Gastrointestinal Tract - Liver Development
- 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 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.
Sonia C Garcia Caraballo, Tine M Comhair, Cornelis H C Dejong, Wouter H Lamers, S Eleonore Köhler A high-protein diet is anti-steatotic and has no pro-inflammatory side effects in dyslipidaemic APOE2 knock-in mice. Br. J. Nutr.: 2014;1-15 PMID:25160499 Jolana Cermanova, Zuzana Kadova, Eva Dolezelova, Marie Zagorova, Vaclav Safka, Milos Hroch, Tomas Laho, Magdalena Holeckova, Jaroslav Mokry, Petra Kovarikova, Jan Bures, Martin Sterba, Stanislav Micuda Deferoxamine but not dexrazoxane alleviates liver injury induced by endotoxemia in rats. Shock: 2014; PMID:25140599 Banu Mansuroğlu, Serap Derman, Aylin Yaba, Kadriye Kızılbey Protective Effect of Chemically Modified SOD on Lipid Peroxidation and Antioxidant Status in Diabetic Rats. Int. J. Biol. Macromol.: 2014; PMID:25124383 Ling Lu, Qin Lan, Zhiyuan Li, Xiaohui Zhou, Jian Gu, Qiang Li, Julie Wang, Maogen Chen, Ya Liu, Yi Shen, David D Brand, Bernhard Ryffel, David A Horwitz, Francisco P Quismorio, Zhongmin Liu, Bin Li, Nancy J Olsen, Song Guo Zheng Critical role of all-trans retinoic acid in stabilizing human natural regulatory T cells under inflammatory conditions. Proc. Natl. Acad. Sci. U.S.A.: 2014; PMID:25099355 Mai Thi Nhu Tran, Junko Tanaka, Michito Hamada, Yuka Sugiyama, Shota Sakaguchi, Megumi Nakamura, Satoru Takahashi, Yoshihiro Miwa In Vivo image Analysis Using iRFP Transgenic Mice. Exp. Anim.: 2014, 63(3);311-319 PMID:25077761
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
(More? 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 | Flash movies | Quicktime movies
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 | Flash movies | Quicktime 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 PMID:21943389
- Ewa Wandzioch, Kenneth S Zaret Dynamic signaling network for the specification of embryonic pancreas and liver progenitors. Science: 2009, 324(5935);1707-10 PMID: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 PMID: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 PMID: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 PMID: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 PMID:9718390
- 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 PMID: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 PMID:19841744 | PMC2760133 | PLoS
- James M Crawford Development of the intrahepatic biliary tree. Semin. Liver Dis.: 2002, 22(3);213-26 PMID:12360416
- Makoto Naito, Go Hasegawa, Yusuke Ebe, Takashi Yamamoto Differentiation and function of Kupffer cells. Med Electron Microsc: 2004, 37(1);16-28 PMID: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 PMID: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 PMID:21199531
Hisami Ando Embryology of the biliary tract. Dig Surg: 2010, 27(2);87-9 PMID: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 PMID:20169172
Karim Si-Tayeb, Frédéric P Lemaigre, Stephen A Duncan Organogenesis and development of the liver. Dev. Cell: 2010, 18(2);175-89 PMID: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 PMID:20086072
T Roskams, V Desmet Embryology of extra- and intrahepatic bile ducts, the ductal plate. Anat Rec (Hoboken): 2008, 291(6);628-35 PMID: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; PMID:22371217
Joshua R Friedman, Klaus H Kaestner On the origin of the liver. J. Clin. Invest.: 2011, 121(12);4630-3 PMID: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 PMID:21708104
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Cite this page: Hill, M.A. (2014) Embryology Gastrointestinal Tract - Liver Development. Retrieved August 28, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Gastrointestinal_Tract_-_Liver_Development
- © Dr Mark Hill 2014, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G