|Budget Amount *help
¥2,500,000 (Direct Cost : ¥2,500,000)
Fiscal Year 1997 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1996 : ¥1,500,000 (Direct Cost : ¥1,500,000)
During early development in vertebrate, tissues constituting the midline structures play important plays for subsequent morphogenesis. I previously found that the neural tube and its overlying surface ectoderm interact each other. It was shown by the fact that an ectopically transplanted neural tube induced expression of a homeobox gene, Msx 2, in the surface ectoderm at the graft site. The aim of this research project was to unveil the molecular mechanisms by which these interactions are regulated.
1. Molecular nature of interactions acting between the neural tube and the skin.
I found that BMP-4, a member of TGFbeta family, which is expressed in the dorsal portion of the neural tube acts on the overlying skin to cause it to express Msx 2. COS cells which had been transfected with BMP-4 cDNA were implanted into an ectopic region and this manipulation induced Msx 2 expression at the implantation site.
2.Role of BMP-4 in the ventral region.
In addition to the roles of BMP-4 in the neural tube, I also found that BMP-4 appears to have some roles in the formation of the ventral region of the body. When a high concentration of BMP-4 was administered into the dorsal mesoderm, this region was completely converted to the ventral mesoderm. It was revealed by using various molecular markers. Moreover, these effects were concentration-dependent.
From these results, BMP-4 appears to play roles not only at the dorsal midline but also in the morphogenesis of the ventral tissues of the body. Interestingly, both tissues are located far from the notochord. Therefore, it is conceivable that factors emanating form the notochord counteract with BMP-4, and that these counteractions control complex morphogenesis.