The Reg family member INGAP is a marker of endocrine patterning in the embryonic pancreas.
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.
Hamblet
Natasha S
NS
Department of Internal Medicine, The Strelitz Diabetes Institutes, Eastern Virginia Medical School, Norfolk, VA 23510, USA.
Shi
Wenjing
W
Vinik
Aaron I
AI
Taylor-Fishwick
David A
DA
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000494:pharmacology; D002454:Cell Differentiation; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000032:analysis; D060850:LIM-Homeodomain Proteins; D051379:Mice; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009687:Nuclear Proteins; D010179:Pancreas / Q000196:embryology*; D000073718:Pancreatitis-Associated Proteins; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D011506:Proteins / Q000032:analysis* / Q000235:genetics; D015534:Trans-Activators / Q000494:pharmacology; D014157:Transcription Factors
D051792:Basic Helix-Loop-Helix Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D007328:Insulin; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C000715631:NKX2-2 protein, human; C407737:Neurog3 protein, mouse; C000715627:Nkx2-2 protein, mouse; C000612141:REG3A protein, human; C490253:Reg3b protein, mouse; C063843:insulin gene enhancer binding protein Isl-1; C084010:pancreatic and duodenal homeobox 1 protein; C093564:Neurogenic differentiation factor 1