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Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells

Author

Listed:
  • Ulf Ahlgren

    (University of Umeå)

  • Samuel L. Pfaff

    (Columbia University
    The Salk Institute)

  • Thomas M. Jessell

    (Columbia University)

  • Thomas Edlund

    (University of Umeå)

  • Helena Edlund

    (University of Umeå)

Abstract

The mammalian pancreas is a specialized derivative of the primitive gut endoderm and controls many homeostatic functions through the activity of its component exocrine acinar and endocrine islet cells. The LIM homeodomain protein ISL1 is expressed in all classes of islet cells in the adult1,2 and its expression in the embryo is initiated soon after the islet cells have left the cell cycle. ISL1 is also expressed in mesenchymal cells that surround the dorsal but not ventral evagination of the gut endoderm, which together comprise the pancreatic anlagen. To define the role of ISL1 in the development of the pancreas, we have now analysed acinar and islet cell differentiation in mice deficient in ISL1 function3. Dorsal pancreatic mesenchyme does not form in ISL1-mutant embryos and there is an associated failure of exocrine cell differentiation in the dorsal but not the ventral pancreas. There is also a complete loss of differentiated islet cells. Exocrine, but not endocrine, cell differentiation in the dorsal pancreas can be rescued in vitro by provision of mesenchyme derived from wild-type embryos. These results indicate that ISL1, by virtue of its requirement for the formation of dorsal mesenchyme, is necessary for the development of the dorsal exocrine pancreas, and also that ISL1 function in pancreatic endodermal cells is required for the generation of all endocrine islet cells.

Suggested Citation

  • Ulf Ahlgren & Samuel L. Pfaff & Thomas M. Jessell & Thomas Edlund & Helena Edlund, 1997. "Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells," Nature, Nature, vol. 385(6613), pages 257-260, January.
  • Handle: RePEc:nat:nature:v:385:y:1997:i:6613:d:10.1038_385257a0
    DOI: 10.1038/385257a0
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    Cited by:

    1. Lu Han & Yongxia Wu & Kun Fang & Sean Sweeney & Ulyss K. Roesner & Melodie Parrish & Khushbu Patel & Tom Walter & Julia Piermattei & Anthony Trimboli & Julia Lefler & Cynthia D. Timmers & Xue-Zhong Yu, 2023. "The splanchnic mesenchyme is the tissue of origin for pancreatic fibroblasts during homeostasis and tumorigenesis," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Jia Q. Ng & Toghrul H. Jafarov & Christopher B. Little & Tongtong Wang & Abdullah M. Ali & Yan Ma & Georgette A. Radford & Laura Vrbanac & Mari Ichinose & Samuel Whittle & David J. Hunter & Tamsin R. , 2023. "Loss of Grem1-lineage chondrogenic progenitor cells causes osteoarthritis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Romana Bohuslavova & Valeria Fabriciova & Ondrej Smolik & Laura Lebrón-Mora & Pavel Abaffy & Sarka Benesova & Daniel Zucha & Lukas Valihrach & Zuzana Berkova & Frantisek Saudek & Gabriela Pavlinkova, 2023. "NEUROD1 reinforces endocrine cell fate acquisition in pancreatic development," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. Markus Draaken & Michael Knapp & Tracie Pennimpede & Johanna M Schmidt & Anne-Karolin Ebert & Wolfgang Rösch & Raimund Stein & Boris Utsch & Karin Hirsch & Thomas M Boemers & Elisabeth Mangold & Stefa, 2015. "Genome-wide Association Study and Meta-Analysis Identify ISL1 as Genome-wide Significant Susceptibility Gene for Bladder Exstrophy," PLOS Genetics, Public Library of Science, vol. 11(3), pages 1-13, March.

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