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We attempt to gain comprehensive understanding how the body forms during early development in vertebrates, using a combination of molecular biology and cell biology (Fig. 1), from the viewpoints of organo-morphogenesis, cell polarity, cell migration, cell differentiation and regulation of gene expression. This research will serve as the basis for post-genomic projects, research on animal evolution and diversity, and cancer biology.
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- Intercellular signals and mechanisms for cell migration during organogenesis
During early development, the initially simple embryo gradually assumes a complex form. In the developing embryo, the cells do not simply undergo differentiation, but they also move to distant parts of the body. We also see dynamic changes of a sheet of epithelial cells, resulting in the formation of a variety of tubular structures (Fig. 2). We are particularly interested in understanding how these dynamic behaviors of cells are related to the vascular patterning, neural crest migration, and formation of neural network (Fig. 3). We have recently discovered a novel phenomenon that a part of somitic cells dynamically move towards the dorsal aorta by chemoattractive signals. We are currently investigating the chemoattraction at the molecular level.
- Polarity and formation of epithelial cells
During embryonic development, the cells assume various shapes. The phenomenon called “epithelial-to-mesenchymal transition (EMT)” is involved not only in organogenesis but also in metastasis of cancers (Fig. 2). We are studying how EMT and epithelial polarity are regulated using experimental models we have originally developed.
- Roles of Maf transcription factors in cell differentiation and preservation of cell function
MafA, a member of Maf family transcription factors, regulates the expression of insulin gene in beta-cells of the pancreatic islets (Fig. 4). Disorder of this transcription regulatory system can lead to the onset of diabetes mellitus. Maf transcription factors also play important roles in other organs and in carcinogenesis. We are clarifying their function at the molecular level.
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- Wang, H., et al., Diabetologia, 50:348-358, 2007
- Aramata S, et al, Biochim. Biophys. Acta, 1730:41-6, 2005
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Fig. 1 We analyze the molecular mechanism for organogenesis during embryonic development, primarily using chicken embryos.
Fig. 2 In early developing embryos, individual cells show a variety of behaviors. Inadequate regulation of these behaviors would lead to malformation of organs or carcinogenesis in adults.
Fig. 3 We have recently discovered a new phenomenon of cell migration involved in the network formation of neural- and vascular systems.
Fig. 4 Maf transcription factors are involved in cell differentiation, proliferation and tumorigenesis through regulating expression of tissue-specific genes. We are attempting to clarify their molecular mechanism.
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