Biopolym. Cell. 2003; 19(1):3-10.
The genetic control of mammalian early embryogenesis
1Vagyna I. N., 1Evsikov S. V., 1Solomko A. P.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680


The review focuses on the problems of genetic control of mammalian early development. The modern views on the processes of pre-implantation development and implantation of eutherian embryos are discussed.


[1] Johnson MH. The molecular and cellular basis of preimplantation mouse development. Biol Rev Camb Philos Soc. 1981;56(3):463-98.
[2] Magnuson T. Genetic abnormalities and early mammalian development. Development in Mammals. Ed. M. H. Johnson. Amsterdam, 1983. Vol. 5: 209-210.
[3] Magnuson T, Epstein CJ. Genetic control of very early mammalian development. Biol Rev Camb Philos Soc. 1981;56(3):369-408.
[4] Pratt HP, Bolton VN, Gudgeon KA. The legacy from the oocyte and its role in controlling early development of the mouse embryo. Ciba Found Symp. 1983;98:197-227.
[5] West JD, Green JF. The transition from oocyte-coded to embryo-coded glucose phosphate isomerase in the early mouse embryo. J Embryol Exp Morphol. 1983;78:127-40.
[6] McLaren A. Analysis of maternal effects on development in mammals. J Reprod Fertil. 1981;62(2):591-6.
[7] McLaren A. The embryo. Reproduction in Mammals. Cambridge, 1982. Vol. 2: 1-25.
[8] Wiley LM, Kidder GM, Watson AJ. Cell polarity and development of the first epithelium. BioEssays. 1990;12(2):67–73.
[9] Shuttz GA. Utilization of genetic information in the preimplanlation mouse embryo. Experimental approaches to mammalian embryonic development. Eds J. Rossant., R. A. Pedersen. Cambridge, 1986: 239-265.
[10] Telford NA, Watson AJ, Schultz GA. Transition from maternal to embryonic control in early mammalian development: A comparison of several species. Mol Reprod Dev. 1990;26(1):90–100.
[11] Magnuson T. Mutations and chromosomal abnormalities: How are they useful for studying genetic control of early mammalian development?. Experimental approaches to mammalian embryoiiic development. Eds J. Rossant, R, A. Pedersen. Cambridge, 1987: 437-474.
[12] Kidder GM, McLachlin JR. Timing of transcription and protein synthesis underlying morphogenesis in preimplantation mouse embryos. Dev Biol. 1985;112(2):265-75.
[13] Levy JB, Johnson MH, Goodall H, Maro B. The timing of compaction: control of a major developmental transition in mouse early embryogenesis. J Embryol Exp Morphol. 1986;95:213-37.
[14] Seshagiri PB, McKenzie DI, Bavister BD, Williamson JL, Aiken JM. Golden hamster embryonic genome activation occurs at the two-cell stage: Correlation with major developmental changes. Mol Reprod Dev. 1992;32(3):229–35.
[15] Taylor KD, Piko L. Expression of ribosomal protein genes in mouse oocytes and early embryos. Mol Reprod Dev. 1992;31(3):182–8.
[16] Barron DJ, Valdimarsson G, Paul DL, Kidder GM. Connexin32, a gap junction protein, is a persistent oogenetic product through preimplantation development of the mouse. Dev Genet. 1989;10(4):318-23.
[17] Brenner CA, Adler RR, Rappolee DA, Pedersen RA, Werb Z. Genes for extracellular-matrix-degrading metalloproteinases and their inhibitor, TIMP, are expressed during early mammalian development. Genes Dev. 1989;3(6):848-59.
[18] West JD, Flockhart JH. Genetic differences in glucose phosphate isomerase activity among mouse embryos. Development. 1989;107(3):465-72.
[19] Wiekowski M, Miranda M, DePamphilis ML. Regulation of gene expression in preimplantation mouse embryos: effects of the zygotic clock and the first mitosis on promoter and enhancer activities. Dev Biol. 1991;147(2):403-14.
[20] Yasuda GK, Schubiger G. Temporal regulation in the early embryo: is MBT too good to be true? Trends Genet. 1992;8(4):124-7.
[21] Valdimarsson G, Kidder GM. Temporal control of gap junction assembly in preimplantation mouse embryos. J Cell Sci. 1995;108 (Pt 4):1715-22.
[22] Latham KE, Garrels JI, Chang C, Solter D. Quantitative analysis of protein synthesis in mouse embryos. I. Extensive reprogramming at the one- and two-cell stages. Development. 1991;112(4):921-32.
[23] Levinson J, Goodfellow P, vadeboncoeur M, McDevitt H. Identification of stage-specific polypeptides synthesized during murine preimplantation development. Proc Natl Acad Sci U S A. 1978;75(7):3332-6.
