期刊
PANCREAS
卷 36, 期 1, 页码 1-9出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MPA.0b013r318148c8e6
关键词
INGAP; Reg proteins; pancreogenesis; neuroendocrine lineage; pancreatic transcription factors
Objective: Adult islet neogenesis is believed to recapitulate elements of pancreatic endocrine development. Identifying factors that regulate islet neogenesis-associated protein (INGAP) gene activity could provide links to pancreas development. Methods: Predicted transcriptional regulators of INGAP were screened in an INGAP-promoter-reporter assay. Based upon their temporal expression, the occurrence of INGAP-positive cells during pancreas embryonic development were studied. Results: Pancreatic transcription factors, PDX-1, Ngn3, NeuroD, and Isl-1, activated the INGAP promoter, but PAX4, PAX6, and Nkx2.2 did not. The INGAP-positive cells were present in the developing pancreatic bud of the mouse embryo. Emerging clusters of unorganized endocrine cells were INGAP positive. These cells coexpressed insulin or somatostatin, but glucagon-expressing cells remained distinct. The INGAP-positive cells were also detected in the maturing neonatal endocrine cells organized into islets. In direct contrast to the embryo, glucagon localized with most INGAP-positive cells in the postnatal endocrine cells. The INGAP-positive cells juxtaposed pancreatic duct cells. A subset of 5-bromo-2-deoxyuridine-positive/ INGAP-positive cells was detected in the neonatal pancreas. Conclusions: These data implicate INGAP and/or Reg family proteins in endocrine cell patterning during embryonic development and suggest that INGAP immunoreactivity is a key marker associated with early endocrine cells.
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