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Developmental Molecular Biology of the Pancreas

  • Ondine Cleaver
  • Raymond J. MacDonald

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 associated mesenchyme that direct 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. A number of intrinsic factors, such as transcriptional regulators, and extrinsic signaling factors, such as secreted growth factors, morphogens and cell-surface ligands, have been shown to be determinants of cell-fate decisions, proliferation, or differentiation. The interplay between organ-restricted intrinsic factors and widely used extrinsic factors guides the step-wise 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

Acinar Cell Endocrine Cell Definitive Endoderm Secondary Transition Pancreatic Development 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We thank Chris Wright for the Pdx1-lacZ mice used for Fig. 4-1 . We are indebted to Galvin Swift for critical readings of the manuscript, helpful discussions and invaluable comments; to Jose Cabrera for the tireless creation of beautiful schematics illustrating complex pancreatic processes and developmental anatomy; to Alethia Villasenor, Diana Chong, Ling Shi and Mike Hale for contributing unpublished data and images. This work was supported by NIH R01 grant DK79862-01, JDRF Award 99-2007-472 and a Basil O’Connor March of Dimes Award to O.C., and NIH DK61220 and an American Pancreatic Foundation award to R.J.M.

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Ondine Cleaver
    • 1
  • Raymond J. MacDonald
    • 1
  1. 1.Department of Molecular BiologyThe University of Texas Southwestern Medical CenterDallasUSA

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