title: Islet-1 is required for the maturation, proliferation, and survival of the endocrine pancreas.
abstract: OBJECTIVE
  The generation of mature cell types during pancreatic development depends on the expression of many regulatory and signaling proteins. In this study, we tested the hypothesis that the transcriptional regulator Islet-1 (Isl-1), whose expression is first detected in the mesenchyme and epithelium of the developing pancreas and is later restricted to mature islet cells, is involved in the terminal differentiation of islet cells and maintenance of islet mass.
  
  
  METHODS
  To investigate the role of Isl-1 in the pancreatic epithelium during the secondary transition, Isl-1 was conditionally and specifically deleted from embryonic day 13.5 onward using Cre/LoxP technology.
  
  
  RESULTS
  Isl-1-deficient endocrine precursors failed to mature into functional islet cells. The postnatal expansion of endocrine cell mass was impaired, and consequently Isl-1 deficient mice were diabetic. In addition, MafA, a potent regulator of the Insulin gene and beta-cell function, was identified as a direct transcriptional target of Isl-1.
  
  
  CONCLUSIONS
  These results demonstrate the requirement for Isl-1 in the maturation, proliferation, and survival of the second wave of hormone-producing islet cells.
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Aiping
authors.initials: A
authors.lastname: Du
authors.forename: Chad S
authors.initials: CS
authors.lastname: Hunter
authors.forename: Johanna
authors.initials: J
authors.lastname: Murray
authors.forename: Daniel
authors.initials: D
authors.lastname: Noble
authors.forename: Chen-Leng
authors.initials: CL
authors.lastname: Cai
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Evans
authors.forename: Roland
authors.initials: R
authors.lastname: Stein
authors.forename: Catherine Lee
authors.initials: CL
authors.lastname: May
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004742:Enhancer Elements, Genetic / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology; D005136:Eye Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D019426:Integrases / Q000235:genetics; D007515:Islets of Langerhans / Q000166:cytology / Q000196:embryology / Q000502:physiology; D060850:LIM-Homeodomain Proteins; D051473:Maf Transcription Factors, Large / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D007328:Insulin; D060850:LIM-Homeodomain Proteins; D051473:Maf Transcription Factors, Large; C485160:Mafa protein, mouse; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; C084010:pancreatic and duodenal homeobox 1 protein; C045073:Cre recombinase; D019426:Integrases