2018 Fiscal Year Final Research Report
Molecular mechanism in the formation of the junction between different epithelia and in vitro recapitulation
| Project/Area Number |
26253069
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山田 泰広 京都大学, iPS細胞研究所, 教授 (70313872)
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| Research Collaborator |
Sankoda Nao
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| Project Period (FY) |
2014-04-01 – 2019-03-31
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| Keywords | 食道胃接合部 |
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| Outline of Final Research Achievements |
In this study, we dissected the molecular mechanism in the formation of esophago-gastric (EC) junction during organogenesis. We found that Sox2 and Gata4 are initially co-expressed in the progenitor epithelia then expressions of Sox2 and Gata4 gradually formed gradients in inverse direction across the EC junction. Meanwhile, Fgf2 was induced in the gastric mesenchyme and proximal epithelial cells expressed FgfR2, resulting in the restricted activation of ERK at the junction. Separately sorted Gata4-low, -mid and -high epithelial cells at E13.5 formed stratified squamous, pseudostratified and simple columnar organoid, respectively, by in vitro culture. Furthermore, Fgf2 treatment to Gata4-low cells inhibited the differentiation to stratified squamous epithelia and stimulated the differentiation to transitional epithelia correspond to the E-C junction. Thus, spatio-temporal patterning of epithelial and mesenchymal Sox2/Gata4/ Fgf2 is important for the construction of EC junction.
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| Free Research Field |
発生学
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| Academic Significance and Societal Importance of the Research Achievements |
食道―胃接合部や十二指腸Vater乳頭部、直腸歯状線、子宮頸部などの“異なる上皮の接点”は人体の複数の場所に存在し、腫瘍の発生母地になり得るという臨床上の共通した特性がある。
本研究では、これまで未解明であった発生期食道―胃接合部の形成機構／維持機構を明らかにした。まず、接合部形成位置を挟んでそれぞれの細胞運命を規定する転写因子が逆方向の濃度勾配を形成し、上皮―間質相互作用で一方の間質シグナルを誘導し、他方の上皮でその受容体を発現するという巧みな方法で、接合部に限局したシグナル活性化を来すことがわかった。他の“異なる上皮の接点”形成機構にも共通する可能性があり、今後の解明が待たれる。
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