The Reg family member INGAP is a marker of endocrine patterning in the embryonic pancreas

Pancreas. 2008 Jan;36(1):1-9. doi: 10.1097/MPA.0b013r318148c8e6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / pharmacology
  • Cell Differentiation
  • Gene Expression Regulation, Developmental / drug effects
  • Homeobox Protein Nkx-2.2
  • Homeodomain Proteins / pharmacology
  • Humans
  • Insulin / analysis
  • LIM-Homeodomain Proteins
  • Mice
  • Nerve Tissue Proteins / pharmacology
  • Nuclear Proteins
  • Pancreas / embryology*
  • Pancreatitis-Associated Proteins
  • Promoter Regions, Genetic / drug effects
  • Promoter Regions, Genetic / genetics
  • Proteins / analysis*
  • Proteins / genetics
  • Trans-Activators / pharmacology
  • Transcription Factors

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Homeobox Protein Nkx-2.2
  • Homeodomain Proteins
  • Insulin
  • LIM-Homeodomain Proteins
  • NKX2-2 protein, human
  • Nerve Tissue Proteins
  • Neurog3 protein, mouse
  • Nkx2-2 protein, mouse
  • Nuclear Proteins
  • Pancreatitis-Associated Proteins
  • Proteins
  • REG3A protein, human
  • Reg3b protein, mouse
  • Trans-Activators
  • Transcription Factors
  • insulin gene enhancer binding protein Isl-1
  • pancreatic and duodenal homeobox 1 protein
  • Neurogenic differentiation factor 1