UNSW Embryology

Gastrointestinal Tract - Pancreas

© Dr Mark Hill (2009)

Acknowledgements

Introduction

This section of notes gives an overview of how the pancreas develops. At the foregut/midgut junction the septum transversum generates 2 pancreatic buds (dorsal and ventral endoderm) which will fuse to form the pancreas. The dorsal bud arises first and generates most of the pancreas. The ventral bud arises beside the bile duct and forms only part of the head and uncinate process of the pancreas.

Stage 22 Embryo Pancreas

In the fetal period islet cell clusters (icc) differentiate from pancratic bud endoderm. These cell clusters form acini and ducts (exocrine). On the edge of these cell clusters pancreatic islets (endocrine) also form.

The mature pancreas has both exocrine (GIT enzymes) and endocrine (hormonal) functions. Pancreatic GIT enzyme function is to alkilate the acidic stomach contents in the duodenum to allow further enzymatic digestion of proteins (amylase). During development there is also a secretion of pancreatic alpha-fetoprotein which may also have a role in pancreatic development.

Adult Pancreas

The pancreas exocrine function begins after birth, while the endocrine function (hormone release) can be measured from 10 to 15 weeks onward. At this stage, it is not clear what the exact roles of these hormones are in regulating fetal growth.

Pancreatic hormonal function is to secrete insulin and glucagon which together regulate blood glucose levels and also to secrete somaostatin which regulates intestinal function. (More? Endocrine Notes - Pancreas)

Page Links: Introduction | Some Recent Findings | Components of Pancreas Formation | Pancreatic Buds | Pancreas Digestive | Pancreas Histology | Pancreatic Duct Variations | Abnormalities | References | Glossary

Other Pages: Endocrine Notes- Pancreas | Abnormal Development - Maternal Diabetes

Some Recent Findings

GATA4 / GATA6 Watt AJ, Zhao R, Li J, Duncan SA. Development of the mammalian liver and ventral pancreas is dependent on GATA4. BMC Dev Biol. 2007 Apr 23;7(1):37 (More? OMIM - GATA4)

"GATA4, a zinc finger transcription factor, is strongly expressed in these endodermal domains and molecular analyses have implicated GATA4 in potentiating liver gene expression during the onset of hepatogenesis. ...Analyses of pancreatic development revealed a complete absence of the ventral but not the dorsal pancreas in Gata4-/- embryos. Moreover, Gata6-/- embryos displayed a similar, although less dramatic phenotype, suggesting a critical role for multiple GATA factors at the earliest stages of ventral pancreas development."

SOX9 is involved in pancreas organogenesis as a progenitor cell specific marker and maintenance factor. Seymour PA, Freude KK, Tran MN, Mayes EE, Jensen J, Kist R, Scherer G, Sander M. SOX9 is required for maintenance of the pancreatic progenitor cell pool. Proc Natl Acad Sci U S A. 2007 Jan 31) (More? OMIM Sox9 | Protein Sox9)

"We show that Sox9 maintains pancreatic progenitors by stimulating their proliferation, survival, and persistence in an undifferentiated state. Our finding that SOX9 regulates the Notch-effector HES1 suggests a Notch-dependent mechanism and establishes a possible genetic link between SOX factors and Notch."

Components of Pancreas Formation

primitive endoderm

foregut diverticulum
foregut-midgut junction septum transversum pancreatic primordium left & right lobes body/tail uncinate process pancreas
midgut region hindgut diverticulum (pocket)

Modified from The Anatomical Basis of Mouse Development Kaufman & Bard, 1999 Academic Press

Pancreatic Buds

• Pancreatic buds- endoderm, covered in splanchnic mesoderm
• Pancreatic bud formation – duodenal level endoderm, splanchnic mesoderm forms dorsal and ventral mesentery, dorsal bud (larger, first), ventral bud (smaller, later)
• Duodenum growth/rotation – brings ventral and dorsal buds together, fusion of buds
• Pancreatic duct – ventral bud duct and distal part of dorsal bud, exocrine function

Pancreas Digestive

Postnatally alkali pancreatic juice is secreted into the duodenum and contains a number of enzymes required for the continued digestion of contents emptyied from the stomach into the duodenum. In the adult approximately 1.5 litres of pancreatic juice are secreted each day.

