Spleen versus pancreas: strict control of organ interrelationship revealed by analyses of Bapx1−/− mice

  1. Amir Asayesh1,
  2. James Sharpe2,
  3. Robert P. Watson2,
  4. Jacob Hecksher-Sørensen2,4,
  5. Nicholas D. Hastie2,
  6. Robert E. Hill2,3, and
  7. Ulf Ahlgren1,3,5
  1. 1Umeå Centre for Molecular Medicine, Umeå University, S-901 87, Umeå, Sweden;
  2. 2MRC Human Genetics Unit, Western General Hospital, Edinburgh, EH4 2XU, United Kingdom

    Abstract

    During early stages of pancreatic development, the mesenchyme that contributes to the spleen overlies the dorsal pancreatic endoderm. Here, we show that interactions between splenic mesenchyme and pancreas proceed via a highly orchestrated morphogenetic program. Disruption of morphogenesis, as occurs in the Bapx1(Nkx3.2)−/− embryo, results in transformation of these tissues into well-organized, ectopic gut-like structures. Bapx1 plays a crucial organizing role effecting position and separation of the spleen and pancreas to prevent this metaplastic transformation. Similar transformations occur in organ cultures employing wild-type pancreatic endoderm and spleen mesenchyme, revealing the developmental plasticity of the pancreas and that precise spatial and temporal control of tissue interactions are required for development of both organs.

    Keywords

    Footnotes

    • 3 These authors contributed equally to this work.

    • 4 Present address: Hagedorn Research Institute, Niels Stensens Vej 6, DK-2820, Gentofte, Denmark.

    • 5 Corresponding author.

      5 E-MAIL ulf.ahlgren{at}ucmm.umu.se; FAX 46-90-785-4400.

    • Supplemental material is available at http://www.genesdev.org.

    • Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.381906.

      • Received February 1, 2006.
      • Accepted May 31, 2006.
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