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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Karlsson, O., Thor, S., Norberg, T., Ohlsson, H. & Edlund, T. Nature 344, 879–882 (1990).
Thor, S., Ericson, J., Brännström, T. & Edlund, T. Neuron 7, 881–889 (1991).
Pfaff, S. L., Mendelsohn, M., Stewart, C. L., Edlund, T. & Jessell, T. M. cell 84, 309–320 (1996).
Way, J. C. & Chalfie, M. Cell 54, 5–16 (1988).
Freyd, G., Kim, S. K. & Horvitz, H. R. Nature 344, 876–879 (1990).
Blair, K. A. Bioessays 17, 299–309 (1995).
Lundgren, F. E., Callahan, C. A., Thor, S. & Thomas, J. D. Development 121, 1769–1773 (1995).
Li, H. et al. EMBO J. 13, 2876–2885 (1994).
Shawlot, W. & Behringer, R. R. Nature 374, 425–430 (1995).
Sheng, H. et al. Science 272, 1004–1007 (1996).
Alpert, S., Hanahan, D. & Teitelman, G. Cell 53, 295–308 (1988).
Herrera, P. L. et al. Development 113, 1257–1265 (1991).
Teitelman, G., Alpert, S., Polack, J. M., Martinez, A. & Hanahan, D. Development 118, 1031–1039 (1993).
Upchurch, B. H., Aponte, G. W. & Liter, A. B. Development 120, 245–252 (1994).
Pictet, R. & Rutter, W. J. in Handbook of Physiology Vol. 1, 25–66 (American Physiological Society, Washington DC, 1972).
Ahlgren, U., Jonsson, J. & Edlund, H. Development 122, 1409–1416 (1996).
Golosow, N. & Grobstein, C. Dev. Biol. 4, 242–255 (1962).
Jonsson, J., Carlsson, L., Edlund, T. & Edlund, H. Nature 371, 606–609 (1994).
Offield, M. F. et al. Development 122, 983–995 (1996).
Lee, J. E. et al. Science 268, 836–844 (1995).
Naya, F. J., Stellrecht, C. M. M. & Tsai, M.-J. Genes Dev. 9, 1009–1019 (1995).
Kuang, J., Zhao, J., Wright, D. A., Saunders, G. F. & Rao, P. N. Proc. Natl Acad. Sci. USA 86, 4982–4986 (1994).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ahlgren, U., Pfaff, S., Jessell, T. et al. Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells. Nature 385, 257–260 (1997). https://doi.org/10.1038/385257a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/385257a0
This article is cited by
-
ISL1 controls pancreatic alpha cell fate and beta cell maturation
Cell & Bioscience (2023)
-
The splanchnic mesenchyme is the tissue of origin for pancreatic fibroblasts during homeostasis and tumorigenesis
Nature Communications (2023)
-
NEUROD1 reinforces endocrine cell fate acquisition in pancreatic development
Nature Communications (2023)
-
Loss of Grem1-lineage chondrogenic progenitor cells causes osteoarthritis
Nature Communications (2023)
-
Clinical Routine Application of the Second-generation Neuroendocrine Markers ISL1, INSM1, and Secretagogin in Neuroendocrine Neoplasia: Staining Outcomes and Potential Clues for Determining Tumor Origin
Endocrine Pathology (2020)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.