Talk:Gastrointestinal Tract - Gallbladder Development

From Embryology
About Discussion Pages  
Mark Hill.jpg
On this website the Discussion Tab or "talk pages" for a topic has been used for several purposes:
  1. References - recent and historic that relates to the topic
  2. Additional topic information - currently prepared in draft format
  3. Links - to related webpages
  4. Topic page - an edit history as used on other Wiki sites
  5. Lecture/Practical - student feedback
  6. Student Projects - online project discussions.
Links: Pubmed Most Recent | Reference Tutorial | Journal Searches

Glossary Links

Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link

Cite this page: Hill, M.A. (2024, May 20) Embryology Gastrointestinal Tract - Gallbladder Development. Retrieved from


Anatomy of rodent and human livers: What are the differences?

Biochim Biophys Acta Mol Basis Dis. 2018 May 26. pii: S0925-4439(18)30189-3. doi: 10.1016/j.bbadis.2018.05.019. [Epub ahead of print]

Kruepunga N1, Hakvoort TBM2, Hikspoors JPJM1, Köhler SE1, Lamers WH3.

Abstract The size of the liver of terrestrial mammals obeys the allometric scaling law over a weight range of >3 ∗ 106. Since scaling reflects adaptive changes in size or scale among otherwise similar animals, we can expect to observe more similarities than differences between rodent and human livers. Obvious differences, such as the presence (rodents) or absence (humans) of lobation and the presence (mice, humans) or absence (rats) of a gallbladder, suggest qualitative differences between the livers of these species. After review, however, we conclude that these dissimilarities represent relatively small quantitative differences. The microarchitecture of the liver is very similar among mammalian species and best represented by the lobular concept, with the biggest difference present in the degree of connective tissue development in the portal tracts. Although larger mammals have larger lobules, increasing size of the liver is mainly accomplished by increasing the number of lobules. The increasing role of the hepatic artery in lobular perfusion of larger species is, perhaps, the most important and least known difference between small and large livers, because it profoundly affects not only interventions like liver transplantations, but also calculations of liver function. Copyright © 2018. Published by Elsevier B.V. KEYWORDS: Allometry; Gallbladder; Hepatic artery; Lobes; Lobules; Portal vein PMID: 29842921 DOI: 10.1016/j.bbadis.2018.05.019


The fate of the vitelline and umbilical veins during the development of the human liver

J Anat. 2017 Nov;231(5):718-735. doi: 10.1111/joa.12671. Epub 2017 Aug 8.

Hikspoors JPJM1, Peeters MMJP1, Mekonen HK1, Kruepunga N1, Mommen GMC1, Cornillie P2, Köhler SE1,3, Lamers WH1,4.


Differentiation of endodermal cells into hepatoblasts is well studied, but the remodeling of the vitelline and umbilical veins during liver development is less well understood. We compared human embryos between 3 and 10 weeks of development with pig and mouse embryos at comparable stages, and used Amira 3D reconstruction and Cinema 4D remodeling software for visualization. The vitelline and umbilical veins enter the systemic venous sinus on each side via a common entrance, the hepatocardiac channel. During expansion into the transverse septum at Carnegie Stage (CS)12 the liver bud develops as two dorsolateral lobes or 'wings' and a single ventromedial lobe, with the liver hilum at the intersection of these lobes. The dorsolateral lobes each engulf a vitelline vein during CS13 and the ventromedial lobe both umbilical veins during CS14, but both venous systems remain temporarily identifiable inside the liver. The dominance of the left-sided umbilical vein and the rightward repositioning of the sinuatrial junction cause de novo development of left-to-right shunts between the left umbilical vein in the liver hilum and the right hepatocardiac channel (venous duct) and the right vitelline vein (portal sinus), respectively. Once these shunts have formed, portal branches develop from the intrahepatic portions of the portal vein on the right side and the umbilical vein on the left side. The gall bladder is a reliable marker for this hepatic vascular midline. We found no evidence for large-scale fragmentation of embryonic veins as claimed by the 'vestigial' theory. Instead and in agreement with the 'lineage' theory, the vitelline and umbilical veins remained temporally identifiable inside the liver after being engulfed by hepatoblasts. In agreement with the 'hemodynamic' theory, the left-right shunts develop de novo. KEYWORDS: liver bud; liver primordium; portal vein; sinusoids; umbilical vein; venous duct; venous sinus; vitelline vein PMID: 28786203 DOI: 10.1111/joa.12671


Fate mapping of gallbladder progenitors in posteroventral foregut endoderm of mouse early somite-stage embryos

J Vet Med Sci. 2015 Jan 7.

Uemura M1, Igarashi H, Ozawa A, Tsunekawa N, Kurohmaru M, Kanai-Azuma M, Kanai Y.


