Foxa2 Controls Pdx1 Gene Expression in Pancreatic β-Cells In Vivo
CS Lee, NJ Sund, MZ Vatamaniuk, FM Matschinsky… - Diabetes, 2002 - Am Diabetes Assoc
Diabetes, 2002•Am Diabetes Assoc
Differentiation of early foregut endoderm into pancreatic endocrine and exocrine cells
depends on a cascade of gene activation events controlled by various transcription factors.
Prior in vitro analysis has suggested that the forkhead/winged helix transcription factor
Foxa2 (formerly HNF-3β) is a major upstream regulator of Pdx1, a homeobox gene essential
for pancreatic development. Pdx1 is also essential for the maintenance of glucose
homeostasis, as its human orthologue, IPF-1, is mutated in a subset of patients with early …
depends on a cascade of gene activation events controlled by various transcription factors.
Prior in vitro analysis has suggested that the forkhead/winged helix transcription factor
Foxa2 (formerly HNF-3β) is a major upstream regulator of Pdx1, a homeobox gene essential
for pancreatic development. Pdx1 is also essential for the maintenance of glucose
homeostasis, as its human orthologue, IPF-1, is mutated in a subset of patients with early …
Differentiation of early foregut endoderm into pancreatic endocrine and exocrine cells depends on a cascade of gene activation events controlled by various transcription factors. Prior in vitro analysis has suggested that the forkhead/winged helix transcription factor Foxa2 (formerly HNF-3β) is a major upstream regulator of Pdx1, a homeobox gene essential for pancreatic development. Pdx1 is also essential for the maintenance of glucose homeostasis, as its human orthologue, IPF-1, is mutated in a subset of patients with early-onset type 2 diabetes (MODY4). To analyze the Foxa2/Pdx1 regulatory cascade during pancreatic β-cell differentiation, we used conditional gene ablation of Foxa2 in mice. We demonstrated that the deletion of Foxa2 in β-cell−specific knockout mice results in downregulation of Pdx1 mRNA and subsequent reduction of PDX-1 protein levels in islets. These data represent the first in vivo demonstration that Foxa2 acts upstream of Pdx1 in the differentiated β-cell.
Am Diabetes Assoc