Gastrointestinal Tract - Pancreas Development

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The Adult Pancreas

This section of notes gives an overview of how the pancreas develops as an exocrine organ associated with the gastrointestinal tract. There is a second description, similar in overview, in relation to the pancreas as an endocrine organ, see Endocrine - Pancreas Development.

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.

The digestive enzyme alpha amylase is the main exocrine enzyme produced by the pancreas (Amy2), and also by salivary glands (Amy1). Study of prenatal fetal [1] and postnatal[2] production of amylase during the first 2 years has shown that the majority of produced initially is salivary amylase. Infants and newborns also show a poor secretory response, to secretin, that is either absent or minimal at birth and is then acquired during the postnatal period.[3] These results taken together suggest that the exocrine pancreas only becomes gradually "functional" postnatally.

Links: Endocrine Pancreas | Exocrine Pancreas

GIT Links: Introduction | Medicine Lecture | Science Lecture | endoderm | mouth | oesophagus | stomach | liver | gallbladder | Pancreas | intestine | mesentery | tongue | taste | enteric nervous system | Stage 13 | Stage 22 | gastrointestinal abnormalities | Movies | Postnatal | milk | tooth | salivary gland | BGD Lecture | BGD Practical | GIT Terms | Category:Gastrointestinal Tract
GIT Histology Links: Upper GIT | Salivary Gland | Smooth Muscle Histology | Liver | Gallbladder | Pancreas | Colon | Histology Stains | Histology | GIT Development
Historic Embryology - Gastrointestinal Tract  
1878 Alimentary Canal | 1882 The Organs of the Inner Germ-Layer The Alimentary Tube with its Appended Organs | 1902 The Organs of Digestion | 1903 Submaxillary Gland | 1906 Liver | 1907 Development of the Digestive System | 1907 Atlas | 1907 23 Somite Embryo | 1908 Liver and Vascular | 1910 Mucous membrane Oesophagus to Small Intestine | 1910 Large intestine and Vermiform process | 1911-13 Intestine and Peritoneum - Part 1 | Part 2 | Part 3 | Part 5 | Part 6 | 1912 Digestive Tract | 1912 Stomach | 1914 Digestive Tract | 1914 Intestines | 1914 Rectum | 1915 Pharynx | 1915 Intestinal Rotation | 1917 Entodermal Canal | 1918 Anatomy | 1921 Alimentary Tube | 1932 Gall Bladder | 1939 Alimentary Canal Looping | 2008 Liver | 2016 GIT Notes | Historic Disclaimer
Human Embryo: 1908 13-14 Somite Embryo | 1921 Liver Suspensory Ligament | 1926 22 Somite Embryo | 1907 23 Somite Embryo | 1937 25 Somite Embryo | 1914 27 Somite Embryo | 1914 Week 7 Embryo
Animal Development: 1913 Chicken | 1951 Frog

Historic Embryology: 1912 Pancreas Development | 1930 Ventral Pancreas

Some Recent Findings

Pancreatic Duct[4] "The long-type accessory pancreatic duct represents a continuation of the main duct of the dorsal pancreatic bud. The short-type accessory pancreatic duct is probably formed by the proximal main duct of the dorsal pancreatic bud and its long inferior branch."

SOX9[5] "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." (More? OMIM Sox9 | Protein Sox9)

More recent papers  
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Development Overview

Human Pancreas Growth (third trimester weight in grams)[6]
  • Functions- exocrine (amylase, alpha-fetoprotein) and endocrine (pancreatic islets)
  • 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)
  • Week 6 - 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
  • Islet cells- cords of endodermal cells form ducts, which cells bud off to form islets
  • Week 7 to 20 - pancreatic hormones secretion increases, small amount maternal insulin
  • Week 10 - glucagon (alpha) differentiate first, somatostatin (delta), insulin (beta) cells differentiate, insulin secretion begins
  • Week 15 - glucagon detectable in fetal plasma
  • Beta cells - stimulate fetal growth, continue to proliferate through to postnatal in infancy, most abundant
  • Maternal diabetes mellitus - hypertrophy of fetal beta cells


Week 6

Pancreas buds

During week 6 about day 41 (Carnegie stage 17, GA week 8) the stomach rotation brings the smaller ventral pancreatic bud dorsally to fuse with the larger dorsal pancreatic bud.

Pancreatic Bud Rotation (animal models)

  • mouse - day 13 to 14 (E13 - E14)
  • pig - 38 to 52 days days post coitum (d.p.c.)
  • cattle - before 45 d.p.c.

Week 8

Late Embryonic (Carnegie stage 22)

Stage22 pancreas a.jpg

Pancreatic Duct

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).

Pancreatic duct developing.jpgPancreas adult.jpg

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).