[24] McLachlin JR, Kidder GM. Intercellular junctional coupling in preimplantation mouse embryos: effect of blocking transcription or translation. Dev Biol. 1986;117(1):146-55.
[25] Kidder GM. The genetic program for preimplantation development. Dev Genet. 1992;13(5):319-25.
[26] Watson AJ, Damsky CH, Kidder GM. Differentiation of an epithelium: factors affecting the polarized distribution of Na+,K(+)-ATPase in mouse trophectoderm. Dev Biol. 1990;141(1):104-14.
[27] Watson AJ, Pape C, Emanuel JR, Levenson R, Kidder GM. Expression of Na,K-ATPase alpha and beta subunit genes during preimplantation development of the mouse. Dev Genet. 1990;11(1):41-8.
[28] MacPhee DJ, Barr KJ, De Sousa PA, Todd SD, Kidder GM. Regulation of Na+,K(+)-ATPase alpha subunit gene expression during mouse preimplantation development. Dev Biol. 1994;162(1):259-66.
[29] Jones DH, Davies TC, Kidder GM. Embryonic expression of the putative gamma subunit of the sodium pump is required for acquisition of fluid transport capacity during mouse blastocyst development. J Cell Biol. 1997;139(6):1545-52.
[30] MacPhee DJ, Jones DH, Barr KJ, Betts DH, Watson AJ, Kidder GM. Differential involvement of Na(+),K(+)-ATPase isozymes in preimplantation development of the mouse. Dev Biol. 2000;222(2):486-98.
[31] Paria BC, Huet-Hudson YM, Dey SK. Blastocyst's state of activity determines the "window" of implantation in the receptive mouse uterus. Proc Natl Acad Sci U S A. 1993;90(21):10159-62.
[32] Tan J, Paria BC, Dey SK, Das SK. Differential uterine expression of estrogen and progesterone receptors correlates with uterine preparation for implantation and decidualization in the mouse. Endocrinology. 1999;140(11):5310-21.
[33] Das SK, Wang XN, Paria BC, Damm D, Abraham JA, Klagsbrun M, Andrews GK, Dey SK. Heparin-binding EGF-like growth factor gene is induced in the mouse uterus temporally by the blastocyst solely at the site of its apposition: a possible ligand for interaction with blastocyst EGF-receptor in implantation. Development. 1994;120(5):1071-83.
[34] Shen MM, Leder P. Leukemia inhibitory factor is expressed by the preimplantation uterus and selectively blocks primitive ectoderm formation in vitro. Proc Natl Acad Sci U S A. 1992;89(17):8240-4.
[35] Stewart CL, Kaspar P, Brunet LJ, Bhatt H, Gadi I, K?ntgen F, Abbondanzo SJ. Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor. Nature. 1992;359(6390):76-9.
[36] Auernhammer CJ, Melmed S. Leukemia-inhibitory factor-neuroimmune modulator of endocrine function. Endocr Rev. 2000;21(3):313-45.
[37] Luetteke NC, Qiu TH, Peiffer RL, Oliver P, Smithies O, Lee DC. TGF alpha deficiency results in hair follicle and eye abnormalities in targeted and waved-1 mice. Cell. 1993;73(2):263-78.
[38] Paria BC, Elenius K, Klagsbrun M, Dey SK. Heparin-binding EGF-like growth factor interacts with mouse blastocysts independently of ErbB1: a possible role for heparan sulfate proteoglycans and ErbB4 in blastocyst implantation. Development. 1999;126(9):1997-2005.
[39] Dardik A, Schultz RM. Blastocoel expansion in the preimplantation mouse embryo: stimulatory effect of TGF-alpha and EGF. Development. 1991;113(3):919-30.
[40] Cross JC, Werb Z, Fisher SJ. Implantation and the placenta: key pieces of the development puzzle. Science. 1994;266(5190):1508-18.
[41] Mead RA. Embryonic diapause in vertebrates. J Exp Zool. 1993;266(6):629-41. PubMed PMID: 10845095.
[42] Renfree MB, Shaw G. Diapause. Annu Rev Physiol. 2000;62:353-75.
[43] Weitlauf HM. Metabolic changes in the blastocysts of mice and rats during delayed implantation. J Reprod Fertil. 1974;39(1):213-24.
[44] Weitlauf HM. Changes in the rate of translation with reactivation of delayed implanting mouse embryos. J Exp Zool. 1985;236(3):309-12.
[45] Kaye PL. Preimplantation growth factor physiology. Rev Reprod. 1997;2(2):121-7.
[46] Sherman MI, Barlow PW. Deoxyribonucleic acid content in delayed mouse blastocysts. J Reprod Fertil. 1972;29(1):123-6.
