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Pancreatic Cancer pp 71–117Cite 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 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.

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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processes and developmental anatomy; to Alethia Villasenor, Diana Chong, Ling Shi and Mike Hale for contributing unpublished data and images.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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  1. Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, TX, USA

    Ondine Cleaver & Raymond J. MacDonald

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Cleaver, O., MacDonald, R.J. (2010). Developmental Molecular Biology of the Pancreas. In: Pancreatic Cancer. Springer, New York, NY. https://doi.org/10.1007/978-0-387-77498-5_4

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