Talk:Gastrointestinal Tract - Liver Development: Difference between revisions

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==2010==
==2010==
===Embryology of the biliary tract===
Dig Surg. 2010;27(2):87-9. Epub 2010 Jun 10.
Ando H.
Source
Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan. hando@med.nagoya-u.ac.jp
Abstract
A hepatic diverticulum appears in the ventral wall of the primitive midgut early in the 4th week of intrauterine life in the development of the human embryo. This small diverticulum is the anlage for the development of the liver, extrahepatic biliary ducts, gallbladder, and ventral pancreas. By the 5th week, all elements of the biliary tree are recognizable. Marked elongation of the common duct occurs with plugging of the lumen by epithelial cells. Recanalization of the lumen of the common duct starts at the end of the 5th week and moves slowly distally. By the 6th week, the common duct and ventral pancreatic bud rotate 180 degrees clockwise around the duodenum. Early in the 7th week, the bile and pancreatic ducts end in closed cavities of the duodenum. Between the early 8th and 12th week, hepatopancreatic ducts have both superior and inferior orifices. Of these two orifices, the inferior one is usually suppressed. The muscle of the sphincter of Oddi develops from a concentric ring of mesenchyme surrounding the preampullary portion of the bile and pancreatic ducts. At about the 10th week, the muscle of the sphincter of Oddi undergoes differentiation. In the 16th week, the muscularis propria extends from just outside the fenestra to the upper end of the ampulla. By the 28th week, the musculus proprius is differentiated almost to the distal end of the ampulla.
(c) 2010 S. Karger AG, Basel.
PMID: 20551648


===Sinusoid development and morphogenesis may be stimulated by VEGF-Flk-1 signaling during fetal mouse liver development===
===Sinusoid development and morphogenesis may be stimulated by VEGF-Flk-1 signaling during fetal mouse liver development===

Revision as of 00:58, 4 May 2011

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Cite this page: Hill, M.A. (2024, March 28) Embryology Gastrointestinal Tract - Liver Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Gastrointestinal_Tract_-_Liver_Development

2010

Embryology of the biliary tract

Dig Surg. 2010;27(2):87-9. Epub 2010 Jun 10.

Ando H. Source Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan. hando@med.nagoya-u.ac.jp

Abstract

A hepatic diverticulum appears in the ventral wall of the primitive midgut early in the 4th week of intrauterine life in the development of the human embryo. This small diverticulum is the anlage for the development of the liver, extrahepatic biliary ducts, gallbladder, and ventral pancreas. By the 5th week, all elements of the biliary tree are recognizable. Marked elongation of the common duct occurs with plugging of the lumen by epithelial cells. Recanalization of the lumen of the common duct starts at the end of the 5th week and moves slowly distally. By the 6th week, the common duct and ventral pancreatic bud rotate 180 degrees clockwise around the duodenum. Early in the 7th week, the bile and pancreatic ducts end in closed cavities of the duodenum. Between the early 8th and 12th week, hepatopancreatic ducts have both superior and inferior orifices. Of these two orifices, the inferior one is usually suppressed. The muscle of the sphincter of Oddi develops from a concentric ring of mesenchyme surrounding the preampullary portion of the bile and pancreatic ducts. At about the 10th week, the muscle of the sphincter of Oddi undergoes differentiation. In the 16th week, the muscularis propria extends from just outside the fenestra to the upper end of the ampulla. By the 28th week, the musculus proprius is differentiated almost to the distal end of the ampulla.

(c) 2010 S. Karger AG, Basel.

PMID: 20551648

Sinusoid development and morphogenesis may be stimulated by VEGF-Flk-1 signaling during fetal mouse liver development

Dev Dyn. 2010 Feb;239(2):386-97.

Sugiyama Y, Takabe Y, Nakakura T, Tanaka S, Koike T, Shiojiri N.

Department of Biology, Faculty of Science, Shizuoka University, Shizuoka City, Japan.

Abstract Early morphogenesis of hepatic sinusoids was histochemically and experimentally analyzed, and the importance of VEGF-Flk-1 signaling in the vascular development was examined during murine liver organogenesis. FITC-gelatin injection experiments into young murine fetuses demonstrated that all primitive sinusoidal structures were confluent with portal and central veins, suggesting that hepatic vessel development may occur via angiogenesis. At 12.5-14.5 days of gestation, VEGF receptors designated Flk-1, especially their mature form, were highly expressed in endothelial cells of primitive sinusoidal structures and highly phosphorylated on their tyrosine residues. At the same time, VEGF was also detected in hepatoblasts/hepatocytes, hemopoietic cells, and megakaryocytes of the whole liver parenchyma. Furthermore, the addition of VEGF to E12.5 liver cell cultures significantly induced the growth and branching morphogenesis of sinusoidal endothelial cells. Therefore, VEGF-Flk-1 signaling may play an important role in the growth and morphogenesis of primitive sinusoids during fetal liver development.

