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Pancreatic Cancer pp 89–145Cite as

Developmental Molecular Biology of the Pancreas

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Abstract

Pancreatic organogenesis is a complex and coordinated process that generates a compound gland of exocrine tissue composed of acini and ducts and endocrine tissue organized in islets of Langerhans. Both tissues originate from the same early endodermal epithelium through cell-cell signaling exchanges with adjacent tissues, including associated mesenchyme that directs a cascade of transcriptional regulatory events. Current research is aimed at elucidating the formation of pancreatic cell types and the molecular mechanisms that shape the anatomy and physiology of the pancreas. Insights into these questions come from a combination of mouse and human genetics and, increasingly, pluripotent stem cell-based models of organogenesis. These studies have identified both intrinsic factors, such as transcriptional regulators, and extrinsic signaling factors, such as secreted growth factors, morphogens, and cell-surface ligands, as determinants of cellular fate decisions, proliferation, or differentiation. The interplay between organ-restricted intrinsic factors and widely used extrinsic factors guides the stepwise process of pancreatic development from early endodermal patterning and specification of the initial pancreatic field to expansion of pools of progenitors, resolution of individual cell types, and the differentiation of mature exocrine and endocrine cells. A better understanding of pancreatic development is proving useful for comprehending the regulatory defects that drive pancreatic carcinogenesis and for devising effective therapies to correct those defects.

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Acknowledgments

We thank Chris Wright for the Pdx1-lacZ mice used for Fig. 1. We are indebted to Galvin Swift helpful discussions and invaluable comments, to Jose Cabrera for illustrations, and to Alethia Villasenor, Diana Chong, Ling Shi, and Mike Hale for contributing unpublished data and images. This work was supported by NIH grant CA194941 to L.C.M., NIH grant DK79862-01 and JDRF Award 99-2007-472 to O.C., and NIH grant DK61220 to R.J.M.

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Authors and Affiliations

  1. Department of Human Genetics, University of Utah, Salt Lake City, UT, 84112, USA

    L. Charles Murtaugh

  2. Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Ondine Cleaver & Raymond J. MacDonald

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  1. L. Charles Murtaugh
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Correspondence to L. Charles Murtaugh .

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Editors and Affiliations

  1. Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany

    John P. Neoptolemos

  2. Division of Research Department of Surgery and Genomic Sciences and Precision Medicine Center (GSPMC), Medical College of Wisconsin, Milwaukee, Wisconsin, USA

    Raul Urrutia

  3. Division of Medical Oncology, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA

    James L. Abbruzzese

  4. Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany

    Markus W. Büchler

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  1. Mayo Clinic Cancer Center, Mayo Clinic, 200 First Street SW, 55905, Rochester, MN, USA

    Raul A. Urrutia

  2. Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany

    Markus W. Büchler

  3. Division of Surgery and Oncology, University of Liverpool, Daulby Street, Liverpool, UK

    John Neoptolemos

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Murtaugh, L.C., Cleaver, O., MacDonald, R.J. (2018). Developmental Molecular Biology of the Pancreas. In: Neoptolemos, J., Urrutia, R., Abbruzzese, J., Büchler, M. (eds) Pancreatic Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-7193-0_4

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