Ghrelin is a novel target of Pax4 in endocrine progenitors of the pancreas and duodenum.
Pax4-deficient mice have a severe gastrointestinal endocrine deficiency: they lack most pancreatic cells that produce insulin or somatostatin and various duodenal endocrine cell types. Remarkably, Pax4-deficient mice also have an overabundance of ghrelin-expressing cells in the pancreas and duodenum. Detailed analysis of the Pax4 nullizygous pancreas determined that the mutant islets are largely composed of a distinctive endocrine cell type that expresses ghrelin, glucagon, islet amyloid polypeptide (IAPP), and low levels of Pdx1. Lineage-tracing analysis revealed that most of these unique endocrine cells directly arose from Pax4-deficient progenitors. Previous in vitro work reported that Pax4 is a transcriptional repressor of islet amyloid polypeptide (IAPP) and glucagon. In this study, we expanded those results by showing that Pax4 is also a repressor of gherlin. Together, our data further support the notion that Pax4 activity is necessary to establish appropriate patterns of gene expression in endocrine progenitors of the digestive tract.
Wang
Qian
Q
Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Elghazi
Lynda
L
Martin
Sophie
S
Martins
Isabelle
I
Srinivasan
R Satish
RS
Geng
Xin
X
Sleeman
Mark
M
Collombat
Patrick
P
Houghton
Janet
J
Sosa-Pineda
Beatriz
B
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004386:Duodenum / Q000378:metabolism*; D054439:Ghrelin / Q000378:metabolism*; D005934:Glucagon / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D051761:Paired Box Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism*; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism
C469265:ARX protein, mouse; D054439:Ghrelin; D018398:Homeodomain Proteins; D051761:Paired Box Transcription Factors; C110218:Pax4 protein, mouse; D014157:Transcription Factors; D005934:Glucagon