The Mouse Embryo

Ginsburg, M., Snow, M. H. L., and McLaren, A. (1990). Primordial germ cells in the mouse embryo during gastrulation. Development 110 521-528. 

Hogan, B., Costantini, F., and Lacy, E. (1986). Manipulating the Mouse Embryo. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY. 

Rawles, M. E. (1947). Origin of pigment cells from the neural crest in the mouse embryo. Physiol. Zool. 20 248-266. 

Serbedzija, G. N., Fraser, S. E., and Bronner-Fraser, M. (1990). Pathways of trunk neural crest cell migration in the mouse embryo as revealed by vital dye labelling. Development 108 605-612. 

The first cell cycle of the mouse embryo differs in many respects from the second and the following cell cycles. It is characterized by a long Gl phase that starts after the penetration of the spermatozoon or artificial activation of the oocyte. During this period the chromatin of the oocyte completes the second meiotic division and forms the female pronucleus. At the same time, in the fertilized egg, the highly condensed chromatin of the sperm nucleus decondenses and sperm-specific proteins, protamines, are replaced by histones. After the initial sperm chromatin... 

The very beginning of the first mitotic cell cycle of the mouse embryo seems to be controlled by the mechanisms characteristic for both meiotic and mitotic cell cycles. Active MAP kinase, its substrate p90rsk and the CSF activity itself could influence the cellular processes within the one-cell embryo. Indeed, we have observed that despite the entry into the interphase (as judged by the low activity of MPF) some proteins are actively phosphorylated as during the meiotic M phase (e.g. 35 kDa complex Howlett et al 1986, Szollosi et al 1993), the nuclei and the microtubule interphase network start to form only 1.5 hours after activation (Szollosi et al 1993). This delay in the phenomena characteristic for the interphase could be linked to the mixed meiotic/mitotic character of this early period. This delay probably allows the correct transformation of the sperm nucleus into the male pronucleus. In species like Xenopus or Drosophila the transitional period between the meiotic and the mitotic cell cycle control is probably much shorter since it is proportional to duration of the short first cell cycle of these rapidly cleaving embryos. Mammalian embryos are perhaps the most suitable to study this transition because of the exceptionally long first embryonic cell cycle. 

This suggests that cyclin A2 is not essential for the early embryonic cell cycles. Also D-type cyclins seem to be dispensable for the early mouse embryo cell cycle progression since embryonic stem (ES) cells do not express them at all before differentiation (Savatier et al 1996). We do not know, however, whether the D-type cyclins are also absent in the early embryo. These observations suggest that not only could the first cell cycles of the mouse embryo have specific modifications, but also further embryonic cell cycles are specifically modified as well. Mammalian embryonic cell cycles are probably modified often during development. Such studies could allow us to determine a profile of a minimal cell cycle in mammals which must, however, be much more complex than a simple S M phase embryonic cell cycle of amphibians or insects. 

Kubiak Indeed, but given that it is a checkpoint which is activated at that time, there must be a reason to activate this checkpoint delay in the first mitosis and not in the second one. Whatever the mechanism is, it is maternally determined and it is specific for this particular mitosis. This is the only mitosis that depends entirely on maternal genes in the mouse embryos, so we must look for a mechanism triggering a checkpoint delay. 

The first site of myelopoiesis75 in the mouse embryo is the fetal liver, where the common myeloid progenitor, the megakaryocyte-erythrocyte-restricted progenitors and granulocyte-monocyte restricted progenitors are present. Myelopoiesis occurs in the fetal liver in the same manner as in adult bone marrow.81 However, the proliferation capacity, colony forming activity and differentiation capacity is different between the fetal liver and adult bone marrow.81... 

Robin, C. and Dzierzak, E. Hematopoietic stem cell enrichment from the AGM region of the mouse embryo, Methods Mol. Med., 105, 257, 2005. 

Delassus, S. and Cumano, A. Circulation of hematopoietic progenitors in the mouse embryo, Immunity, 4, 97, 1996. 

Fig. 1. Dynamics of DNA methylation levels during mouse development. The methylation patterns of the oocyte and the rapidly demethylated after fertilization sperm create the combined methylation patterns in the early mouse zygote. During the first two to three cleavage divisions, the 5mC levels decrease further and stay low through the blastula stage. Post-implantation, the mouse embryo genome is methylated de novo the CpG islands remain mostly unmethylated. The primordial germ cells remain unmethylated. During gametogenesis specific parental (maternal or paternal) patterns of DNA methylation are established at imprinted loci (for further details see Refs. [13, 14]) (re-drawn from Ref [4]).

Nagy A, Gertsenstein M, Vintersten K et al (2003) Manipulating the mouse embryo—a laboratory manual. Cold Spring Harbor Laboratory Press, New York... 

The combined fertility and embryo-fetal development study is described as a two study design in the ICH S5(R2) guideline (1) and is anticipated for use in rodents (usually rat but also the mouse) embryo-fetal development must still be evaluated in a second, nonrodent, species. 

Schiestl. Cigarette smoke induces DNA deletions in the mouse embryo. Cancer Res 1998 58(12) 2633-2638. 

Visel, A., Thaller, C., and Eichele, G. (2004) GeneRaint.org an atlas of gene expression patterns in the mouse embryo Nucleic Acids R 32,D552-6. 

Systematic screen for novel genes required in pattern formation, organogenesis and differentiation processes of the mouse embryo... 

Yavarone MS, Shuey DL, Tamir H, et al. Serotonin and cardiac morphogenesis in the mouse embryo. Teratology 1993 47 573-584. 

Passey RJ, Williams E, Lichanska AM, Wells C, Hu S, Geczy CL, Little MH, Hume DA. 1999. A null mutation in the inflammation-associated S100 protein S100A8 causes early resorption of the mouse embryo. J Immunol 163(4) 2209-2216. 

Nau H, Bass R. 1981. Transfer of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to the mouse embryo and fetus. Toxicology 20 299-308. 

Lauder JM, Wilkie MB, Wu C, Singh S. Expression of 5-HT2A, 5-HT2B and 5-HT2C receptors in the mouse embryo. Int J Dev Neurosci 2000 18 653-662. 

C. Sirard, J. L. de la Pompa, A. Elia, A. Itie, C. Mirtsos, A. Cheung, et al. The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryo. Genes Dev, 2 (1), 107-119.1998. 

---