PMID: 19918884

2009

Dynamic signaling network for the specification of embryonic pancreas and liver progenitors

Science. 2009 Jun 26;324(5935):1707-10.

Wandzioch E, Zaret KS. Source Cell and Developmental Biology Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA. Abstract Studies of the formation of pancreas and liver progenitors have focused on individual inductive signals and cellular responses. Here, we investigated how bone morphogenetic protein, transforming growth factor-beta (TGFbeta), and fibroblast growth factor signaling pathways converge on the earliest genes that elicit pancreas and liver induction in mouse embryos. The inductive network was found to be dynamic; it changed within hours. Different signals functioned in parallel to induce different early genes, and two permutations of signals induced liver progenitor domains, which revealed flexibility in cell programming. Also, the specification of pancreas and liver progenitors was restricted by the TGFbeta pathway. These findings may enhance progenitor cell specification from stem cells for biomedical purposes and can help explain incomplete programming in stem cell differentiation protocols.

PMID: 19556507 http://www.ncbi.nlm.nih.gov/pubmed/19556507

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771431


Notch signaling controls liver development by regulating biliary differentiation

Development. 2009 May;136(10):1727-39. Epub 2009 Apr 15.

Zong Y, Panikkar A, Xu J, Antoniou A, Raynaud P, Lemaigre F, Stanger BZ. Source Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Abstract

In the mammalian liver, bile is transported to the intestine through an intricate network of bile ducts. Notch signaling is required for normal duct formation, but its mode of action has been unclear. Here, we show in mice that bile ducts arise through a novel mechanism of tubulogenesis involving sequential radial differentiation. Notch signaling is activated in a subset of liver progenitor cells fated to become ductal cells, and pathway activation is necessary for biliary fate. Notch signals are also required for bile duct morphogenesis, and activation of Notch signaling in the hepatic lobule promotes ectopic biliary differentiation and tubule formation in a dose-dependent manner. Remarkably, activation of Notch signaling in postnatal hepatocytes causes them to adopt a biliary fate through a process of reprogramming that recapitulates normal bile duct development. These results reconcile previous conflicting reports about the role of Notch during liver development and suggest that Notch acts by coordinating biliary differentiation and morphogenesis.

PMID: 19369401 http://www.ncbi.nlm.nih.gov/pubmed/19369401

2004

Spiegel's lobe bile ducts often drain into the right hepatic duct or its branches: study using drip-infusion cholangiography-computed tomography in 179 consecutive patients

World J Surg. 2004 Oct;28(10):1001-6. Epub 2004 Sep 29.

Kitami M, Murakami G, Ko S, Takase K, Tuboi M, Saito H, Nakajima Y, Takahashi S.

Department of Diagnostic Radiology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, 980-8574, Sendai, Japan. Abstract Using drip-infusion cholangiography-computed tomography (DIC-CT), we successfully identified the bile ducts draining the caudate lobe in 138 of 179 consecutive patients with extrahepatic cholelithiasis (179 ducts from Spiegel's lobe and 154 from the paracaval portion; 1-5 ducts per patient). The dorsal subsegmental duct of S8 (B8c) was often identified and could be discriminated from the paracaval caudate ducts, thus acting as a landmark for the right margin of the caudate lobe. Notably, in more than one-third of the 138 patients, at least one of the Spiegel's lobe ducts drained into the right hepatic duct or its branches (30.2% of the 179 ducts overall; all ducts joined branches of the right lobe in 25 patients). Similarly, 34.4% of the 154 paracaval caudate lobe ducts drained into the left hepatic duct or its branches. These "anatomical left/right dissociations" between the drainage territory and route were much more frequent than previously reported. Our results confirm the effectiveness of DIC-CT as a classical, noninvasive method for presurgical evaluation of the biliary system, but they also suggest that anatomical partial resection of the dorsal liver in patients with hilar cholangioma is often impossible because of contralateral biliary drainage.

