Gastrointestinal Tract - Pancreas Development

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Introduction

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.

A study of infants and newborns[1] has shown a poor secretory response, to secretin, that is either absent or minimal at birth and is then acquired during the postnatal period.

Links: Endocrine Pancreas | Exocrine Pancreas


GIT Links: Introduction | Medicine Lecture | Science Lecture | Endoderm | Mouth | Oesophagus | Stomach | Liver | Gall Bladder | Pancreas | Intestine | Tongue | Taste | Enteric Nervous System | Stage 13 | Stage 22 | Abnormalities | Movies | Postnatal | Milk | Tooth | Tongue | Salivary Gland | BGD Lecture | BGD Practical | GIT Terms | Category:Gastrointestinal Tract
GIT Histology Links: Upper GIT | Salivary Gland | Smooth Muscle Histology | Liver | Gall Bladder | 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 | 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 | 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[2] "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[3] "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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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
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References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: Pancreas Embryology

Mustafa Sandıkcı, Levent Karagenc, Mustafa Yıldız Changes on the Pancreas in Experimental Diabetes and the Effect of Lycopene on These Changes: Pdx-1, Ngn-3 and Nestin Expressions. Anat Rec (Hoboken): 2017; PubMed 28921917

Veronica White, Alicia Jawerbaum, Maria Belen Mazzucco, Martin Gauster, Gernot Desoye, Ursula Hiden IGF2 stimulates fetal growth in a sex and organ dependent manner. Pediatr. Res.: 2017; PubMed 28910276

Takeru Matsuda, Yasuo Sumi, Kimihiro Yamashita, Hiroshi Hasegawa, Masashi Yamamoto, Yoshiko Matsuda, Shingo Kanaji, Taro Oshikiri, Tetsu Nakamura, Satoshi Suzuki, Yoshihiro Kakeji Anatomy of the Transverse Mesocolon Based on Embryology for Laparoscopic Complete Mesocolic Excision of Right-Sided Colon Cancer. Ann. Surg. Oncol.: 2017; PubMed 28871557

Hadi Yousefi, Alireza Alihemmati, Pouran Karimi, Mohammad Reza Alipour, Parisa Habibi, Nasser Ahmadiasl Effect of genistein on expression of pancreatic SIRT1, inflammatory cytokines and histological changes in ovariectomized diabetic rat. Iran J Basic Med Sci: 2017, 20(4);423-429 PubMed 28804612

A Garcia-Granero, L Sánchez-Guillén, O Carreño, J Sancho Muriel, E Alvarez Sarrado, D Fletcher Sanfeliu, B Flor Lorente, M Frasson, F Martinez Soriano, E Garcia-Granero Importance of the Moskowitz artery in the laparoscopic medial approach to splenic flexure mobilization: a cadaveric study. Tech Coloproctol: 2017; PubMed 28752340

Development Overview

Human Pancreas Growth (third trimester weight in grams)[4]
  • 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

Embryonic

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.[5] [6][7]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.[8] "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."

Secretagogues

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[9]
  • 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[10] 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[10]

Duct Development

Mouse-pancreas duct formation.jpg

Abnormalities

Listed below are a number of pancreatic developmental abnormalities, see also the 2003 article "Lifetime consequences of abnormal fetal pancreatic development"[11].

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

References

  1. E Lebenthal, P C Lee Development of functional responses in human exocrine pancreas. Pediatrics: 1980, 66(4);556-60 PubMed 6159567
  2. Terumi Kamisawa, Atsutake Okamoto Pancreatographic investigation of pancreatic duct system and pancreaticobiliary malformation. J. Anat.: 2008, 212(2);125-34 PubMed 18194203
  3. Philip A Seymour, Kristine K Freude, Man N Tran, Erin E Mayes, Jan Jensen, Ralf Kist, Gerd Scherer, Maike Sander SOX9 is required for maintenance of the pancreatic progenitor cell pool. Proc. Natl. Acad. Sci. U.S.A.: 2007, 104(6);1865-70 PubMed 17267606
  4. John G Archie, Julianne S Collins, Robert Roger Lebel Quantitative standards for fetal and neonatal autopsy. Am. J. Clin. Pathol.: 2006, 126(2);256-65 PubMed 16891202
  5. A STAUB, L SINN, O K BEHRENS Purification and crystallization of hyperglycemic glycogenolytic factor (HGF). Science: 1953, 117(3049);628-9 PubMed 13056638
  6. A STAUB, L SINN, O K BEHRENS Purification and crystallization of glucagon. J. Biol. Chem.: 1955, 214(2);619-32 PubMed 14381399
  7. W W BROMER, L G SINN, A STAUB, O K BEHRENS The amino acid sequence of glucagon. Diabetes: 1957, 6(3);234-8 PubMed 13427628
  8. Lijie Liu, Jing Guo, Li Yuan, Mei Cheng, Lihua Cao, Hui Shi, Hui Tong, Ning Wang, Wei De Alpha-fetoprotein is dynamically expressed in rat pancreas during development. Dev. Growth Differ.: 2007, 49(8);669-81 PubMed 17880577
  9. Anne-Christine Hick, Jonathan M van Eyll, Sabine Cordi, Céline Forez, Lara Passante, Hiroshi Kohara, Takashi Nagasawa, Pierre Vanderhaeghen, Pierre J Courtoy, Guy G Rousseau, Frédéric P Lemaigre, Christophe E Pierreux Mechanism of primitive duct formation in the pancreas and submandibular glands: a role for SDF-1. BMC Dev. Biol.: 2009, 9;66 PubMed 20003423 | BMC Dev Biol.
  10. 10.0 10.1 Cecil M Benitez, Kun Qu, Takuya Sugiyama, Philip T Pauerstein, Yinghua Liu, Jennifer Tsai, Xueying Gu, Amar Ghodasara, H Efsun Arda, Jiajing Zhang, Joseph D Dekker, Haley O Tucker, Howard Y Chang, Seung K Kim An integrated cell purification and genomics strategy reveals multiple regulators of pancreas development. PLoS Genet.: 2014, 10(10);e1004645 PubMed 25330008
  11. K Holemans, L Aerts, F A Van Assche Lifetime consequences of abnormal fetal pancreatic development. J. Physiol. (Lond.): 2003, 547(Pt 1);11-20 PubMed 12562919

Journals

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


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Cite this page: Hill, M.A. 2017 Embryology Gastrointestinal Tract - Pancreas Development. Retrieved September 25, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Gastrointestinal_Tract_-_Pancreas_Development

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