In early embryogenesis, the posteroventral foregut endoderm gives rise to the budding endodermal organs including the liver, ventral pancreas and gallbladder during early somitogenesis. Despite the detailed fate maps of the liver and pancreatic progenitors in the mouse foregut endoderm, the exact location of the gallbladder progenitors remains unclear. In this study, we performed a DiI fate-mapping analysis using whole-embryo cultures of mouse early somite-stage embryos. Here, we show that the majority of gallbladder progenitors in 9-11-somite-stage embryos are located in the lateral-most domain of the foregut endoderm at the first intersomite junction level along the anteroposterior axis. This definition of their location highlights a novel entry point to understanding of the molecular mechanisms of initial specification of the gallbladder.

PMID 25648459


Biliary differentiation and bile duct morphogenesis in development and disease

Int J Biochem Cell Biol. 2011 Feb;43(2):245-56. Epub 2009 Sep 6.

Raynaud P, Carpentier R, Antoniou A, Lemaigre FP. Source Université catholique de Louvain, de Duve Institute, Brussels, Belgium.


The biliary tract consists of a network of intrahepatic and extrahepatic ducts that collect and drain the bile produced by hepatocytes to the gut. The bile ducts are lined by cholangiocytes, a specialized epithelial cell type that has a dual origin. Intrahepatic cholangiocytes derive from the liver precursor cells, whereas extrahepatic cholangiocytes are generated directly from the endoderm. In this review we discuss the mechanisms of cholangiocyte differentiation and bile duct morphogenesis, and describe how developing ducts interact with the hepatic artery. We also present an overview of the mechanisms of biliary dysgenesis in humans.

Copyright © 2009 Elsevier Ltd. All rights reserved.

PMID 19735739


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.


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

Muscularis mucosae versus muscularis propria in gallbladder, cystic duct, and common bile duct: smoothelin and desmin immunohistochemical study

Ann Diagn Pathol. 2010 Dec;14(6):408-12. Epub 2010 Sep 22.

Raparia K, Zhai QJ, Schwartz MR, Shen SS, Ayala AG, Ro JY. Source Department of Pathology, The Methodist Hospital, Weill Medical College, Cornell University, Houston, TX 77030, USA.


The muscle layer in the cystic duct and common bile duct is not well defined, and it is unresolved whether it represents muscularis mucosae or muscularis propria. Smoothelin is a novel smooth muscle-specific contractile protein expressed only in fully differentiated smooth muscle cells of the muscularis propria and not in proliferative or noncontractile smooth muscle cells of the muscularis mucosae. In this study, we characterize the histologic aspects of the muscle layer in gallbladder, cystic duct, and common bile duct by evaluation of routine histologic sections and the utilization of immunohistochemistry using desmin and smoothelin. Formalin-fixed, paraffin-embedded sections of the gallbladder (15 cases), cystic duct (11 cases), and common bile duct (10 cases) were stained for smoothelin and desmin. Staining intensity was evaluated as weak or strong. The staining pattern score was evaluated as follows: 0 or negative = less than or equal to 5% positivity, +1 or focal = 6% to 10% positivity, +2 or moderate = 11% to 50% positivity, and +3 = greater than 50% muscle cells positivity. With desmin, strong and diffuse (+3) staining was observed in all gallbladder cases (15/15, 100%), highlighting one continuous muscle layer. The muscle layer was discontinuous and interrupted in all cystic duct cases and in most common bile ducts, highlighted by the desmin stain. Smoothelin intensely stained (at least +2) muscle fibers in the gallbladder in 11 (73%) of 15 cases similar to that observed with desmin staining. In contrast, common bile ducts predominantly had absent or weak and focal immunostaining (0 or +1 staining) with smoothelin (7/10, 70%), with only a few cases (3/10, 30%) having +2 staining (no cases with +3). Cystic ducts also showed absent or weak and focal immunostaining with smoothelin, with 5 (44%) of 11 cases showing 2+ immunostaining with smoothelin (no cases with 3+). Based on our findings, we conclude that, in the gallbladder wall, the muscle layer is muscularis propria and there is no muscularis mucosae present. In the cystic duct and common bile duct, only an attenuated and incomplete muscle layer of muscularis mucosae is present; because there is no muscularis propria, there probably is limited contractile function. Differentiating these anatomical muscle structures may be important for the pathologic staging of carcinoma in these organs.

Copyright © 2010 Elsevier Inc. All rights reserved.

PMID: 21074688


Embryology of extra- and intrahepatic bile ducts, the ductal plate

Anat Rec (Hoboken). 2008 Jun;291(6):628-35.

Roskams T, Desmet V. Source Department of Morphology and Molecular Pathology, University of Leuven, Leuven, Belgium.


In the human embryo, the first anlage of the bile ducts and the liver is the hepatic diverticulum or liver bud. For up to 8 weeks of gestation, the extrahepatic biliary tree develops through lengthening of the caudal part of the hepatic diverticulum. This structure is patent from the beginning and remains patent and in continuity with the developing liver at all stages. The hepatic duct (ductus hepaticus) develops from the cranial part (pars hepatica) of the hepatic diverticulum. The distal portions of the right and left hepatic ducts develop from the extrahepatic ducts and are clearly defined tubular structures by 12 weeks of gestation. The proximal portions of the main hilar ducts derive from the first intrahepatic ductal plates. The extrahepatic bile ducts and the developing intrahepatic biliary tree maintain luminal continuity from the very start of organogenesis throughout further development, contradicting a previous study in the mouse suggesting that the extrahepatic bile duct system develops independently from the intrahepatic biliary tree and that the systems are initially discontinuous but join up later. The normal development of intrahepatic bile ducts requires finely timed and precisely tuned epithelial-mesenchymal interactions, which proceed from the hilum of the liver toward its periphery along the branches of the developing portal vein. Lack of remodeling of the ductal plate results in the persistence of an excess of embryonic bile duct structures remaining in their primitive ductal plate configuration. This abnormality has been termed the ductal plate malformation.

