title: Pax6 Inactivation in the Adult Pancreas Reveals Ghrelin as Endocrine Cell Maturation Marker.
abstract: The transcription factor Pax6 is an important regulator of development and cell differentiation in various organs. Thus, Pax6 was shown to promote neural development in the cerebral cortex and spinal cord, and to control pancreatic endocrine cell genesis. However, the role of Pax6 in distinct endocrine cells of the adult pancreas has not been addressed. We report the conditional inactivation of Pax6 in insulin and glucagon producing cells of the adult mouse pancreas. In the absence of Pax6, beta- and alpha-cells lose their molecular maturation characteristics. Our findings provide strong evidence that Pax6 is responsible for the maturation of beta-, and alpha-cells, but not of delta-, and PP-cells. Moreover, lineage-tracing experiments demonstrate that Pax6-deficient beta- and alpha-cells are shunted towards ghrelin marked cells, sustaining the idea that ghrelin may represent a marker for endocrine cell maturation.
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Department of Molecular Developmental Biology, RG Molecular Cell Differentiation, Goettingen, Germany.
authors.forename: Zeeshan
authors.initials: Z
authors.lastname: Ahmad
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Department of Molecular Developmental Biology, RG Molecular Cell Differentiation, Goettingen, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Rafeeq
authors.affiliation: Université de Nice Sophia Antipolis, Nice, France.|Inserm U1091, IBV, Diabetes Genetics Team, Nice, France.|JDRF, New York, NY, United States of America.|Genome and Stem Cell Center, GENKOK, Erciyes University, Kayseri, Turkey.
authors.forename: Patrick
authors.initials: P
authors.lastname: Collombat
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Department of Molecular Developmental Biology, RG Molecular Cell Differentiation, Goettingen, Germany.|JDRF, New York, NY, United States of America.|University of Goettingen, Department of Clinical Neurophysiology, Goettingen, Germany.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Mansouri
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage / Q000187:drug effects / Q000235:genetics; D003433:Crosses, Genetic; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D054439:Ghrelin / Q000235:genetics* / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics* / Q000378:metabolism; D050418:Pancreatic Polypeptide-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D019864:Somatostatin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D005136:Eye Proteins; D054439:Ghrelin; D018398:Homeodomain Proteins; D007328:Insulin; D008164:Luminescent Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; C054562:yellow fluorescent protein, Bacteria; D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases