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Research Subjects


  • Molecular mechanisms of craniofacial development and associated anomalies
  • Molecular and cellular biology of mammalian cranial neural crest cells
  • Proliferation and regeneration of terminally differentiated neurons and cardiomyocytes
  • Understanding skull vault development
  • Functional analysis of Rb and p300 in cell cycle control and tumorigenesis.
  • Mechanisms of cell growth and differentiation.
  • Development and improvement of new practical techniques for the manupulation of mammalian post-implantation embryos including whole embryo culture, in utero and ex utero surgery.

    Molecular mechanisms of craniofacial development and associated anomalies


    Recent publications:
    1. Tom Kouki, Hajime Imai, Kazushi Aoto, Kazuhiro Eto , Seiji Shioda, KosukeKawamura and Sakae Kikuyama: Developmental origin of the rat adenohypophysis prior to the formation of Rathke's pouch. Development, 128, 959-963, 2001.
    2. Aoki K., Nakahara Y., Yamada S. and Eto K.: Role of polysialic acid on outgrowth of rat olfactory receptor neurons. Mechanisms of Development, 85, 103-110, 1999.
    3. Ishiguro S.: Molecular cloning, expression of rat Msx-1 and Msx-2 during early embryogenesis and roles for mandibular chondrogenesis. Kokubyo Gakkai Zasshi - J. Stomatological Society 66:33-45, 1999. (in Japanese)
    4. Osumi N., Hirota A., Ohuchi H., Nakafuku M., Iimura T., Kuratani S., Fujiwara M., Noji S. and Eto K.: Pax-6 is involved in specification of the hindbrain motor neuron subtype. Development 124, 2961-2967, 1997.
    5. Osumi N., Ninomiya Y. and Eto K.: Craniofacial embryology in vitro. Int. J. Devel. Biol. 41, 187-194, 1997.

    Molecular and cellular biology of mammalian cranial neural crest cells

    Recent publications:
    1. Imai H., Iimura T., Ota M., and Eto K.: The Contribution of Cranial Neural Crest Cells and Foregut Endoderm to Tooth Initiation in Rat Embryos: The Application of Long-term Mandibular Culture. Jpn. J. Oral Biol., 41: 268-281. 1999 (in Japanese).
    2. Imai H., Osumi-Yamashita N, and Eto K : Contribution of foregut endoderm to tooth Initiation of mandibular Incisor In Rat embryos. European J. oral Science.106, 19-23, 1998.
    3. Osumi-Yamashita N., Kuratani S., Ninomiya Y., Aoki K., Iseki S., Chareonvit S., Doi H., Fujiwara M., Watanabe T. and Eto K.: Cranial anomaly of homozygous rSey rat is associated with a defect in the migration pathway of midbrain crest cells. Devel. Growth & Differ. 39, 53-67, 1997.
    4. Chareonvit S., Osumi N., Ikeda M., and Eto K.: Murine forebrain and midbrain crest cells generate different characteristic derivatives in vitro. Develop. Growth Differ., 39, 493-503, 1997.

    Proliferation and regeneration of terminally differentiated neurons and cardiomyocytes


    Recent publications:
    1. Tamamori-Adachi, M., Ono, Y., Nozato, T., Abe, S., Ikeda, M.A., Marumo, F., and Hiroe, M.: Cyclin A/cdk2 activation is involved in hypoxia-induced apoptosis in cardiomyocytes. Circ Res.
    2. Tamamori M., Ito H., Hiroe M., Terada Y., Marumo F., and Ikeda M.A.: Essential roles for G1 cyclin-dependent kinase activity in development of cardiomyocyte hypertrophy. Am. J. Phys. 275,2036-40, 1998.

    Understanding skull vault development


           The research aim is to understand how mammalian skull forms including its origin of tissue.
           Fibroblast growth factor receptors (FGFRs) and a transcription factor, TWIST are known to be involved in skull development. Mutations in these genes cause congenital malformation called craniosynostosis, premature closure of one or more of sutures in the skull. The suture is a growth centre of developing skull . We have been trying to elucidate the function of the genes in skull development. We have suggested that TWIST is involved in the maintenance of undifferentiated condition of midsutural mesenchyme and FGFRs signalling contributes to the balance between cell proliferation and differentiation of osteogenic cells. We are currently setting up a system with viral vectors to change gene expresion locally in vivo. This will provide us with alternative or supportive techniques of gene targetting to justify further our hypothesis.
           We have recently suggested that skull vault development requires interaction between cranial neural crest cells and cranial mesoderm. We are planning to investigate molaecular mechanisms of the interaction.

    Recent publications:
    1. Jiang X., Iseki S, . Maxson R.E., Sucov H.M. and Morriss-Kay G.M.: Tissue origins and interactions in the mammalian skull vault. Dev. Biol., 241, 106-116, 2002.
    2. iseki S., Morriss-Kay G.M. and Eto K.: Study of Fibroblast Growth Factor Receptor Signalling during Skull Vault Development by Ex-Utero Surgery. J . Hard Tissue Biology, 10, 25-29, 2001.
    3. Johnson D, Iseki S, Wilkie AOM, Morriss-Kay GM.: Expression patterns of Twist and Fgfr1, -2 and -3 in the developing mouse coronal suture suggest a key role for Twist in suture initiation and biogenesis. Mech. Dev., 91, 341-345, 2000.
    4. Iseki S., Wilkie A.O.M. and Morriss-Kay G.M.: Fgfr1 and fgfr2 have distinct differentiation- and proliferation-related roles in the developing mouse skull vault. Development, 126, 5611-20, 1999.
    5. Iseki S., Wilkie A.O.M., Heath J.K., Ishimaru T., Eto K. and Morriss-Kay G.M.: Fgfr2 and osteopontin domians in the developing skull vault are mutually exclusive and can be altered by locally applied FGF2. Development, 124, 3375-3384, 1997.


    Functional analysis of Rb and p300 in cell cycle control and tumorigenesis


    Recent publications:
    1. Ohshima, T., Suganuma, T., and Ikeda, M.A.: A novel mutation lacking the bromodomain of the transcriptional co-activator p300 in the SiHa cervical carcinoma cell line. Biochem. Biophys. Res. Commun
    2. Ota M., Eto K., Ninomiya Y., and Ikeda M.A.: Accumulation of p300 mediates transcriptional repression of simian virus 40 enhancer in undifferentiated F9 embryonal carcinoma cells. Cell Growth. Diff., 9, 989-997. 1998.

    Mechanisms of cell growth and differentiation


    Recent publications:
    1. Ninomiya Y., Adams R., Morris-Kay G.M. and Eto K.: Apoptotic cell death in neuronal differentiation of P19 EC cells: Cell death follows reentry into S phase. J. Cell. Phys., 172, 25-35, 1997.
    2. Iimura T., Takeda K., Goseki M., Maruoka Y., Sasaki S. and Oida S.: Characterization of two length cDNA for human MSX-2 from dental pulp-derived cells. DNA Sequence.8:87-92, 1997.