|Budget Amount *help
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1999: ¥5,000,000 (Direct Cost: ¥5,000,000)
The purpose of the present study was to carry out molecular biological, cell biological and experimental embryological research on the morphogenesis and epithelial cytodifferentiation of the digestive organs, necessary for the maintenance of life. In the present work, functional analyses of genes involved in the regionaolization of the digestive tract, genes involved in the morphogenesis of the stomach, growth factors, transcription factors and those related to the epithelial-mesenchymal interactions have been done.
To obtained genes involved in the regionalization, we cloned several genes which showed different expression patterns between the proventriculus (glandular stomach) and gizzard (muscular stomach), and it was shown that their products are important for the differentiation of the mesenchyme. Especially, the differentiation of smooth muscle which is drastically different between the proventriculus and gizzard, we cloned CFKBP/AMP gene related to the smooth muscle differentiation. The mechanism that leads to the formation of smooth muscle layer in the outermost layer of the tract was elucidated with SMAP gene expression as a marker. As for the morphogenesis and cytodifferentiation of the proventriculus, it was revealed that EGF, one of the famous growth factors, and sonic hedgehog produced by epithelial cells play important roles. Also, the specific expression of the embryonic chicken pepsinogen gene in the proventricular gland cells was shown to be regulated by sox and GATA transcription factors. Lastly, we identified BMP2 as an important mesenchymal factor in inducing the proventricular glands and ECPg expression, since its over-expression in the mesenchyme greatly enhances gland formation while over-expression of Noggin, an antagonist of BMP, completely inhibits it. In summary, we could identify many key genes working during the establishment of primitive gut through the formation of functional digestive organs.