Gastrointestinal Tract - Liver Development
|Embryology - 13 Oct 2015 Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Movies
- 4 Liver Development Stages
- 5 Liver Buds
- 6 Liver Structural Origins
- 7 Components of Liver Formation
- 8 Development
- 9 Ductal Plate
- 10 Bile Secretion
- 11 Liver Blood Flow
- 12 Hepatocytes
- 13 Kupffer Cells
- 14 Liver Associated Vessels
- 15 Adult Liver Transplants
- 16 Histology
- 17 Abnormalities
- 18 References
- 19 Additional Images
- 20 Glossary Links
This section of notes gives an overview of how the liver develops. The transverse septum (septum transversum) arises at an embryonic junctional site. The junctional region externally is where the ectoderm of the amnion meets the endoderm of the yolk sac. The junctional region internally is where the foregut meets the midgut. The mesenchymal structure of the transverse septum provides a support within which both blood vessels and the liver begin to form. Arises at embryonic junction (septum transversum): externally is where ectoderm of amnion meets endoderm of yolk sac and internally is where the foregut meets the midgut. Mesenchymal structure of transverse septum provides a support within which both blood vessels and liver begin to form in the underlying splanchnic mesoderm.
In the early embryo, the liver and heart grow rapidly forming obvious external swellings on the ventral embryo surface. The liver's initial embryonic function is mainly cardiovascular. Firstly, as a vascular connection between the developing placental vessels to the heart. Secondly, as a haemopoietic tissue where blood stem cells reside before bone marrow development.
See also Liver Histology showing both developmental and adult histology.
- GIT Links: Introduction | Medicine Lecture | Science Lecture | Endoderm | Stomach | Liver | Gall Bladder | Pancreas | Intestine | Tongue | Taste | Enteric Nervous System | Stage 13 | Stage 22 | Abnormalities | Movies | Postnatal | Milk | Tooth | Tongue | BGD Lecture | BGD Practical | Category:Gastrointestinal Tract
Some Recent Findings
|More recent papers|
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.
J Kargl, L Andersen, C Hasenöhrl, D Feuersinger, A Stančić, A Fauland, C Magnes, A El-Heliebi, S Lax, S Uranitsch, J Haybaeck, A Heinemann, R Schicho GPR55 promotes migration and adhesion of colon cancer cells indicating a role in metastasis. Br. J. Pharmacol.: 2015; PubMed 26436760
Eleni A Karavia, Aikaterini Hatziri, Christina Kalogeropoulou, Nikolaos I Papachristou, Eva Xepapadaki, Caterina Constantinou, Anastasios Natsos, Peristera-Ioanna Petropoulou, Shlomo Sasson, Dionysios J Papachristou, Kyriakos E Kypreos Deficiency in Apolipoprotein A-I ablates the pharmacological effects of metformin on plasma glucose homeostasis and hepatic lipid deposition. Eur. J. Pharmacol.: 2015; PubMed 26420354
Hee Chul Yu, Ji Hyun Kim, Gen Murakami, José Francisco Rodríguez-Vázquez, Baik Hwan Cho An anomalous portal vein crossing the lesser sac and ending at the upper part of ductus venosus. Anat Cell Biol: 2015, 48(3);218-21 PubMed 26417483
Adrian Bartos, Dana Monica Bartos, Caius Breazu, Miana Hosu, Raluca Stoian, Cornel Iancu Cytoreductive surgery (CR) followed by hyperthermic intraperitoneal chemotherapy (HIPEC): a chance of survival for patients with advanced colorectal cancer. J Gastrointestin Liver Dis: 2015, 24(3);392-3 PubMed 26405715
Yan Shi, Li Guo, Lu Shi, Jinyang Yu, Min Song, Yana Li Caffeic Acid Phenethyl Ester inhibit Hepatic Fibrosis by Nitric Oxide Synthase and Cystathionine Gamma-Lyase in Rats. Med. Sci. Monit.: 2015, 21;2774-2780 PubMed 26378818
Liver Development Stages
||hepatic diverticulum development|
|| cell differentiation
septum transversum forming liver stroma
hepatic diverticulum forming hepatic trabeculae
||epithelial cord proliferation enmeshing stromal capillaries|
|| hepatic gland and its vascular channels enlarge
hematopoietic function appeared
|| obturation due to epithelial proliferation
bile ducts became reorganized (continuity between liver cells and gut)
|| biliary ductules developed in periportal connective tissue
produces ductal plates that receive biliary capillaries
|Human data from Godlewski G, etal, see also liver development in the rat during the embryonic period (Carnegie stages 15-23). (More? Timeline human development)|
|Embryonic Liver Development Timeline|
|This information is from a recent study of the human embryonic liver from week 5 to 8 (GA 7 to 9; Carnegie stage 14 to 23).|
|Carnegie Stage||Age||CRL (mm)||Biliary system||Vascular||Hepatic parenchyma|
|21||53||22.5||Bile duct morphology as earlier stage. Common bile duct empties at the level of the proximal duodenum.||
||Hepatic parenchyma looks like a large rounded mass.|
|23||58||27||Bile duct morphology as earlier stage.||
|Links: Liver Development | Carnegie stage 14 | Carnegie stage 18 | Carnegie stage 21 | Carnegie stage 23 | Timeline human development|
- Differentiates to form the hepatic diverticulum and hepatic primordium, generates the gall bladder then divides into right and left hepatic (liver) buds.
