Laboratory of Molecular Genetics

Group of Developmental Cell Biology

Faculty and Research Theme

Keita Ohsumi Professor

Keita Ohsumi (Professor)

Cortical remodeling of frog eggs during fertilization and cleavage

Mari Iwabuchi (Associate Professor)

Structure and function of totipotent nuclei of fertilized eggs

Akira Kanamori (Assistant Professor)

Molecular mechanisms of sex differentiation

Fig. 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.

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.

Gonadal sex differentiation in teleosts
We are studying sexual differentiation of vertebrate gonads, paying particular attention to germ cell differentiation and interactions between germ and somatic cells in gonads.  Teleost fish are suitable for this research because their germ cells can undergo complete sexual differentiation into sperms or eggs irrespective of their genetic sex. We have chosen medaka as our main experimental fish, because both genetics and reverse genetics are applicable, and their male determining gene has already been identified. We also use a small hermaphrodite fish, Kryptolebias marmoratus, which is the only known self-fertilizing vertebrate.  Its gonad is an “ovotestis” in which small testicular tissue is localized in the dorsal side of the ovary.  For more details and references, please see http://www.bio.nagoya-u.ac.jp/gcoe/english/member/kanamori.html.
Lab members
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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Group of Biological Rhythm

Group of Developmental Cell Biology

Group of Plant Reproductive Systems

Group of Intracellular Dynamics

Group of Plant Developmental Biology

Group of Animal Development

Group of Brain Function and Structure

Group of Molecular Neurobiology

Group of Cell Regulation

Group of Molecular and Cell Biology

Group of Supra-molecular Structure

Group of Biomembrane Functions

Group of Developmental Morphogenesis

Group of Signal Transduction

Group of Plant Physiology

Group of Cell Biology

Group of Marine Developmental Biochemistry

Laboratory of Gene Analysis

Group of Functional Genomics and Clock Bio-nanomachine

Group of Animal Organ Functions

Group of Biochemistry

Unit on Nervous Development Systems

Unit of Cellular Morphogenesis

Group of Protein NMR Research