Embryonic cell cycles

Embryonic cell cycles regulation at G2/M by patterning cues... 

In summary, transcription of the Cdc25-type phosphatase encoded by string limits the progression of many embryonic cell cycles, which are rapid (1—3 h) and require little cell growth. The massive ofi-regulatory region of string acts as a sophisticated pattern sensor that is influenced by a wide variety of cell type-specific transcription factors (Fig. 2A). 

The Xenopus system has proven instrumental in determining the mechanism controlling exit from mitosis at the metaphase/anaphase transition. Studies in this area have relied heavily on extracts prepared from fully mature oocytes/ unfertilized eggs that are arrested at metaphase of the second meiotic division. Upon Ca2+ addition, anaphase is initiated and the extract enters the first embryonic cell cycle to replicate DNA. The activity responsible for metaphase arrest was discovered by Masui at the same time as MPF (Masui Markert 1971), and given the name cytostatic factor (CSF). CSF has never been purified... 

Special control of the early embryonic cell cycles in the early mouse embryo... 

The results show that CSF activity fluctuates after oocyte activation. Inactivation of CSF proceeds in two steps first, CSF is transiently down-regulated by a mechanism independent from Mos degradation and MAP kinase inactivation to allow exit from the M II arrest. Second, the disappearance of CSF activity after the transition to the first embryonic cell cycle requires inactivation of the MAP kinase pathway. 

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. 

The entry into the first mitotic M phase at the end of the first embryonic cell cycle requires activation of MPF. In the mouse one-cell embryo this activation is fully autonomous from the nucleus (Ciemerych 1995, Ciemerych et al 1998). It proceeds within the cytoplasts obtained either by enucleation or by bisection of the embryo. Other autonomous phenomena are the cortical activity, or the deformation of the one-cell embryo, directly preceding the entry into first mitosis (Waksmundzka et al 1984) and the cyclic activity of K+ ion channels (Day et al 1998). The role of the cortical activity remains unknown however, the fact that it directly precedes the entry into the first mitotic M phase suggests that it could be linked to the activation... 

Do later embryonic cell cycles differ from the somatic ones ... 

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. 

A. W. Murray and M. W. Kirschner, Cyclin synthesis drives the early embryonic cell cycle. Nature 339, 275-280 (1989). 

Fig. 10.2. (a) The early amphibian embryonic cell cycle, (b) Role of maturation (or mitosis)-promoting factor (MPF) and cyclin in the periodic alternation of interphase and mitosis in that cycle, ((a) reproduced from Murray, 1989b (b) reproduced from Minshull et al, 1989). 

Murray, A.W. 1989b. Cyclin synthesis and degradation and the embryonic cell cycle. J. Cell Sci. Suppl. 12 65-76. 

Murakami MS, Vande Woude GF. 1998. Analysis of the early embryonic cell cycles of Xenopus regulation of cell cycle length by Xe-weel and Mos. Development 125(2) 237-248. 

Sakamoto I, Takahara K, Yamashita M, Iwao Y. 1998. Changes in cyclin B during oocyte maturation and early embryonic cell cycle in the newt, Cynops pyrrhogaster requirement of germinal vesicle for MPF activation. Dev Biol 195(l) 60-69. 

Kim SH, Li C, Mailer JL. 1999b. A maternal form of the phosphatase Cdc25A regulates early embryonic cell cycles in Xenopus laevis. Dev Biol 212(2) 381-391. 

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