PMID: 15573255

Approximately 6,000 liver transplant operations are performed in the United States (http://www.liverfoundation.org/education/info/transplant/) and 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), but these numbers are limited by the availability of donor organs.

Original Page

http://embryology.med.unsw.edu.au/Notes/git7.htm

http://www.ncbi.nlm.nih.gov/pubmed/20169088

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821762/?tool=pubmed

File:Gitbpmsm.gif 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. This structure grows rapidly.
File:PigD3L.GIF Stage 13 embryo, the transverse septum then 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 th eliver primordium.
File:HumE6L.GIF Stage 22 embryo, the rapidly developing liver 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.

Page Links: [#Intro Introduction] | [#Recent Some Recent Findings] | [#LiverDevelopmentStages Liver Development Stages] | [#table Components of Liver Formation] | [#ductalplate Ductal Plate] | [#bile_secretion Bile Secretion] | [#intrahepatic_bile_ducts Intrahepatic Bile Ducts] | [#HepaticStemCells Hepatic Stem Cells] | [#Kupffer Kupffer Cells] | [#Molecular Liver Molecular] | [#HepaticTranscriptionFactors Hepatic Transcription Factors] | [#Abnormalities Abnormalities] | [#References References] | [#Glossary Glossary]

Some Recent Findings

Hong S-K, Dawid IB (2008) Alpha2 Macroglobulin-Like Is Essential for Liver Development in Zebrafish. PLoS ONE 3(11): e3736. doi:10.1371/journal.pone.0003736

"This report on Alpha 2 Macroglobulin (A2ML) function in zebrafish development provides the first evidence for a specific role of an A2M family gene in liver formation during early embryogenesis in a vertebrate."

Hart SN, Cui Y, Klaassen CD, Zhong XB, THREE PATTERNS OF CYTOCHROME P450 GENE EXPRESSION DURING LIVER MATURATION IN MICE. Drug Metab Dispos. 2008 Oct 9.

"To systematically examine the ontogenic gene expression patterns of cytochrome P450 genes (Cyps) in mice… the developmental expression of Cyps in (neonatal) mouse liver can be divided into three patterns, suggesting different mechanisms responsible for the expression of Cyps during liver maturation."

This paper in Drug Metabolism Dispos describes how the newborn liver continues to differentiate postnatally. Remember that just because the organ looks like the mature form, does not mean that it yet functions like the adult organ. This may also relate to the changes that occur in human postnatal drug clearance rates.

Huang H, Ruan H, Aw MY, Hussain A, Guo L, Gao C, Qian F, Leung T, Song H, Kimelman D, Wen Z, Peng J. Mypt1-mediated spatial positioning of Bmp2-producing cells is essential for liver organogenesis. Development. 2008 Oct;135(19):3209-18.

"Mesodermal tissues produce various inductive signals essential for morphogenesis of endodermal organs. ...Our results demonstrate that myosin phosphatase targeting subunit 1 (Mypt1) mediates coordination between mesoderm and endoderm cell movements in order to carefully position the liver primordium such that it receives a Bmp signal that is essential for liver formation in zebrafish."

Fabris L, Cadamuro M, Libbrecht L, Raynaud P, Spirlì C, Fiorotto R, Okolicsanyi L, Lemaigre F, Strazzabosco M, Roskams T. Epithelial expression of angiogenic growth factors modulate arterial vasculogenesis in human liver development. Hepatology. 2008 Feb;47(2):719-28.

"The reciprocal expression of angiogenic growth factors and receptors during development supports their involvement in the cross talk between liver epithelial cells and the portal vasculature. Cholangiocytes generate a VEGF gradient that is crucial during the migratory stage, when it determines arterial vasculogenesis in their vicinity, whereas angiopoietin-1 signaling from hepatoblasts contributes to the remodeling of the hepatic artery necessary to meet the demands of the developing epithelium."

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."

Sadler KC, Krahn KN, Gaur NA, Ukomadu C. Liver growth in the embryo and during liver regeneration in zebrafish requires the cell cycle regulator, uhrf1. Proc Natl Acad Sci U S A. 2007 Jan 22

"Zebrafish uhrf1 (ubiquitin-like protein containing PHD and ring finger domains-1, Np95 in mouse, ICBP90 in human) is a cell cycle regulator and transcriptional activator of top2a expression required for liver outgrowth in both the embryo and adult."

Hepatic Stem Cells

Hepatoblasts are bipotential in that they can differentiate as either hepatocytes or cholangiocytes (bile duct cells). There are currently a number of different species bipotential hepatic stem cells available for liver development research.

