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Organogenesis

Pancreatic organogenesis — developmental mechanisms and implications for therapy

Nature Reviews Genetics volume 3, pages 524–532 (2002)Cite this article

Key Points

  • The pancreas is a complex organ that consists of two parts: exocrine, which secretes digestive enzymes into the gut; and endocrine, which secretes the four hormones insulin, glucagon, somatostatin and pancreatic polypeptide.

  • Early studies showed that initial stages of pancreatic development depend on epithelio-mesenchymal interactions, and members of the fibroblast growth factor and epidermal growth factor families of signalling factors were subsequently shown to be part of the signal from the mesenchyme.

  • Mesenchyme has a permissive rather than an instructive role in pancreatic induction.

  • Due to its proximity to the dorsal endoderm, the notochord has been the prime candidate for directing pancreatic development. Although initial in vitro experiments confirmed this prediction, according to more recent studies, the notochord's role is only permissive.

  • Pancreatic growth and differentiation is also affected by Notch signalling — it controls the choice between differentiated endocrine and progenitor cells.

  • Because of neuronal-marker expression, pancreatic endocrine cells were originally proposed to be of neuronal origin. It has now been unequivocally established that they arise from the endoderm.

  • An important note of caution emerges from these studies — a great deal of care is required when cell populations are characterized on the basis of expression markers. Efforts to identify pancreatic stem cells with the aim to treat diabetic patients using cell-replacement therapy might be hampered by the erroneous choice of markers to define pancreatic stem-cell populations.

Abstract

The pancreas is a mixed exocrine and endocrine gland that controls many homeostatic functions. The exocrine pancreas produces and secretes digestive enzymes, whereas the endocrine compartment consists of four distinct hormone-producing cell types. Studies that further our knowledge of the basic mechanisms that underlie the formation of the pancreas will be crucial for understanding the development and homeostasis of this organ and of the mechanisms that cause diabetes. This information is also pivotal for any attempt to generate functional insulin-producing β-cells that are suitable for transplantation.

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Figure 1: The pancreas develops as evaginations of the primitive gut epithelium.
Figure 2: The pancreas is a mixed exocrine and endocrine organ.
Figure 3: Factors that stimulate proliferation of pancreatic cells.
Figure 4: Early stages of pancreatic organogenesis.
Figure 5: Nestin is expressed in pancreatic mesenchymal cells.

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Acknowledgements

Work in my laboratories is supported by the Juvenile Diabetes Research Foundation, New York, the Swedish Research Council, the European Commission, The Göran Gustafsson's Foundation, the Wallenberg Foundation and The Diabetes Research Foundation, Miami. I wish to thank T. Edlund, for critical reading and helpful comments, U. Ahlgren for help with figures, and members of the laboratories at Umeå University, Umeå, Sweden, and the Diabetes Research Institute, University of Miami, USA, for discussions.

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Authors and Affiliations

  1. Umeå Centre for Molecular Medicine, Umeå University, SE-901, 87, Umeå, Sweden

    Helena Edlund

  2. Diabetes Research Institute, University of Miami School of Medicine, 1450 NW 10th Avenue, Miami, 33136, Florida, USA

    Helena Edlund

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DATABASES

Flybase

wingless

LocusLink

BMP

Dll1

EGF

Egfr

FGF

Fgf1

Fgf2

Fgf4

Fgf5

Fgf7

Fgf10

Fgfr1

Fgfr2b

FGFR2

GCK

glucagon

Hes1

HGF

Hlxb9

HNF1A

HNF4A

insulin

IPF1

Isl1

metallothionein

nestin

NeuroD

NEUROD

ngn3

Nkx2.2

Nkx6.1

Notch3

pancreatic polypeptide

Pax6

Pdx1

somatostatin

TGF-β

VEGF

OMIM

Alzheimer disease

MODY

MODY1

MODY2

MODY3

MODY4

MODY5

MODY6

Parkinson disease

type 1 diabetes

type 2 diabetes

Glossary

ACINAR CELLS

A group of secretory cells surrounding a cavity; in the pancreas, they secrete pancreatic enzymes such as α-amylase or chymotrypsinogen.

ZYMOGEN

An inactive enzyme precursor that is chemically altered by hydrolysis to the active form of the enzyme.

ANLAGEN

A precursor tissue before its determination and differentiation.

CATECHOLAMINE

The neurotransmitters dopamine, norepinephrine and epinephrine.

EMBRYOID BODIES

Clumps or cellular structures that arise when embryonic cells are cultured in vitro; they contain tissues from all three germ layers: endoderm, mesoderm and ectoderm.

CELL-TRAPPING EXPERIMENTS

A technique for the selective isolation of cells on the basis of expression of selectable markers that are expressed from a promoter that is specific to the given cell type.

DUODENUM

The first part of the small intestine, immediately posterior to the stomach.

GASTRIC PYLORIC ANTRUM

The most posterior part of the stomach, immediately anterior to the small intestine.

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Edlund, H. Pancreatic organogenesis — developmental mechanisms and implications for therapy. Nat Rev Genet 3, 524–532 (2002). https://doi.org/10.1038/nrg841

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