Research Overview

We are trying to understand the mechanisms behind the production of various cells and how the entire body is built up during the process from a single cell, to fertilized egg, to the adult body (normal development). To this end, we look at changes in the cellular level such as cell division, elongation, and migration, as well as the activation of supporting signals, gene expression, and the resulting changes in overall shape at various levels.

Our research is focused on the following themes:

1. Mechanisms of vertebrate gastrointestinal differentiation
2. Expression of foregut and liver marker genes in chick embryos

The digestive tract, a long tube connecting the mouth and anus, differentiates into various organs. As such, we want to answer the following questions:

1. How does the endoderm (gastrointestinal tract epithelium) form?
2. How is the tube formed?
3. What is the molecular mechanism that transform the gastrointestinal tract, which initially exists in a similar state throughout the body, into organs with completely distinct structures and functions?
4. How do the boundaries of digestive organs form?
5. How does the diversity of the digestive tract emerge?

We are studying the differentiation of the gastrointestinal tract from many angles. The digestive tract epithelium is the most regenerative tissue in the human body, dividing and regenerating daily. Because of this, we are also interested in understanding what embryonic genes play roles during regeneration, and how diseases affect gene expression.

Prospective graduate students can express their interest by communicating with us by email.

Current Projects

Analyzing the Mechanisms Behind the Formation of Mesoderm and Endoderm: The Basis for Generating Various Cell Types

Animal bodies are made up of a variety of cells, all of which arise from a single fertilized egg. One of the most crucial events early in this process is the formation of three cell types: ectoderm, mesoderm, and endoderm. These cell types then develop into different tissue and organs such as the nerves, muscles, and the gastrointestinal tract. Many researchers have been trying to elucidate the mechanisms by which the mesoderm and the endoderm are formed. Recent work have found that in many animals, the mesoderm and endoderm originate from a single cell type known as mesendodermal cells. However, the mechanism by which this single cell type differentiates into the two distinct cell types—mesoderm and endoderm— still remained unclear.

Our research group has been addressing this question using sea squirts (Ascidians), which are marine invertebrates. A sea squirts is a sea-dwelling organisms that attaches itself to rocks and other surfaces. It draws seawater from an inlet siphon on the lower left portion of its body, which it then to filters to take plankton and nutrients, and then expels the filtered water out through an outlet siphon on its upper left. Although it difficult to visualize from its shape, ascidians belong to the same phylum, Chordata, as humans, chickens, and fish. This unique animal possess many characteristics that make it an ideal model for studying the mechanisms underlying mesoderm and endoderm formation.

Through our research, we have found that the nuclei of mesendodermal cells migrate to the mesoderm-forming side of the cell. During migration, mRNA that codes for the Not transciption factor is then transcribed and stored in the nucleus. This mRNA is then passed on to the mesodermal cells during subsequent cell divisions. This protein translated from the mRNA is necessary for mesodermal differentiation and prevents the cells from developing into the endoderm. We additionally found the direction of nuclear migration to be determined by the protein PI3K, which is present in higher concentrations on the side that will become the mesoderm. Currently, we are looking at the roles of PI3K and Not in greater detail with the aim determine the mechanisms of mesoderm and endoderm fate determination from fertilization onward.

Staff Highlight

Dr. Kimiko Fukuda (福田　公子) Associate Professor	Dr. Naohito Takatori (高鳥　直士) Associate Professor
Email:
kokko[at]tmu.ac.jp	takatori-naohito1[at]tmu.ac.jp
Read more:
(TMU Faculty Profile (Japanese))	(Researchgate Profile) (ResearchMap Profile) (TMU Faculty Profile (Japanese))
Lab Information: Department Laboratory Page (English) (Japanese)

Recent Publications

1. Amniogenic somatopleure: a novel origin of multiple cell lineages contributing to the cardiovascular system 

    Asai, R., Haneda, Y., Seya, D., Arima, Y., Fukuda, K., Kurihara, Y., Miyagawa-Tomita, S., and Kurihara, H. 

    Scientific Reports, 7, 8955, Aug 2017

2. LNGFR+THY-1+ human pluripotent stem cell-derived neural crest-like cells have the potential to develop into mesenchymal stem cells

    Ouchi, T., Morikawa, S., Shibata, S., Fukuda, K., Okuno, H., Fujimura, T., Kuroda, T., Ohyama, M., Akamatsu, W., Nakagawa, T., 

    and Okano, H. Differentiation, 92(5): 270-280,  Dec 2016

3. Polarization of PI3K Activity Initiated by Ooplasmic Segregation Guides Nuclear Migration in the Mesendoderm 

    Naohito Takatori, Kouhei Oonuma, Hiroki Nishida, Hidetoshi Saiga. Developmental Cell, 35(3) 333-343, Nov 2015

4. Analysis of the Transcription Regulatory Mechanism of Otx During the Development of the Sensory Vesicle in Ciona intestinalis 

    Kouhei Oonuma, Dan Hirose, Naohito Takatori, Hidetoshi Saiga. Zoological Science, 31(9) 565-572, Sep 2014

5. Continuous expression of Otx in the anterior neural lineage is supported by different transcriptional regulatory mechanisms during the development of Halocynthia roretzi     

         Kouhei Oonuma, Dan Hirose, Naohito Takatori, Hidetoshi Saiga. Development Growth & Differentiation, 56(2) 189-198, 

    Feb 2014

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