Pancreas Histology

Pancreas histology 001.jpg Pancreas histology 002.jpg
(Human, H&E x10) (H&E x40)

Links: Gastrointestinal Tract - Pancreas Histology

Pancreas History

1642 - main pancreatic duct (MPD) discovered by Johann Georg Wirsung (1589 - 1643) a German physician who worked as a prosector in Padua. The duct is also called Wirsung's duct.

1724 - accessory pancreatic duct (APD) dissected and delineated by Giovanni Domenico Santorini (1681 - 1737) an Italian anatomist. The duct is also called Santorini's duct.

1833 - Amylase, the form enzyme also found in exocrine pancreas, isolated from a malt solution by Anselme Payen.

1893 - Islets of Langerhans named in honour of Paul Langerhans (1847-1888) by Gustave-Edouard Laguesse (1861-1927) a french histopathologist.

1922 - discovery of insulin by Frederick Banting and John Macleod, two Canadian researchers, and they subsequently win the 1923 Nobel Prize in Medicine. Banting shared his part of the prize money with a younger coworker Charles Best.

1953 - glucagon, originally called "hyperglycemic glycogenolytic factor", purified by Staub, Sinn and Behrens.[7][8][9] See also book JM. Howard and W, Hess (2002) "History of the Pancreas: Mysteries of a Hidden Organ".

Links: Nobel Lecture, September 15, 1925 | Amazon - History of the Pancreas: Mysteries of a Hidden Organ | PDF Article - Purification and Crystallization of Glucagon |

Pancreas Digestive

  • 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 -ì brings ventral and dorsal buds together, fusion of buds
  • Pancreatic duct - ventral bud duct and distal part of dorsal bud, exocrine function

Functions - exocrine (amylase, alpha-fetoprotein)

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

Pancreatic alpha-fetoprotein has been found to change in expression level (in rats) during developent and has been suggested to influence pancreas development.[10] "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."


Secretagogue is a generic term for any substance that stimulates the secretion of another substance from a tissue or organ. In the exocrine pancreas, these are substances that stimulate the acini release of digestive enzymes. Note that bicarbonate and fluid secretion occurs in the pancreatic ducts and its stimulation may differ from enzyme secretion.

  • secretin
  • cholecystokinin
  • vasoactive intestinal polypeptide (VIP)

Duodenum/Pancreas Rotation

Pancreas rotation cartoon After the stomach the initial portion of the gastrointestinal tract tube is the duodenum which initially lies in the midline within the peritoneal cavity.

This region, along with the attached pancreas, undergoes rotation to become a retroperitoneal structure.

This diagram shows the rotation with spinal cord at the top, vertebral body then dorsal aorta then pertioneal wall and cavity.

Note this is a simplified diagram and the liver would push everything to the left during this rotation.

Mouse Pancreas Development

Mouse pancreas development[11]
  • Pancreas develops from distinct dorsal and ventral primordia.
  • Dorsal pancreas - midline endoderm in posterior foregut is a single layer of epithelial cells that contacts notochord, an axial mesoderm-derived structure
  • Ventral pancreas - Laterally, endoderm fated to form ventral pancreas is adjacent to both splanchnic mesoderm and aortic endothelial cells but is not in direct contact with notochord.
  • The notochord and dorsal prepancreatic endoderms remain in contact until about the 13-somite stage in mice, 8.5 d postcoitum (dpc), when midline fusion of the paired dorsal aortas occurs.
  • The first indication of morphogenesis occurs at 22-25 somites in mice (9.5 dpc)
    • dorsal mesenchyme condenses and underlying endoderm evaginates, forming a recognizable dorsal pancreatic bud
    • the ventral bud appears later at ~30 somites (10.25-10.5 dpc). Stimulated by mesenchymal signals, pancreatic epithelial cells proliferate and branch.
  • The accumulated evidence is consistent with the possibility that a unique cell gives rise to all pancreatic cell lineages. The existence of such a pancreatic "stem" cell remains debatable.

(text modified from Seung K. Kim and Matthias Hebrok Intercellular signals regulating pancreas development and function. Genes & Development 15:111-127 2001)

Mouse Pancreas Cell Lineage

In this study[12] mouse cell types were collected at different ages E11 and E15 pancreatic progenitors, E15 acinar cells, E15 endocrine progenitors (EP), E15, E17, P1, P15, 8–12 week beta cells, P1 and 8–12 week alpha cells, and adult duct cells. The following markers were used in determining the lineages, not both endocrine and exocrine cells derive from a common precursor.

  • Neurog3 - Neurogenin-3 (Ngn3) protein encoded in humans by the NEUROG3 gene. A basic helix-loop-helix (bHLH) transcription factor expressed in pancreas endocrine progenitor cells. This factor family involved in neural precursor cell determination in the neuroectoderm. OMIM 604882
  • CD133 - Prominin-1 a glycoprotein encoded in humans by the PROM1 gene.
  • CD24 - Cluster of differentiation 24 or heat stable antigen CD24 (HSA) a protein encoded in humans by the CD24 gene. CD24 is a cell adhesion molecule.
  • CD49f - Integrin alpha-6 (ITGA6) protein encoded in humans by the ITGA6 gene. Associates with a beta protein to form a laminin-binding heterodimers involved in adhesion.

