Disappearance of centroacinar cells in the Notch ligand-deficient pancreas.
Notch signaling has been shown to contribute to murine pancreatic development at various stages. Delta-like 1 (Dll1) or Jagged1 (Jag1) are the Notch ligands that solely function to trigger this signaling during the pancreatic bud stage (~e9.5) or after birth, respectively. However, it has not been elucidated whether these Notch ligands are required at the later stage (e10.5-18.5) when the particular pancreas structures form. Here, we detected the dual expression of Dll1 and Jag1 in the epithelium after e10.5, which was restricted to the ductal cell lineage, including centroacinar cells expressing Sox9, CD133 and Hes1 but not the ductal cell markers Hnf1β and DBA, at e18.5. To evaluate the significance of the Notch ligands during this period, we established double-floxed mice of Dll1 and Jag1 genes with Ptf1a-Cre knock-in allele and examined the effects on development. The abrogation of both ligands but not a single one led to the loss of centroacinar cells, which was due to the decrease in cell proliferation and the increase in cell death, as well as to the reduction of Sox9. These results suggested that Dll1 and Jag1 function redundantly and are necessary to maintain the centroacinar cells as an environmental niche in the developing pancreas.
Department of Immunology and Research Center for Regenerative Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Japan.|Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Yasuhiro
Y
Nakano
Department of Immunology and Research Center for Regenerative Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Japan.|Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, 113-0033, Japan.
Naoko
N
Negishi
Department of Internal Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
Seiho
S
Gocho
Department of Internal Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
Tetsuya
T
Mine
Department of Immunology and Research Center for Regenerative Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Japan.
Yuri
Y
Sakurai
Department of Immunology and Research Center for Regenerative Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Japan.
Masaki
M
Yazawa
Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Japan.
Koichiro
K
Abe
Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, 113-0033, Japan.
Hideo
H
Yagita
Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, 113-0033, Japan.
Sonoko
S
Habu
Institute of Virus Research, Kyoto University, 53 Kawahara-cho, Kyoto, 606-8507, Japan.
Ryoichiro
R
Kageyama
Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Yoshiya
Y
Kawaguchi
Department of Immunology and Research Center for Regenerative Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Japan.
Katsuto
K
Hozumi
D061354:Acinar Cells / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002135:Calcium-Binding Proteins / Q000378:metabolism; D049109:Cell Proliferation; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D000072100:Jagged-1 Protein; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010179:Pancreas / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000378:metabolism*; D055758:SOX9 Transcription Factor / Q000378:metabolism; D000072099:Serrate-Jagged Proteins
D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008024:Ligands; D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D055758:SOX9 Transcription Factor; D000072099:Serrate-Jagged Proteins; C527933:Sox9 protein, mouse