Rbp-j regulates expansion of pancreatic epithelial cells and their differentiation into exocrine cells during mouse development.
Notch signaling regulates cell fate determination in various tissues. We have reported the generation of mice with a pancreas-specific knockout of Rbp-j using Pdx.cre mice. Those mice exhibited premature endocrine and ductal differentiation. We now generated mice in which the Rbp-j gene was inactivated in Ptf1a-expressing cells using Ptf1a.cre mice. The timing of the Cre-mediated deletion in Rbp-j(f/f) Ptf1a.cre mice is 1 day later than that in Rbp-j(f/f) Pdx.cre mice. In Rbp-j(f/f) Ptf1a.cre mouse pancreases, at E13.5, the reduced Hes1 expression was accompanied by reduced epithelial growth, but premature endocrine cell differentiation was minimal. At E15.5, Pdx1 expression was repressed and acinar cell differentiation was reduced, but an increase in acinar cell proliferation was observed during the perinatal period. Our study indicates that, in addition to its role in preventing premature differentiation of early endocrine cells, Rbp-j regulates epithelial growth, Pdx1 expression, and acinar cell differentiation during mid-pancreatic development.
Fujikura
Junji
J
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan.
Hosoda
Kiminori
K
Kawaguchi
Yoshiya
Y
Noguchi
Michio
M
Iwakura
Hiroshi
H
Odori
Shinji
S
Mori
Eisaku
E
Tomita
Tsutomu
T
Hirata
Masakazu
M
Ebihara
Ken
K
Masuzaki
Hiroaki
H
Fukuda
Akihisa
A
Furuyama
Kenichiro
K
Tanigaki
Kenji
K
Yabe
Daisuke
D
Nakao
Kazuwa
K
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D051379:Mice; D018345:Mice, Knockout; D010179:Pancreas / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D046790:Pancreas, Exocrine / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D018398:Homeodomain Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497571:Rbpj protein, mouse; D051880:Receptors, Notch; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein