2005 Fiscal Year Final Research Report Summary
Mechanisms of regulation of development of pancreatic beta cells by Notch signal for beta cell regeneration therapy
| Project/Area Number |
16590904
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | KYOTO UNIVERSIIY |
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Principal Investigator |
HOSODA Kiminori Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 講師 (40271598)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Hiroshi Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (40252457)
HAMADA Yoshio National Institute For Basic Biology, Research Associate, 培養育成研究施設, 助手 (10132739)
MASUZAKI Hiroaki Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (00291899)
HAYASHI Tatsuya Kyoto University, Graduate School of Human and Environmental Studies, Associate Professor, 人間・環境学研究科, 助教授 (00314211)
EBIHARA Ken Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (70362514)
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| Project Period (FY) |
2004 – 2005
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| Keywords | diabetes / pancreas / notch / RBP-J / beta cells |
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| Research Abstract |
To investigate the precise role of Notch/Rbp-j signaling in the pancreas, we inactivated Rbp-j by crossing Rbp-j foxed 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.
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