Mouse - HBC-3, H-CFU-C, MMH and BMEL

Rat - rhe14321

Primate - IPFLS (Oncogene Paper)

Search PubMed Now: hepatoblasts

Kupffer Cells

File:Kupffer.jpg 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.

Naito M, Hasegawa G, Ebe Y, Yamamoto T. Differentiation and function of Kupffer cells. Med Electron Microsc. 2004 Mar;37(1):16-28.

Kupffer Cells(Image: Blue Histology)
 

Search PubMed Now: Kupffer cell development

Intrahepatic Bile Ducts

Intrahepatic bile ducts (IHBDs) transport bile secreted from hepatocytes to the hepatic duct and are are lined with biliary epithelial cells (BECs, cholangiocytes). Biliary epithelial cells are generated from the bipotent hepatoblasts surrounding the portal vein.

Cholangiocyte Cells

Bile duct epithelial cell derived from hepatoblasts during embryonic liver development. These cells line the bile duct system and have apical cilia extending into the intrahepatic bile duct lumen.

Cholangiocytes function (mechano-, osmo-, and chemo-sensory) to regulate the fluidity and alkalinity of canalicular bile by reabsorptive and secretory events adjusting the final secreted bile composition.

Abnormalities associated with cholangiocyte cell development or function are called cholangiociliopathies.(polycystin-1, polycystin-2, and fibrocystin).

Search PubMed Now: Cholangiocyte cell development

Liver Molecular

Hepatic Transcription Factors

The following combination of transcription factors appear to be invoved in hepatic differentiation and growth program.

Homeobox gene (Hhex) multiple stages of hepatobiliary development.

Variant homeodomain-containing proteins (HNF-1 alpha, HNF-1 beta)

Winged helix family proteins HNF-3 alpha, HNF-3 beta, and HNF-3 gamma (also called FoxA1, 2, and 3)

Nuclear hormone receptor family (HNF-4, COUP-TFII, LRH-1, FXR alpha, and PXR)

Basic leucine zipper-containing factor C/EBP alpha

Onecut homeodomain protein HNF-6

Ubiquitin-like protein containing PHD and ring finger domains-1,uhrf1 in zebrafish (also called Np95 in mouse, ICBP90 in human)

4-5 weeks - liver consists of a few hepatic cords. Hematopoietic cell or blood cells were undetectable in the 4 week of gestation.

5 weeks - population of cells arise (larger, rounded) expressing VEGFA, flt-4 and Tie-2 proteins.

6 weeks - flk-1 transiently expressed.

7 weeks - greatest number of VEGFA, flt-4 and Tie-2 protein immunopositive cells.

11-12 weeks - expression decreased.

7-12 weeks - hepatic cells express VEGF-C and flt-1

Angiopoietin-1, angiopoietin-2 and Tie-2 were detectable on those cells which expressed VEGFA, flt-4 and Tie-2 from weeks 5 to 12 of gestation. The expression of angiopoietin-1 and angiopoietin-2 were weakly and Tie-2 was strongly.

All factors and their receptors were undetectable on vascular endothelial cells at 4-12 weeks of gestation.

Patterns of VEGF family on cells of liver are different before and after 7 weeks of gestation. The hematopoiesis in fetal liver may be related to development of hepatic cell.

Liver Vascular Development

Vascular Endothelial Growth Factor (VEGF) - from developing bile duct cholangiocytes regulate arterial vasculogenesis.

angiopoietin-1 - from hepatoblasts regulates remodeling of the hepatic artery.

Human Liver Gene Expression

4-5 weeks - liver consists of a few hepatic cords. Hematopoietic cell or blood cells were undetectable in the 4 week of gestation.

5 weeks - population of cells arise (larger, rounded) expressing VEGFA, flt-4 and Tie-2 proteins.

6 weeks - flk-1 transiently expressed.

7 weeks - greatest number of VEGFA, flt-4 and Tie-2 protein immunopositive cells.

11-12 weeks - expression decreased.

7-12 weeks - hepatic cells express VEGF-C and flt-1

Angiopoietin-1, angiopoietin-2 and Tie-2 were detectable on those cells which expressed VEGFA, flt-4 and Tie-2 from weeks 5 to 12 of gestation. The expression of angiopoietin-1 and angiopoietin-2 were weakly and Tie-2 was strongly. (Human Liver Gene Expression Data from: Mei Y, Li AD, Jiang JY, Zhou HY, Yang HJ, Yang SX, Hong HR, Song HR.[Expression of VEGFA, VEGFC, angiopoietin-1, angiopoietin-2 and their receptors on development liver during gestation of weeks 3-12 of human embryo.]Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2004 Oct;12(5):632-6. Chinese.)

