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Institute for Biogenesis Research
Research Description

Yusuke Marikawa

Yusuke Marikawa, Ph.D.---Assistant Professor

Phone:  (808) 692-1411
Fax:  (808) 692-1962----------Email:  marikawa@hawaii.edu

Biosciences Building 163A, Kaka’ako

Ph.D. Zoology, Kyoto University, Japan 1995

Developmental Biology

Role of Wnt/beta-Catenin Signaling in Germ Layer Formation, Molecular Mechanisms of Nuclear Reprogramming

How can a single cell known as a fertilized egg give rise to a complex architecture like our body?  The goal of our research program is to elucidate the mechanisms of cell differentiation and body plan formation in early mammalian embryos.  The following two projects are on-going:

(1) Role of Wnt/beta-catenin signaling in germ layer formation:  Soon after implantation, an apparently homogenous population of embryonic cells starts to diversify into three distinct tissues, called germ layers (ectoderm, mesoderm and endoderm).  This is the initial step in producing sophisticated body structures.  We hypothesize that the inter-cellular signal transduction machinery, Wnt/beta-catenin signaling, plays the central role in the formation of the three germ layers.  Our experimental approaches to test this hypothesis include the use of in vitro (e.g., multi-potent embryonic cell lines) as well as in vivo (e.g., transgenic mouse embryos) systems.
Gene Expression

Expression pattern of Brachyury (left) and Wnt3a (right) genes in the mouse embryo at mid-gestation stage, as detected by the whole-mount in situ hybridization technique. Both genes are required for the formation of the germ layers.
(2) Molecular mechanisms of nuclear reprogramming:  Embryos normally develop in an irreversible manner, that is, from an “undifferentiated or pluripotent state” toa “differentiated or committed state”.(Experimentally, however, the nucleus of fully differentiated adult body cells can be induced to execute a complete developmental program to recreate the whole body, which is also known as “cloning”.  While the experiment revealed the hidden potential of the adult cell nucleus, the chances of successful cloning is extremely low.  Our current hypothesis is that the epigenetic status of the adult cell nucleus, namely DNA methylation, interferes with the proper reactivation of embryonic genes.  We are examining the relationship between DNA methylation level and gene expression patterns, using both cell lines and normal as well as cloned embryos.

Selected Publications

  1. Alarcón, V.B. and Marikawa, Y. 2003.  Deviation of the Blastocyst Axis from the First Cleavage Plane Does Not Affect the Quality of Mouse Postimplantation Development.  Biology of Reproduction.  69:1208-1212. .pdf

  2. Alarcón, V.B. and Marikawa, Y. 2004. Molecular study of mouse peri-implantation development using the in vitro culture of aggregated inner cell mass. Molecular Reproduction and Development 67:83-90. .pdf

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  3. Marikawa, Y., Fujita, T.C. and Alarcón, V.B. 2004. An enhancer-trap lacZ transgene reveals a distinct expression pattern of the Kinesin family 26B in mouse embryos. Development Genes and Evolution 214:64-71. .pdf

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  4. Marikawa, Y., Fujita, T.C. and Alarcón, V.B. 2005. Heterogeneous DNA methylation status of the regulatory element of the mouse Oct4 gene in adult somatic cell population. Cloning and Stem Cells 7:8-16. .pdf

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  5. Alarcón, V.B. and Marikawa, Y. 2005.  Unbiased Contribution of the First Two Blastomeres to Mouse Blastocyst Development.   Molecular Reproduction and Development 72:254-361. .pdf

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  6. Yamazaki, Y., Low, E.W., Marikawa, Y., Iwahashi, K., Bartolomei, M.S., McCarrey, J. R., and Yanagimachi, R. 2006.  Adult Mice Cloned from Migrating Primordial Germ Cells.  Proceedings of the National Academy of Sciences, U.S.A., 102:11361-11366. .pdf

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  7. Yamazaki, Y., Fujita, T.C., Low, E.W., Alarcón, V.B., Yanagimachi, R. and Marikawa, Y. 2006. Gradual DNA demethylation of the Oct4 promoter in cloned mouse embryos. Molecular Reproduction and Development73:180-8. .pdf

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  8. Marikawa, Y. 2006. Wnt/beta-catenin signaling and body plan formation in mouse embryos. Seminars in Cell and Developmental Biology 17:175-184. .pdf

  9. Hiiragi T., Alarcón V.B., Fujimori T., Louvet-Vallée S., Maleszewski M., Marikawa Y., Maro B. and Solter D. 2006.  Where do we stand now? Mouse early embryo patterning meeting in Freiburg, Germany (2005). International Journal of Developmental Biology 50:581-588. .pdf

 

Dana Tamashiro

Dana Tamashiro, M.Sc.

Lab Manager