http://dx.doi.org/10.1016/j.devcel.2011.01.003. PMid:21316591. http://dx.doi.org/10.1016/j.devcel.2011....
; Goissis and Cibelli, 2014bGoissis MD, Cibelli JB. Functional characterization of CDX2 during bovine preimplantation development in vitro. Mol Reprod Dev. 2014b;81(10):962-70. http://dx.doi.org/10.1002/mrd.22415. PMid:25251051. http://dx.doi.org/10.1002/mrd.22415...
; Sakurai et al., 2017Sakurai N, Takahashi K, Emura N, Hashizume T, Sawai K. Effects of downregulating TEAD4 transcripts by RNA interference on early development of bovine embryos. J Reprod Dev. 2017;63(2):135-42. http://dx.doi.org/10.1262/jrd.2016-130. PMid:27941302. http://dx.doi.org/10.1262/jrd.2016-130...
) |
OCT4 knockout leads to TE differentiation |
Yes |
No (morula block) |
(Nichols et al., 1998Nichols J, Zevnik B, Anastassiadis K, Niwa H, Klewe-Nebenius D, Chambers I, Schöler H, Smith A. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell. 1998;95(3):379-91. http://dx.doi.org/10.1016/S0092-8674(00)81769-9. PMid:9814708. http://dx.doi.org/10.1016/S0092-8674(00)...
; Daigneault et al., 2018Daigneault BW, Rajput S, Smith GW, Ross PJ. Embryonic POU5F1 is required for expanded bovine blastocyst formation. Sci Rep. 2018;8(1):7753. http://dx.doi.org/10.1038/s41598-018-25964-x. PMid:29773834. http://dx.doi.org/10.1038/s41598-018-259...
) |
Do SOX2 and OCT4 establish a direct regulatory relationship ? |
Yes |
No |
(Goissis and Cibelli, 2014aGoissis MD, Cibelli JB. Functional characterization of SOX2 in bovine preimplantation embryos. Biol Reprod. 2014a;90(2):30. http://dx.doi.org/10.1095/biolreprod.113.111526. PMid:24389873. http://dx.doi.org/10.1095/biolreprod.113...
; Xie et al., 2010Xie D, Chen CC, Ptaszek LM, Xiao S, Cao X, Fang F, Ng HH, Lewin HA, Cowan C, Zhong S. Rewirable gene regulatory networks in the preimplantation embryonic development of three mammalian species. Genome Res. 2010;20(6):804-15. http://dx.doi.org/10.1101/gr.100594.109. PMid:20219939. http://dx.doi.org/10.1101/gr.100594.109...
) |
NANOG knockout in ICM differentiation |
Maintain initial GATA6 expression but impairs both EPI and PrE |
Reduces GATA6 expression and impairs epiblast differentiation |
(Frankenberg et al., 2011Frankenberg S, Gerbe F, Bessonnard S, Belville C, Pouchin P, Bardot O, Chazaud C. Primitive endoderm differentiates via a three-step mechanism involving Nanog and RTK signaling. Dev Cell. 2011;21(6):1005-13. http://dx.doi.org/10.1016/j.devcel.2011.10.019. PMid:22172669. http://dx.doi.org/10.1016/j.devcel.2011....
; Ortega et al., 2020Ortega MS, Kelleher AM, O’Neil E, Benne J, Cecil R, Spencer TE. NANOG is required to form the epiblast and maintain pluripotency in the bovine embryo. Mol Reprod Dev. 2020;87(1):152-60. http://dx.doi.org/10.1002/mrd.23304. PMid:31803983. http://dx.doi.org/10.1002/mrd.23304...
) |
Is FGF4 necessary for the maintenance of GATA6 expression in ICM? |
Yes |
Yes |
(Kuijk et al., 2012Kuijk EW, van Tol LTA, Van de Velde H, Wubbolts R, Welling M, Geijsen N, Roelen BAJ. The roles of FGF and MAP kinase signaling in the segregation of the epiblast and hypoblast cell lineages in bovine and human embryos. Development. 2012;139(5):871–82. http://dx.doi.org /10.1242/dev.071688. PMid: 22278923. http://dx.doi.org /10.1242/dev.071688...
