title: Notch/Rbp-j signaling prevents premature endocrine and ductal cell differentiation in the pancreas.
abstract: To investigate the precise role of Notch/Rbp-j signaling in the pancreas, we inactivated Rbp-j by crossing Rbp-j floxed mice with Pdx.cre or Rip.cre transgenic mice. The loss of Rbp-j at the initial stage of pancreatic development induced accelerated alpha and PP cell differentiation and a concomitant decrease in the number of Neurogenin3 (Ngn3)-positive cells at E11.5. Then at E15, elongated tubular structures expressing ductal cell markers were evident; however, differentiation of acinar and all types of endocrine cells were reduced. During later embryonic stages, compensatory acinar cell differentiation was observed. The resultant mice exhibited insulin-deficient diabetes with both endocrine and exocrine pancreatic hypoplasia. In contrast, the loss of Rbp-j specifically in beta cells did not affect beta cell number and function. Thus, our analyses indicate that Notch/Rbp-j signaling prevents premature differentiation of pancreatic progenitor cells into endocrine and ductal cells during early development of the pancreas.
authors.affiliation: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Fujikura
authors.forename: Kiminori
authors.initials: K
authors.lastname: Hosoda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwakura
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tomita
authors.forename: Michio
authors.initials: M
authors.lastname: Noguchi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Masuzaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Tanigaki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yabe
authors.forename: Tasuku
authors.initials: T
authors.lastname: Honjo
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007328:Insulin / Q000172:deficiency; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010183:Pancreatic Ducts / Q000166:cytology / Q000196:embryology* / Q000378:metabolism* / Q000473:pathology; D051880:Receptors, Notch / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells
chemical_list: D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D007328:Insulin; C497571:Rbpj protein, mouse; D051880:Receptors, Notch