Mouse pancreas cell lineage.jpg

Identification of pancreas cell lineages[12]

Duct Development

Mouse-pancreas duct formation.jpg


Listed below are a number of pancreatic developmental abnormalities, see also the 2003 article "Lifetime consequences of abnormal fetal pancreatic development"[13]

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.

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

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

Additional Images

Historic Images


  1. Ogita S, Noma H, Kawamura T, Shimura K, Ohnishi M, Ishiko O & Sugawa T. (1978). Differentiation of amylase isozyme in amniotic fluid with fetal age. Am. J. Obstet. Gynecol. , 131, 63-8. PMID: 645785
  2. Tye JG, Karn RC & Merritt AD. (1976). Differential expression of salivary (Amy1) and pancreatic (Amy2) human amylase loci in prenatal and postnatal development. J. Med. Genet. , 13, 96-102. PMID: 933119
  3. Lebenthal E & Lee PC. (1980). Development of functional responses in human exocrine pancreas. Pediatrics , 66, 556-60. PMID: 6159567
  4. Kamisawa T & Okamoto A. (2008). Pancreatographic investigation of pancreatic duct system and pancreaticobiliary malformation. J. Anat. , 212, 125-34. PMID: 18194203 DOI.
  5. Seymour PA, Freude KK, Tran MN, Mayes EE, Jensen J, Kist R, Scherer G & Sander M. (2007). SOX9 is required for maintenance of the pancreatic progenitor cell pool. Proc. Natl. Acad. Sci. U.S.A. , 104, 1865-70. PMID: 17267606 DOI.
  6. Archie JG, Collins JS & Lebel RR. (2006). Quantitative standards for fetal and neonatal autopsy. Am. J. Clin. Pathol. , 126, 256-65. PMID: 16891202 DOI.
  7. STAUB A, SINN L & BEHRENS OK. (1953). Purification and crystallization of hyperglycemic glycogenolytic factor (HGF). Science , 117, 628-9. PMID: 13056638
  8. STAUB A, SINN L & BEHRENS OK. (1955). Purification and crystallization of glucagon. J. Biol. Chem. , 214, 619-32. PMID: 14381399
  9. BROMER WW, SINN LG, STAUB A & BEHRENS OK. (1957). The amino acid sequence of glucagon. Diabetes , 6, 234-8. PMID: 13427628
  10. Liu L, Guo J, Yuan L, Cheng M, Cao L, Shi H, Tong H, Wang N & De W. (2007). Alpha-fetoprotein is dynamically expressed in rat pancreas during development. Dev. Growth Differ. , 49, 669-81. PMID: 17880577 DOI.
  11. Hick AC, van Eyll JM, Cordi S, Forez C, Passante L, Kohara H, Nagasawa T, Vanderhaeghen P, Courtoy PJ, Rousseau GG, Lemaigre FP & Pierreux CE. (2009). Mechanism of primitive duct formation in the pancreas and submandibular glands: a role for SDF-1. BMC Dev. Biol. , 9, 66. PMID: 20003423 DOI.
  12. 12.0 12.1 Benitez CM, Qu K, Sugiyama T, Pauerstein PT, Liu Y, Tsai J, Gu X, Ghodasara A, Arda HE, Zhang J, Dekker JD, Tucker HO, Chang HY & Kim SK. (2014). An integrated cell purification and genomics strategy reveals multiple regulators of pancreas development. PLoS Genet. , 10, e1004645. PMID: 25330008 DOI.
  13. Holemans K, Aerts L & Van Assche FA. (2003). Lifetime consequences of abnormal fetal pancreatic development. J. Physiol. (Lond.) , 547, 11-20. PMID: 12562919 DOI.


Zakowski JJ & Bruns DE. (1985). Biochemistry of human alpha amylase isoenzymes. Crit Rev Clin Lab Sci , 21, 283-322. PMID: 2578342 DOI.


Tye JG, Karn RC & Merritt AD. (1976). Differential expression of salivary (Amy1) and pancreatic (Amy2) human amylase loci in prenatal and postnatal development. J. Med. Genet. , 13, 96-102. PMID: 933119


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

Pathophysiology of the Endocrine System The Endocrine Pancreas

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

Search Bookshelf Pancreas Development

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Search Pubmed Now: Pancreas Development | Exocrine Pancreas Development

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Cite this page: Hill, M.A. (2019, February 16) Embryology Gastrointestinal Tract - Pancreas Development. Retrieved from

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