2021年7月
Essential role of Notch/Hes1 signaling in postnatal pancreatic exocrine development.
Journal of gastroenterology
- 巻
- 56
- 号
- 7
- 開始ページ
- 673
- 終了ページ
- 687
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1007/s00535-021-01779-y
BACKGROUND: Notch/Hes1 signaling has been shown to play a role in determining the fate of pancreatic progenitor cells. However, its function in postnatal pancreatic maturation is not fully elucidated. METHODS: We generated conditional Hes1 knockout and/or Notch intracellular domain (NICD) overexpression mice in Ptf1a- or Pdx1-positive pancreatic progenitor cells and analyzed pancreatic tissues. RESULTS: Both Ptf1acre/+; Hes1f/f and Ptf1acre/+; Rosa26NICD mice showed normal pancreatic development at P0. However, exocrine tissue of the pancreatic tail in Ptf1acre/+; Hes1f/f mice atrophied and was replaced by fat tissue by 4 weeks of age, with increased apoptotic cells and fewer centroacinar cells. This impaired exocrine development was completely rescued by NICD overexpression in Ptf1acre/+; Hes1f/f; Rosa26NICD mice, suggesting compensation by a Notch signaling pathway other than Hes1. Conversely, Pdx1-Cre; Hes1f/f mice showed impaired postnatal exocrine development in both the pancreatic head and tail, revealing that the timing and distribution of embryonic Hes1 expression affects postnatal exocrine tissue development. CONCLUSIONS: Notch signaling has an essential role in pancreatic progenitor cells for the postnatal maturation of exocrine tissue, partly through the formation of centroacinar cells.
- リンク情報
- ID情報
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- DOI : 10.1007/s00535-021-01779-y
- PubMed ID : 34128109