[47] Vogel P. Occurrence and interpretation of delayed implantation in insectivores. J Reprod Fertil Suppl. 1981;29:51-60.
[48] Hambartsoumian E, Taupin JL, Moreau JF, Frydman R, Chaouat G. In-vivo administration of progesterone inhibits the secretion of endometrial leukaemia inhibitory factor in vitro. Mol Hum Reprod. 1998;4(11):1039-44.
[49] Rider V, McRae A, Heap RB, Feinstein A. Passive immunization against progesterone inhibits endometrial sensitization in pseudopregnant mice and has antifertility effects in pregnant mice which are reversible by steroid treatment. J Endocrinol. 1985;104(1):153-8.
[50] Kennedy TJ. Prostaglandins and the endometrial vascular permeability changes preceding blastocyst implantation and deciduaiization. Progr Reprod Biol. 1980; 7: 234-43.
[51] Warner CM, Tollefson CM. The effect of estradiol on RNA synthesis in preimplantation mouse embryos cultured in vitro. Biol Reprod. 1977;16(5):627-32.
[52] Weitlauf HM, Kiessling AA. Activation of 'delayed implanting' mouse embryos in vitro. J Reprod Fertil Suppl. 1981;29:191-202.
[53] Bitton-Casimiri V, Brun JL, Psychoyos A. Uptake and incorporation of (3H)uridine by normal or diapausing rat blastocysts after various periods of culture. J Reprod Fertil. 1976;46(2):447-8.
[54] Paria BC, Das SK, Andrews GK, Dey SK. Expression of the epidermal growth factor receptor gene is regulated in mouse blastocysts during delayed implantation. Proc Natl Acad Sci U S A. 1993;90(1):55-9. PubMed PMID: 9291585.
[55] Stewart CL, Cullinan EB. Preimplantation development of the mammalian embryo and its regulation by growth factors. Dev Genet. 1997;21(1):91-101.
[56] Weitlauf HM, Knisley KA. Changes in surface antigens on preimplantation mouse embryos. Biol Reprod. 1992;46(5):811-6.
[57] Papaioannou VE. Diapause of mouse blastocysts transferred to oviducts of immature mice. J Reprod Fertil. 1986;76(1):105-13.
[58] Papaioannou VE, Ebert KM. Development of fertilized embryos transferred to oviducts of immature mice. J Reprod Fertil. 1986;76(2):603-8.
[59] Ebert KM, Papaioannou VE. In vivo culture of embryos in the immature mouse oviduct. Theriogenology. 1989;31(2):299-308.
[60] Tsunoda Y, McLaren A. Effect of various procedures on the viability of mouse embryos containing half the normal number of blastomeres. J Reprod Fertil. 1983;69(1):315-22.
[61] Matsumoto K, Miyake M, Utsumi K, Iritani A. Production of identical twins by separating two-cell rat embryos. Gamete Res. 1989;22(3):257-63. PubMed PMID: 2707729.
[62] Hoppe PC, Whitten WK. Does X chromosome inactivation occur during mitosis of first cleavage? Nature. 1972;239(5374):520.
[63] Dyban AP, Sekirina GG. [Preimplantation development of monozygotic twins. Experiments on mouse embryos]. Ontogenez. 1981;12(2):130-9.
[64] O'brien MJ, Critser ES, First NL. Developmental potential of isolated blastomeres from early murine embryos. Theriogenology. 1984;22(5):601-7.
[65] Tarkowski AK, Wr?blewska J. Development of blastomeres of mouse eggs isolated at the 4- and 8-cell stage. J Embryol Exp Morphol. 1967;18(1):155-80.
[66] Fiser PS, Macpherson JW. Development of embryonic structures from isolated mouse blastomeres. Can J Anim Sci. 1976;56(1):33–6.
[67] Chesn? P, Colas G, Cogni? Y, Gu?rin Y, S?vellec C. Lamb production using superovulation, embryo bisection, and transfer. Theriogenology. 1987;27(5):751-7.
[68] Nagashima H, Katoh Y, Shibata K, Ogawa S. Production of normal piglets from microsurgically split morulae and blastocysts. Theriogenology. 1988;29(2):485-95.
[69] Willadsen SM. Micromanipulation of embryos of the large domestic species. Mammalian egg transfer. Ed CE. Adams. Florida, 1982: 185-210.
[70] Rands GF. Size regulation in the mouse embryo. II. The development of half embryos. J Embryol Exp Morphol. 1986;98:209-17.
[71] Evsikov SV, Vagyna IN, Solomko AP. Mechanisms of cell number regulation in the peri-implantation mouse blastocyst. J Exp Zool. 1996;276(3):201-8.