Molecular mechanisms of development of the stem cell niche regulating intestinal epithelial dedifferentiation

2014 Fiscal Year Final Research Report

• Project/Area Number: 24570078
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphology/Structure
• Research Institution: Nippon Medical School
• Principal Investigator: ISHIZUYA-OKA Atsuko 日本医科大学, 医学部, 教授 (50175254)
• Co-Investigator(Renkei-kenkyūsha): HASEBE Takashi 日本医科大学, 医学部, 准教授 (70329027)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 小腸 / 幹細胞 / 上皮脱分化 / 甲状腺ホルモン / 変態 / アフリカツメガエル / ニッチ / シグナル伝達経路

Outline of Final Research Achievements

In the amphibian digestive tract, some of larval epithelial cells dedifferentiate into adult stem cells by the inductive action of thyroid hormone (TH). In the present study, to clarify molecular mechanisms underlying the epithelial dedifferentiation into the stem cells, we performed expression and functional analyses of TH response genes, using the culture system for the Xenopus laevis small intestine. Our results indicate that TH-activated Wnt5a/Ror2 signaling is essential for the larval epithelial dedifferentiation accompanied by changes in cell morphology. In addition, our findings strongly suggest that absorptive epithelial cells expressing Ror2, which are scattered in the larval epithelium, can dedifferentiate into the stem cells. To clarify the origin of the stem cells, we isolated the promoter of Ror2 and started to generate transgenic frogs for lineage analysis of the epithelial cells expressing Ror2.

Free Research Field

発生生物学