; Kang et al., 2013Kang M, Piliszek A, Artus J, Hadjantonakis, AK. FGF4 is required for lineage restriction and salt-and-pepper distribution of primitive endoderm factors but not their initial expression in the mouse. Development. 2013;140(2): 267–79. http://dx.doi.org /10.1242/dev.084996. PMid: 23193166. http://dx.doi.org /10.1242/dev.084996...
) |
FGFR inhibition effects |
Eliminate GATA6 and increase NANOG+ cells in ICM |
Doesn't alter the distribution of NANOG or GATA6+ cells |
(Yamanaka et al., 2010Yamanaka Y, Lanner F, Rossant J. FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse blastocyst. Development. 2010;137(5):715-24. http://dx.doi.org/10.1242/dev.043471. PMid:20147376. http://dx.doi.org/10.1242/dev.043471...
; Kujik et al., 2012) |
MEK inhibition effects |
Eliminate GATA6+ and increase NANOG+ cells in ICM |
Reduce GATA6 and enhance NANOG+ cells in ICM |
(Yamanaka et al., 2010Yamanaka Y, Lanner F, Rossant J. FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse blastocyst. Development. 2010;137(5):715-24. http://dx.doi.org/10.1242/dev.043471. PMid:20147376. http://dx.doi.org/10.1242/dev.043471...
; Kujik et al., 2012; Canizo et al., 2019Canizo JR, Ynsaurralde Rivolta AE, Vazquez Echegaray C, Suvá M, Alberio V, Aller JF, Guberman AS, Salamone DF, Alberio RH, Alberio R. A dose-dependent response to MEK inhibition determines hypoblast fate in bovine embryos. BMC Dev Biol. 2019;19(1):13. http://dx.doi.org/10.1186/s12861-019-0193-9. PMid:31272387. http://dx.doi.org/10.1186/s12861-019-019...
) |
Types of FGFR identified in ICM |
Fgfr1 and Fgfr 2 |
Fgfr1 and Fgfr3. Possibly Fgfr 2 |
(Ozawa et al., 2013Ozawa M, Yang QE, Ealy AD. The expression of fibroblast growth factor receptors during early bovine conceptus development and pharmacological analysis of their actions on trophoblast growth in vitro. Reproduction. 2013;145(2):191-201. http://dx.doi.org/10.1530/REP-12-0220. PMid:23241344. http://dx.doi.org/10.1530/REP-12-0220...
; Akizawa et al., 2016Akizawa H, Nagatomo H, Odagiri H, Kohri N, Yamauchi N, Yanagawa Y, Nagano M, Takahashi M, Kawahara M. Conserved roles of fibroblast growth factor receptor 2 signaling in the regulation of inner cell mass development in bovine blastocysts. Mol Reprod Dev. 2016;83(6):516-25. http://dx.doi.org/10.1002/mrd.22646. PMid:27060901. http://dx.doi.org/10.1002/mrd.22646...
; Molotkov et al., 2017Molotkov A, Mazot P, Brewer JR, Cinalli RM, Soriano P. Distinct Requirements for FGFR1 and FGFR2 in Primitive Endoderm Development and Exit from Pluripotency. Dev Cell. 2017;41(5):511-526.e4. http://dx.doi.org/10.1016/j.devcel.2017.05.004. PMid:28552557. http://dx.doi.org/10.1016/j.devcel.2017....
; Negrón-Pérez and Hansen, 2018Negrón-Pérez VM, Hansen PJ. Role of yes-associated protein 1, angiomotin, and mitogen-activated kinase kinase 1/2 in development of the bovine blastocyst. Biol Reprod. 2018;98(2):170-83. http://dx.doi.org/10.1093/biolre/iox172. PMid:29228123. http://dx.doi.org/10.1093/biolre/iox172...
) |