Enzymes: trypsin, chymotrypsin and carboxypeptidase, ribonuclease, deoxyribonuclease, pancreatic amylase, pancreatic lipase.

Pancreatic amylase an enzyme which digests starch to maltose. Postnatally, a blood test to detect amylase can be used to diagnose and monitor acute or chronic pancreatitis (pancreas inflammation). trypsin, chymotrypsin and carboxypeptidase

Pancreatic alpha-fetoprotein has been found to change in expression level (in rats) during developent and has been suggested to influence pancreas development.

Reference: Liu L, Guo J, Yuan L, Cheng M, Cao L, Shi H, Tong H, Wang N, De W. Alpha-fetoprotein is dynamically expressed in rat pancreas during development. Dev Growth Differ. 2007 Oct;49(8):669-81.

"Immunolocalization for AFP revealed that a positive reactivity was detectable at E15.5 pancreas, became stronger in the cytoplasm of mesenchyme cells at E18.5, and declined after birth to a nearly undetectable level in adults."

Pancreatic Duct Variations

The initial formation of the pancreas as two separate lobes each with their own duct that fuses leads a range of anatomical variations in the adult exocrine pancreatic duct. Pancreatic duct five variation classification: common, ansa pancreatica, branch fusion, looped, and separated.Accessory pancreatic duct (APD, of Santorini) in the embryo is the main drainage duct of the dorsal pancreatic bud emptying into the minor duodenal papilla. In the adult it has been further classified as either long-type (joins main pancreatic duct at pancreas neck portion) and short-type (joins main pancreatic duct near first inferior branch).

Main Pancreatic Duct (MPD or Wirsung's duct) forms within the dorsal pancreatic bud and is present in the body and tail of the pancreas. Discovered by Johann Georg Wirsung (1589 - 1643) a German physician who worked as a prosector in Padua.

Accessory Pancreatic Duct (APD or Santorini’s duct) is present mainly in the head of the pancreas. Originally dissected and delineated by Giovanni Domenico Santorini (1681 - 1737) an Italian anatomist.

 

Endoscopic Retrograde Cholangiopancreatography (ERCP) is a medical procedure which allows an injected dye to display the duct system on an x ray (pancreatograms).

Reference: Kamisawa T, Okamoto A. Pancreatographic investigation of pancreatic duct system and pancreaticobiliary malformation. J Anat. 2008 Feb;212(2):125-34.

The pancreatic duct(s) exist as a number of anatomical variations due to the embryological origin from the dorsal and ventral panceas buds formation and later fusion.

Two Main Accessory Pancreatic Duct Variations/Forms long-type - forms a straight line and joins the main pancreatic duct at the neck portion of the pancreas. short-type - joins the main pancreatic duct near its first inferior branch (More? Kamisawa T, Okamoto A., 2008)
	Accessory Pancreatic Duct Anatomical Variations (MAP; major duodenal papilla, MIP; minor duodenal papilla) (Image: Kamisawa, T., etal., Digestive Endoscopy, 10: 308-311, 1998)

 

Adult Pancreas duct emptying into the Duodenum

 

 

Pancreas Histology

(Human, H&E)	Secretory Acini
(More? Pancreas Endocrine Histology)	(Images: Lutz Slomianka, UWA Blue Histology)

Abnormalities

Accessory Pancreatic Tissue pancreatic tissue located in associated gastrointestinal tract tissues/organs such as the wall of the stomach, duodenum, jejunum or Meckel's diverticulum.

Annular Pancreas - (1 in 7,000 people) pancreas forms as a "ring" of tissue surrounding the duodenum which is subsequently narrowed.

Diabetes Mellitus Maternal diabetes (and hyperglycaemia) have been shown to lead to increased fetal islet hyperplasia of the insulin producing beta cells and insulin secretion. (More? Diabetes Mellitus | Maternal Diabetes | Endocrine Notes- Pancreas)

Intrauterine growth restriction can lead to a delayed development of the insulin producing beta cells and low insulin secretion.

Tumours Serous Cystadenoma (endocrine tumour), Somatostatinoma (tumour of delta cell origin), intraductal papillary-mucinous neoplasm

References:Holemans K, Aerts L, Van Assche FA.Lifetime consequences of abnormal fetal pancreatic development. J Physiol. 2003 Feb 15;547(Pt 1):11-20.