- Three connecting stalks (cystic duct, hepatic ducts) which fuse to form bile duct.
Left Hepatic Bud
- left lobe, quadrate, caudate (both q and c anatomically Left)
- caudate lobe of human liver consists of 3 anatomical parts: Spiegel's lobe, caudate process, and paracaval portion.
Right Hepatic Bud
- right lobe
Liver Structural Origins
- Hepatic Buds - form hepatocytes, produce bile from week 13 (forms meconium of newborn)
- Vitelline Veins - form sinusoids
- Mesenchyme - form connective tissue and Kupffer cells
Function - Haemopoiesis
Embryonic liver also involved in blood formation, after the yolk sac and blood islands acting as a primary site.
Components of Liver Formation
Data from mouse 
Hepatoblasts - endoderm-derived cells can differentiate into either:
- hepatocytes - populate the bulk of the liver parenchyma.
- cholangiocytes - line the intrahepatic bile ducts.
The images below link to larger cross-sections of the mid-embryonic period (end week 4) stage 13 embryo starting just above the level of the liver and then in sequence through the liver to the level of the stomach. Note the relative position of the liver with respect to the abdominal cavity, the gall bladder and the heart.
The transverse septum differentiates to form the hepatic diverticulum and the hepatic primordium, these two structures together will go on to form different components of the mature liver and gall bladder. At this stage large vascular channels can be seen coursing through the liver primordium.
- Links: Carnegie stage 13 - serial sections | Embryo Serial Sections | Embryo Carnegie stage 13 Movies
|Virtual Slide Features - Stage 22 Liver|
|Virtual Slide - Stage 22 Liver and Ductus Venosus All Virtual Slides
The links shown in the table below are to specific features shown on the Human embryo (stage 22) Liver and Ductus Venosus virtual slide.
Clicking the text will open the slide at a detailed view with the structure generally located in the centre of the view. The slide then can also be zoomed out from the set magnification using the controls in the upper left or the mouse.
Use your browser back button to return to this table.
|You can also make your own selected feature view.
See also Permalink help
The images below link to larger cross-sections of the end of the embryonic period (week 8) stage 22 embryo starting just above the level of the liver and then in sequence through the entire liver. (Note the sections are viewed from below, LR axis is reversed)
The rapidly developing liver also forms a visible surface bulge on the embryo directly under the heart bulge. The liver now occupies the entire ventral body cavity with parts of the gastrointestinal tract and urinary system "embedded" within its structure. Note in this image the large central ductus venosus.
- Links: Carnegie stage 22 - serial sections | Embryo Serial Sections | Embryo Carnegie stage 22 Movies
Selected Stage 22 Images
|E3 Overview of liver region for selected high power views shown below. Note the position and size of the developing liver spanning the entire abdomen and within the liver the large central ductus venosus.|
|E4 Central veins of liver. Radiating appearance of hepatic sinusoids. unlabeled version|
|E5 Central vein with endothelial lining, containing nucleated erythrocytes, fetal red blood cells. The fetal liver has an important haemopoietic role. unlabeled version|
The ductal plate is a primitive biliary epithelium which develops in mesenchyme adjacent to portal vein branches (periportal hepatoblasts). During liver development it is extensively reorganised (ductal plate remodelling) within the developing liver to form the intrahepatic bile ducts (IHBD). If remodelling does not occur, leading to excess of embryonic bile duct structures in the portal tract, these developmental abnormalities are described as "ductal plate malformation" (DPM).
