Developmental Molecular Biology of the Pancreas

  • L. Charles Murtaugh
  • Ondine Cleaver
  • Raymond J. MacDonald
Reference work entry

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.

Keywords

Pancreatic development Acinar development Ductal development Cell delamination Epithelial plexus Pancreatic fate Multipotent progenitors Epithelial to mesenchymal transition 

Notes

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to Jose Cabrera for illustrations, and to Alethia Villasenor, Diana Chong, Ling Shi, and Mike Hale for contributing unpublished data and images.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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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • L. Charles Murtaugh
    • 1
  • Ondine Cleaver
    • 2
  • Raymond J. MacDonald
    • 2
  1. 1.Department of Human GeneticsUniversity of UtahSalt Lake CityUSA
  2. 2.Department of Molecular BiologyThe University of Texas Southwestern Medical CenterDallasUSA

Section editors and affiliations

  • Raul A. Urrutia
    • 1
  • Markus W. Büchler
    • 2
  • John Neoptolemos
    • 3
  1. 1.Mayo Clinic Cancer CenterMayo ClinicRochesterUSA
  2. 2.Department of General, Visceral and Transplantation SurgeryUniversity of HeidelbergHeidelbergGermany
  3. 3.Division of Surgery and OncologyUniversity of LiverpoolLiverpoolUK

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