Pdx-1 and Ptf1a concurrently determine fate specification of pancreatic multipotent progenitor cells

Dev Biol. 2008 Apr 1;316(1):74-86. doi: 10.1016/j.ydbio.2008.01.011. Epub 2008 Jan 26.


The pancreas is derived from a pool of multipotent progenitor cells (MPCs) that co-express Pdx-1 and Ptf1a. To more precisely define how the individual and combined loss of Pdx-1 and Ptf1a affects pancreatic MPC specification and differentiation we derived and studied mice bearing a novel Ptf1a(YFP) allele. While the expression of Pdx-1 and Ptf1a in pancreatic MPCs coincides between E9.5 and 12.5 the developmental phenotypes of Pdx-1 null and Pdx-1; Ptf1a double null mice are indistinguishable, and an early pancreatic bud is formed in both cases. This finding indicates that Pdx-1 is required in the foregut endoderm prior to Ptf1a for pancreatic MPC specification. We also found that Ptf1a is neither required for specification of Ngn3-positive endocrine progenitors nor differentiation of mature beta-cells. In the absence of Pdx-1 Ngn3-positive cells were not observed after E9.5. Thus, in contrast to the deletion of Ptf1a, the loss of Pdx-1 precludes the sustained Ngn3-based derivation of endocrine progenitors from pancreatic MPCs. Taken together, these studies indicate that Pdx-1 and Ptf1a have distinct but interdependent functions during pancreatic MPC specification.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / physiology
  • Cell Differentiation*
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • Homeodomain Proteins / analysis
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Islets of Langerhans / cytology
  • Islets of Langerhans / embryology
  • Islets of Langerhans / metabolism
  • Luminescent Proteins / analysis
  • Luminescent Proteins / genetics
  • Mice
  • Mice, Mutant Strains
  • Microscopy, Fluorescence
  • Multipotent Stem Cells / cytology*
  • Multipotent Stem Cells / metabolism
  • Nerve Tissue Proteins / physiology
  • Pancreas / cytology
  • Pancreas / embryology*
  • Pancreas / metabolism
  • Trans-Activators / analysis
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / analysis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Basic Helix-Loop-Helix Transcription Factors
  • Homeodomain Proteins
  • Luminescent Proteins
  • Nerve Tissue Proteins
  • Neurog3 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • pancreatic and duodenal homeobox 1 protein
  • transcription factor PTF1