Ductal Plate Malformations
- Interlobular bile ducts - autosomal recessive polycystic kidney disease
- Smaller interlobular ducts - von Meyenburg complexes
- Larger intrahepatic bile ducts - Caroli's disease
The epithelial cells that line the bile ducts are called cholangiocytes.
The pathway below describes the production and passage of bile for final excretion into the duodenum:
- hepatocytes produce bile
- secreted into bile canaliculi
- connected to intrahepatic bile ducts
- intrahepatic bile ducts connect to the hepatic duct
- then the cystic duct for storage in the gallbladder
- then the common bile duct into the duodenum
The term extrahepatic bile ducts (EHBDs) is used to describe the hepatic, cystic, and common bile ducts.
The developing bile ducts express VEGF while hepatoblasts express angiopoietin-1, these two signals are thought to regulate arterial vasculogenesis and remodeling of the hepatic artery respectively.
Liver Blood Flow
Dual blood supply of the liver merges upon entry into the liver lobule at the portal field.
- branches of the portal vein
- branches of the hepatic artery
The blood flows along the sinusoid and exits at the central vein.
These are the adult functional cells forming the majority of the liver (80% of the cells).
Many different functions including:
- Storage of substances including glucose (as glycogen), vitamin A (possibly in specialized adipocytes), vitamin B12, folic acid and iron.
- Lipid Turnover synthesis of plasmalipoproteins
- Plasma Protein Synthesis albumin, alpha and beta globulins, prothrombin, fibrinogen
- Metabolism fat soluble compounds (drugs, insecticides), steroid hormones turnover
- Secretion bile (about 1 litre/day)
Kupffer Cells are a population of tissue macrophages found in the lumen of hepatic sinusoids, their role is endocytic against blood-borne materials entering the liver.
Primordial (primitive) macrophages arise in the yolk sac and then differentiate into fetal macrophages, either of these enter the blood and migrate into the developing liver.
Kupffer Cells image
- Search PubMed: Kupffer cell development
Liver Associated Vessels
Adult Liver Transplants
- About 6,000 liver transplant operations are performed in the United States (http://www.liverfoundation.org/education/info/transplant/)
- About 600–700 in the UK every year (http://www.britishlivertrust.org.uk/home/the-liver/liver-transplantation/a-history-of-liver-transplantation-and-current-statistics.aspx).
- The main limitation on numbers are the availability of donor organs.
The Liver Lobule
Adult liver Portal Triad
- Links: Liver Histology
Congenital absence of the portal vein (CAPV) - a rare abnormality where the intestinal and splenic venous drainage bypass the liver and drain directly into the systemic veins through various porto-systemic shunts.
- Peter S Vestentoft, Peter Jelnes, Branden M Hopkinson, Ben Vainer, Kjeld Møllgård, Bjørn Quistorff, Hanne C Bisgaard Three-dimensional reconstructions of intrahepatic bile duct tubulogenesis in human liver. BMC Dev. Biol.: 2011, 11;56 PubMed 21943389
- Ewa Wandzioch, Kenneth S Zaret Dynamic signaling network for the specification of embryonic pancreas and liver progenitors. Science: 2009, 324(5935);1707-10 PubMed 19556507 | PMC2771431 | Science
- Ewa Wandzioch, Kenneth S Zaret Dynamic signaling network for the specification of embryonic pancreas and liver progenitors. Science: 2009, 324(5935);1707-10 PubMed 19556507
- 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
- G Godlewski, R Gaubert-Cristol, S Rouy, M Prudhomme Liver development in the rat and in man during the embryonic period (Carnegie stages 11-23). Microsc. Res. Tech.: 1997, 39(4);314-27 PubMed 9407542
- G Godlewski, R Gaubert-Cristol, S Rouy, M Prudhomme Liver development in the rat during the embryonic period (Carnegie stages 15-23). Acta Anat (Basel): 1997, 160(3);172-8 PubMed 9718390
- Martin Lhuaire, Romain Tonnelet, Yohann Renard, Tullio Piardi, Daniele Sommacale, Fabrice Duparc, Marc Braun, Marc Labrousse Developmental anatomy of the liver from computerized three-dimensional reconstructions of four human embryos (from Carnegie stage 14 to 23). Ann. Anat.: 2015, 200;105-113 PubMed 25866917 | Ann Anat.