PMID 18484608


Induced biliary excretion of Listeria monocytogenes

Infect Immun. 2006 Mar;74(3):1819-27.

Hardy J, Margolis JJ, Contag CH.

SourceDepartment of Pediatrics, E150 Clark Center MC 5427, Stanford University School of Medicine, Stanford, CA 94305, USA. AbstractListeria monocytogenes is a ubiquitous gram-positive bacterium that can cause systemic and often life-threatening disease in immunocompromised hosts. This organism is largely an intracellular pathogen; however, we have determined that it can also grow extracellularly in animals, in the lumen of the gallbladder. The significance of growth in the gallbladder with respect to the pathogenesis and spread of listeriosis depends on the ability of the bacterium to leave this organ and be disseminated to other tissues and into the environment. Should this process be highly inefficient, growth in the gallbladder would have no impact on pathogenesis or spread, but if it occurs efficiently, bacterial growth in this organ may contribute to listeriosis and dissemination of this organism. Here, we use whole-body imaging to determine the efficacy and kinetics of food- and hormone-induced biliary excretion of L. monocytogenes from the murinegallbladder, demonstrating that transit through the bile duct into the intestine can occur within 5 min of induction of gallbladder contraction by food or cholecystokinin and that movement of bacteria through the intestinal lumen can occur very rapidly in the absence of fecal material. These studies demonstrate that L. monocytogenes bacteria replicating in the gallbladder can be expelled from the organ efficiently and that the released bacteria move into the intestinal tract, where they pass into the environment and may possibly reinfect the animal.

PMID 16495556


Agenesis of the gallbladder: difficulties in management

J Gastroenterol Hepatol. 2005 May;20(5):671-5.

Bani-Hani KE. Source Department of Surgery, King Abdullah University Hospital, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan.


Gallbladder agenesis is a rare congenital biliary anomaly that may be associated with other biliary and extrabiliary congenital anomalies. Awareness of this entity by clinicians and radiologists is essential because many of these patients present with biliary symptoms and have unnecessary operations. In the present article, the relative epidemiological, etiological (embryology and development), pathophysiological, diagnostic tools and pitfalls and management aspects of this rare anatomic anomaly are briefly discussed through review of the literature. Particular reference to the difficulty in preoperative diagnosis is highlighted. The importance of the possibility of preoperative diagnosis to avoid unnecessary surgery is stressed.

PMID 15853977


Development of the intrahepatic biliary tree

Semin Liver Dis. 2002 Aug;22(3):213-26.

Crawford JM. Source Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida 32610-0275, USA.


The liver develops from two anlages: the hepatic diverticulum, which buds off the ventral side of the foregut, and the septum transversum, which is the mesenchymal plate that partially separates the embryonic thoracic and abdominal cavities. The endodermal cells of the hepatic diverticulum invade the septum transversum, forming sheets and cords of hepatoblasts arrayed along the sinusoidal vascular channels derived from the vitelline veins emanating from the yolk sac. The vitelline veins fuse to form the portal vein, which ramifies as tributaries within the liver along mesenchymal channels termed portal tracts. Those hepatoblasts immediately adjacent to the mesenchyme of the portal tracts differentiate into a ductal plate, a single circumferential layer of biliary epithelial cells. Mesenchymal cells interpose between the ductal plate and the remaining parenchymal hepatoblasts, which differentiate into hepatocytes. By week 7 the ductal plate begins to reduplicate, forming a double layer of cells around the portal tract. Lumena form between the two cell layers of the ductal plate, forming peripheral biliary tubular structures. These peripheral tubules remodel and, with continued proliferation of the mesenchyme, by the 11th week begin to become more centrally located within portal tracts as terminal bile ducts with a circular cross-section. The remaining ductal plate resorbs, leaving behind only tethers of bile ductules connecting the terminal bile ducts to the parenchyma. Abutting and within the parenchyma are the canals of Hering, ductular structures half-lined by hepatocytes and half-lined by biliary epithelial cells. Maturation of the intrahepatic biliary tree to the mature tubular treelike architecture occurs from the hilum of the liver outward, beginning around the 11th week of gestation and continuing past birth for several months. The architecture of maturation is the same regardless of gestational age or radial location in the liver. Importantly, the immature intrahepatic biliary system maintains patency and continuity with the extrahepatic biliary tree throughout gestation, with no evidence of a solid phase of development. Thus, from the earliest time of hepatocellular bile formation beginning around the 12th week, there is a patent passage to the alimentary canal.

PMID 12360416