The bHLH protein PTF1-p48 is essential for the formation of the exocrine and the correct spatial organization of the endocrine pancreas

  1. Andrea Krapp1,3,4,
  2. Martin Knöfler1,3,5,
  3. Birgit Ledermann2,
  4. Kurt Bürki2,
  5. Catherine Berney1,
  6. Nicole Zoerkler1,
  7. Otto Hagenbüchle1, and
  8. Peter K. Wellauer1,6
  1. 1Swiss Institute for Experimental Cancer Research, CH-1066 Epalinges, Switzerland; 2Embryonic Stem Cell Unit, Novartis, CH-4002 Basel, Switzerland

Abstract

We have generated a mouse bearing a null allele of the gene encoding basic helix–loop–helix (bHLH) protein p48, the cell-specific DNA-binding subunit of hetero-oligomeric transcription factor PTF1 that directs the expression of genes in the exocrine pancreas. The null mutation, which establishes a lethal condition shortly after birth, leads to a complete absence of exocrine pancreatic tissue and its specific products, indicating that p48 is required for differentiation and/or proliferation of the exocrine cell lineage. p48 is so far the only developmental regulator known to be required exclusively for committing cells to an exocrine fate. The hormone secreting cells of all four endocrine lineages are present in the mesentery that normally harbors the pancreatic organ until day 16 of gestation. Toward the end of embryonic life, cells expressing endocrine functions are no longer detected at their original location but are now found to colonize the spleen, where they persist in a functional state until postnatal death of the organism occurs. These findings suggest that the presence of the exocrine pancreas is required for the correct spatial assembly of the endocrine pancreas and that, in its absence, endocrine cells are directed by default to the spleen, a site that, in some reptiles, harbors part of this particular cellular compartment.

Keywords

Footnotes

  • 3 These authors contributed equally to this work.

  • Present addresses: 4Department of Microbiology and Genetics, Centre Médical Universitaire, University of Geneva, CH-1211 Genève 4, Switzerland; 5Department of Obstetrics and Gynecology, University of Vienna, A-1090 Vienna, Austria.

  • 6 Corresponding author.

  • E-MAIL Peter.Wellauer{at}isrec.unil.ch; FAX 41 21 652-6933.

    • Received June 4, 1998.
    • Accepted September 30, 1998.
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