- Karen Pauwelyn, Philip Roelandt, Tineke Notelaers, Pau Sancho-Bru, Johan Fevery, Catherine M Verfaillie Culture of mouse embryonic stem cells with serum but without exogenous growth factors is sufficient to generate functional hepatocyte-like cells. PLoS ONE: 2011, 6(8);e23096 PubMed 21829697 | PLoS One.
- Kaufman and Bard, The Anatomical Basis of Mouse Development 1999 Academic Press
- Galit Tzur, Ariel Israel, Asaf Levy, Hila Benjamin, Eti Meiri, Yoel Shufaro, Karen Meir, Elina Khvalevsky, Yael Spector, Nathan Rojansky, Zvi Bentwich, Benjamin E Reubinoff, Eithan Galun Comprehensive gene and microRNA expression profiling reveals a role for microRNAs in human liver development. PLoS ONE: 2009, 4(10);e7511 PubMed 19841744 | PMC2760133 | PLoS
- James M Crawford Development of the intrahepatic biliary tree. Semin. Liver Dis.: 2002, 22(3);213-26 PubMed 12360416
- Makoto Naito, Go Hasegawa, Yusuke Ebe, Takashi Yamamoto Differentiation and function of Kupffer cells. Med Electron Microsc: 2004, 37(1);16-28 PubMed 15057601
- Ruchi Sharma, Sebastian Greenhough, Claire N Medine, David C Hay Three-dimensional culture of human embryonic stem cell derived hepatic endoderm and its role in bioartificial liver construction. J. Biomed. Biotechnol.: 2010, 2010;236147 PubMed 20169088 | PMC2821762
Takahiro Nakamura, Katsuya Sakai, Toshikazu Nakamura, Kunio Matsumoto Hepatocyte growth factor twenty years on: Much more than a growth factor. J. Gastroenterol. Hepatol.: 2011, 26 Suppl 1;188-202 PubMed 21199531
Hisami Ando Embryology of the biliary tract. Dig Surg: 2010, 27(2);87-9 PubMed 20551648
Janet W C Kung, Ian S Currie, Stuart J Forbes, James A Ross Liver development, regeneration, and carcinogenesis. J. Biomed. Biotechnol.: 2010, 2010;984248 PubMed 20169172
Karim Si-Tayeb, Frédéric P Lemaigre, Stephen A Duncan Organogenesis and development of the liver. Dev. Cell: 2010, 18(2);175-89 PubMed 20159590
John Le Lay, Klaus H Kaestner The Fox genes in the liver: from organogenesis to functional integration. Physiol. Rev.: 2010, 90(1);1-22 PubMed 20086072
T Roskams, V Desmet Embryology of extra- and intrahepatic bile ducts, the ductal plate. Anat Rec (Hoboken): 2008, 291(6);628-35 PubMed 18484608
Vincenzo Cardinale, Yunfang Wang, Guido Carpino, Gemma Mendel, Gianfranco Alpini, Eugenio Gaudio, Lola M Reid, Domenico Alvaro The biliary tree--a reservoir of multipotent stem cells. Nat Rev Gastroenterol Hepatol: 2012, 9(4);231-40 PubMed 22371217
Joshua R Friedman, Klaus H Kaestner On the origin of the liver. J. Clin. Invest.: 2011, 121(12);4630-3 PubMed 22105167
Rodolphe Carpentier, Regina Español Suñer, Noémi van Hul, Janel L Kopp, Jean-Bernard Beaudry, Sabine Cordi, Aline Antoniou, Peggy Raynaud, Sébastien Lepreux, Patrick Jacquemin, Isabelle A Leclercq, Maike Sander, Frédéric P Lemaigre Embryonic ductal plate cells give rise to cholangiocytes, periportal hepatocytes, and adult liver progenitor cells. Gastroenterology: 2011, 141(4);1432-8, 1438.e1-4 PubMed 21708104
Search Bookshelf Liver Development
Mall FP. A Study of the Structural Unit of the Liver (1906) Amer. J. of Anat. 5:227-308.
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Cite this page: Hill, M.A. (2015) Embryology Gastrointestinal Tract - Liver Development. Retrieved October 13, 2015, from https://embryology.med.unsw.edu.au/embryology/index.php/Gastrointestinal_Tract_-_Liver_Development
- © Dr Mark Hill 2015, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G