Laboratory/Faculty

Laboratory of Molecular Genetics
Group of Developmental Cell Biology

ProfessorKeita Ohsumi
Cortical remodeling of frog eggs during fertilization and cleavage
LecturerMari Iwabuchi
Structure and function of totipotent nuclei of fertilized eggs
▶Laboratory HP
Japanese
Keita Ohsumi Professor
Lab members

Each individual animal, including us Homo sapiens, originates from a single cell, the fertilized egg. Fertilized animal eggs are highly specialized, exceptionally large cells. Perhaps most remarkably among higher eukaryotic cells, they are totipotent in the strict sense, i.e., they can give rise to every cell type in the adult organism. In addition, fertilized eggs possess a remarkably high capacity for cell division; they divide into two daughter cells at very short intervals, less than one hour in some animals. The cell divisions of fertilized eggs, termed cleavage, take place so often because cell growth is not taking place. The resulting rapid increase in the cell number during early embryonic development is prerequisite for subsequent cellular differentiation. We are interested in the remarkable features of fertilized animal eggs, particularly the high proliferative capacity of the eggs of amphibians. Fertilized eggs of the frog Xenopus laevis, for example, undergo cell divisions at intervals as short as 30 minutes. This means that the fertilized eggs and early embryonic cells of Xenopus replicate genomic DNA within 15 minutes and undergo cleavage very quickly. We seek to understand the basis for the remarkable potency of amphibian eggs at the molecular level. We are also interested in intercellular communication during the differentiation of germ cells in teleosts.

Molecular mechanisms for the high proliferative capacity of fertilized eggs

In the nucleus of fertilized Xenopus eggs, some of the chromatin and nuclear membrane proteins found in the adult have been substituted by variants specific to early embryonic cells. The expression of the specific variants in eggs is thought to relate to the unique regulation of nuclear functions, e.g., high replication and low transcription activities characteristic to early embryonic cells. It is also intriguing that in cleaving Xenopus embryos, surface structures and the organization of cortical cytoskeletal filaments change drastically just before each cleavage. These cortical changes presumably relate to the formation and contraction of the contractile ring that brings about the separation of daughter cells. Focusing on these unique variants of nuclear proteins and the dynamic changes in the cortex, we are trying to elucidate the molecular mechanisms that make the fertilized egg a totipotent and actively dividing cell. To perform biochemical and molecular biological analyses, we use a cell-free system of egg extracts in which early embryonic nuclei can be formed, and isolated egg cortices that provide sufficient amounts of cortical materials for biochemical study; both can be prepared because eggs are so large. We have found that the attachment of chromatin to the envelope is less tight in the nucleus of early embryonic cells than that in other somatic cells, and that some cortical proteins change both their localization to the cortex and their chemical modifications over the course of cell division.

Fig.1

An unfertilized egg of Xenopus laevis (left), and the same egg at 5 min after fertilization. In the fertilized egg, the pigmented cortex of the animal hemisphere is contracted because of dynamic cortical remodeling upon fertilization.

References

  1. Ohsumi, K. et al., Science, 262, 2033-2035, 1993.
  2. Iwabuchi, M. et al., EMBO J., 19, 4513-4523, 2000.
  3. Yamamoto, T. M. et al., Dev. Biol., 279, 345-355, 2005.
  4. Shintomi, K. et al., Proc. Natl. Acad. Sci. USA, 102, 8210-8215, 2005.
  5. Nishiyama, T. et al., Nature, 446, 1096-1099, 2007.
  6. Nishiyama, T. et al., Nature, 449, 341-345, 2007.

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