Links: NIH Genes and Disease Chapter 41 - Endocrine | Medline Plus - Annular Pancreas |

References

Links: Journals | Online Textbooks | Search Textbooks | PubMed | | Search PubMed | Glossary

See also book JM. Howard and W, Hess (2002) "History of the Pancreas: Mysteries of a Hidden Organ" (Amazon Link).

Journals

Pancreas

Pancreas The official journal of the American Pancreatic Association and the Japan Pancreas Society

Pancreatology Official Journal of the International Association of Pancreatology (IAP); European Pancreatic Club (EPC)and 16 other societies and study groups.

Journal of the Pancreas electronic journal of pancreatology

Online Textbooks

Endocrinology: An Integrated Approach Nussey, S.S. and Whitehead, S.A. Oxford, UK: BIOS Scientific Publishers, Ltd; 2001. table of Contents

NIH Genes & Disease Chapter 41 - Endocrine

Developmental Biology (6th ed) Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000.

Molecular Biology of the Cell (4th Edn) Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter. New York: Garland Publishing; 2002. table 15-1. Some Hormone-induced Cell Responses Mediated by Cyclic AMP

Health Services/Technology Assessment Text (HSTAT) Bethesda (MD): National Library of Medicine (US), 2003 Oct.

Search NLM Online Textbooks- "pancreas development" : Endocrinology | Molecular Biology of the Cell | The Cell- A molecular Approach

Earlier reference search results Pancreas Development (1999)

PubMed

Reviews

• Gasa R. Transcriptional control of pancreatic endocrine cell development. Drug News Perspect. 2005 Nov;18(9):567-76. Review.
• Lucas MJ. Diabetes complicating pregnancy. Obstet Gynecol Clin North Am. 2001 Sep;28(3):513-36. Review.
• Grapin-Botton A. Ductal cells of the pancreas. Int J Biochem Cell Biol. 2005 Mar;37(3):504-10. Review.

Articles

• Kamisawa T, Okamoto A. Pancreatographic investigation of pancreatic duct system and pancreaticobiliary malformation. J Anat. 2008 Feb;212(2):125-34.
• Liu L, Guo J, Yuan L, Cheng M, Cao L, Shi H, Tong H, Wang N, De W. Alpha-fetoprotein is dynamically expressed in rat pancreas during development. Dev Growth Differ. 2007 Oct;49(8):669-81.
• Collombat P, Hecksher-Sorensen J, Serup P, Mansouri A. Specifying pancreatic endocrine cell fates. Mech Dev. 2006 Jul;123(7):501-12. "... apparently identical pool of cells originating from the early gut endoderm, which are successively specified towards the pancreatic, endocrine, and hormone-expressing cell lineages. Numerous studies have outlined the crucial roles exerted by transcription factors in promoting the cell destiny, defining the cell identity and maintaining a particular cell fate. This review focuses on the mechanisms regulating the morphogenesis of the pancreas with particular emphasis on recent findings concerning the transcription factor hierarchy orchestrating endocrine cell fate allocation."
• Duvillie B, Attali M, Bounacer A, Ravassard P, Basmaciogullari A, Scharfmann R. The mesenchyme controls the timing of pancreatic beta-cell differentiation. Diabetes. 2006 Mar;55(3):582-9. "...mesenchyme controls the timing of beta-cell differentiation both upstream and downstream of transcription factor neurogenin 3 (Ngn3)."
• Sheffield JS, Butler-Koster EL, Casey BM, McIntire DD, Leveno KJ. Maternal diabetes mellitus and infant malformations. Obstet Gynecol. 2002 Nov;100(5 Pt 1):925-30.
• Schaefer-Graf UM, Buchanan TA, Xiang A, Songster G, Montoro M, Kjos SL. Patterns of congenital anomalies and relationship to initial maternal fasting glucose levels in pregnancies complicated by type 2 and gestational diabetes. Am J Obstet Gynecol. 2000 Feb;182(2):313-20.
• Schaefer UM, Songster G, Xiang A, Berkowitz K, Buchanan TA, Kjos SL. Congenital malformations in offspring of women with hyperglycemia first detected during pregnancy. Am J Obstet Gynecol. 1997 Nov;177(5):1165-71.

Search PubMed

Search Feb2008 "pancreas development" 9,492 reference articles of which 1,467 were reviews.

Search PubMed: term= pancreas+development

Earlier reference search results Pancreas Development (1999)

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