Department of Cell Biology

Members

Director	Naoki Mochizuki
Laboratory chiefs	Satoru Yamazaki, Hiroyuki Nakajima
Staff Scientist	Hajime Fukui, Haruko Takano, Keisuke Sako
Postdoctoral Fellow	Ayano Chiba, Hinako Kidokoro, Yuki Wakayama, Keiko Shimamoto, Li-Kun Phng
Graduate Student	Takahiro Miyazaki, Hiroko Takahama, Miki Imazu, Hiroki Fukuda, Athanasius Wrin Hudoyo, Mari Sakamoto, Hiroyuki Ishikawa, Hideki Yasutake

Goal of our research

We aim at exploring the molecular mechanism by which blood vessel formation and cardiogenesis are regulated during development.

Both cardiac progenitors and vascular progenitors originate from lateral plate mesoderm. The commitment of progenitor cells to the mature cardiomyocytes or endothelial cells are thought to be genetically programmed. The details of this program has not been clearly demonstrated, although the requirement of several transcription factors are reported. Therefore, we consider that we need to know how cardiovascular development is precisely regulated (Figure).

Understanding of the development of cardiovascular system contributes to developing new strategy for cardiovascular regeneration. Currently we have used zebrafish to investigate the cardiovascular development because this creature has great advantages:(1) quick development (2) extra-embryonic development (3) translucent and (4) easy gene manipulation. The embryos expressing fluorescent proteins under the cardiovascular-specific promoters can be visualized while they develop.

1.Research on blood vessel formation

Blood vessel formation starts from budding or branching from plexus. Then, budding endothelial cells extend from the central toward the peripheral. The extension of the blood vessels regulated by Rho family GTPases is followed by the lumen formation according to the intracellular polarity. To become maturated blood vessels, lumenized vessels might be pruned if they are not needed and might be associated with pericytes/smooth muscle cells. We have tried to develop the transgenic zebrafish allowing us to visualize the steps described above. The blood vessel formation can be visualized in the zebrafish in which fluorescence or probes are expressed using endothelial cell-specific promoter (Video 1).

1-a Visualizing Rho family GTPases in the developing blodd vessels
1-b Visualizing the interaction between blood vessels and neurons
1-c Visualizing the polarity of endothelial cell in the intersomitic vessels
1-d Visualizing authophagy and apoptosis
1-e Understanding how the VE-cadherin-dependent cell-cell contacts are established in the cultured cells

2.Research on cardiogenesis

Mature cardiomyocytesloose the ability of proliferation. Therefore, once the myocardium is damaged by ischemia, the damaged myocardium is replaced by fibrotic tissues. The heart failure is ascribed to the reduced contraction or relaxation due to the replacement of cardiomyocytes with unfavorable fibrosis.

To regenerate the damaged heart, most researchers have planned the myocardial cells derived from stem cells (ES cells, iPS cells, and residential cardiac progenitor cells). We aim at searching an alternative that enables us to increase the number of cardiomyocytes in the damaged heart. To this end, we have tried to understand how cardiogenesis is regulated to induce the proliferation of cardiomyocytes. We have developed the transgenic fish in which cardiomyocyte are visualized during cardiogenesis. (Video 2: cardiomyocytes (red), endocardium (green))

2-a Developing the zebrafish enables us to visualize cell cycle
2-b Developing those in which fluorescent proteins can be photoconverted to trace the fate of cardiomyocytes