Abnormalities

Both liver and biliary tract developmental abnormalities can lead to severe liver disease.

Ductal Plate Malformations

Interlobular bile ducts- autosomal recessive polycystic kidney disease

Smaller interlobular ducts- von Meyenburg complexes

Larger intrahepatic bile ducts- Caroli's disease

Cholangiociliopathies - abnormalities in cholangiocyte cells in intrahepatic bile ducts either their development or function. Can be associated with the development of the apical cilia (polycystin-1, polycystin-2, and fibrocystin).

Obstetric cholestasis - (or intrahepatic cholestasis of pregnancy) remains widely disregarded as an important clinical problem, with many obstetricians still considering its main symptom, pruritus (itching), a natural association of pregnancy. Obstetric cholestasis is associated with cholesterol gallstones. It may be extremely stressful for the mother but also carries risks for the baby. Piotr Milkiewicz, Elwyn Elias, Catherine Williamson, and Judith Weaver

Milkiewicz P, Elias E, Williamson C, Weaver J. Obstetric cholestasis. BMJ. 2002 Jan 19;324(7330):123-4. BMJ Link

Alagille syndrome (AGS) - a disorder characterized by few intrahepatic bile ducts. A paper suggests that Notch signaling has a role in biliary epithelial cell differentiation and subsequent tubular formation during IHBD development.

Kodama Y, Hijikata M, Kageyama R, Shimotohno K, Chiba T. The role of notch signaling in the development of intrahepatic bile ducts. Gastroenterology. 2004 Dec;127(6):1775-86.

References

Huang H, Ruan H, Aw MY, Hussain A, Guo L, Gao C, Qian F, Leung T, Song H, Kimelman D, Wen Z, Peng J. Mypt1-mediated spatial positioning of Bmp2-producing cells is essential for liver organogenesis. Development. 2008 Oct;135(19):3209-18.

Fabris L, Cadamuro M, Libbrecht L, Raynaud P, Spirlì C, Fiorotto R, Okolicsanyi L, Lemaigre F, Strazzabosco M, Roskams T. Epithelial expression of angiogenic growth factors modulate arterial vasculogenesis in human liver development. Hepatology. 2008 Feb;47(2):719-28.

Naito M, Hasegawa G, Ebe Y, Yamamoto T. Differentiation and function of Kupffer cells. Med Electron Microsc. 2004 Mar;37(1):16-28.

Delalande JM, Milla PJ, Burns AJ. Hepatic nervous system development. Anat Rec A Discov Mol Cell Evol Biol. 2004 Sep;280(1):848-53.

Kinoshita T, Miyajima A. Cytokine regulation of liver development. Biochim Biophys Acta. 2002 Nov 11;1592(3):303-12.

Crawford JM. Development of the intrahepatic biliary tree. Semin Liver Dis. 2002 Aug;22(3):213-26.

Duncan SA. Transcriptional regulation of liver development. Dev Dyn. 2000 Oct;219(2):131-42.

Shiojiri N. Development and differentiation of bile ducts in the mammalian liver. Microsc Res Tech. 1997 Nov 15;39(4):328-35.

Darlington GJ. Molecular mechanisms of liver development and differentiation. Curr Opin Cell Biol. 1999 Dec;11(6):678-82.

Costa RH, Kalinichenko VV, Holterman AX, Wang X. Transcription factors in liver development, differentiation, and regeneration. Hepatology. 2003 Dec;38(6):1331-47.

Watt AJ, Garrison WD, Duncan SA. HNF4: a central regulator of hepatocyte differentiation and function. Hepatology. 2003 Jun;37(6):1249-53.

Shen CN, Horb ME, Slack JM, Tosh D. Transdifferentiation of pancreas to liver. Mech Dev. 2003 Jan;120(1):107-16.

Strick-Marchand H, Weiss MC. Embryonic liver cells and permanent lines as models for hepatocyte and bile duct cell differentiation. Mech Dev. 2003 Jan;120(1):89-98.

Search PubMed Now: hepatic development | liver development | gall bladder development |

Earlier References

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    • Excellent earlier review on liver development. (source for references cited below)
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