Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-745bb68f8f-v2bm5 Total loading time: 0 Render date: 2025-01-26T21:56:55.823Z Has data issue: false hasContentIssue false

Chapter 1 - Liver Development

from Section I - Pathophysiology of Pediatric Liver Disease

Published online by Cambridge University Press:  19 January 2021

By
Matthew C. Gillen  and
Stacey S. Huppert
Edited by
Frederick J. Suchy ,
Ronald J. Sokol  and
William F. Balistreri
Edited in association with
Jorge A. Bezerra ,
Cara L. Mack  and
Benjamin L. Shneider
Frederick J. Suchy
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Ronald J. Sokol
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
William F. Balistreri
Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Jorge A. Bezerra
Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Cara L. Mack
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Benjamin L. Shneider
Affiliation:
Texas Children’s Hospital, Houston
Get access

Summary

The essential liver endocrine and exocrine functions require a precise spatial arrangement of the repeated hepatic lobule consisting of the central vein, portal vein, hepatic artery, intrahepatic bile duct system, and hepatocyte zonation. This allows (1) blood to be carried through the liver parenchyma and sampled by all hepatocytes, (2) hepatocytes to uptake metabolites and toxins from the blood for metabolizing and detoxification from their basal sinusoidal side, and (3) hepatocytes to produce and secrete bile from their apical canalicular side to be carried out of the liver through the biliary (i.e., intrahepatic bile duct) system composed of biliary epithelial cells (i.e., cholangiocytes).

Type
Chapter
Information
Liver Disease in Children , pp. 1 - 11
Publisher: Cambridge University Press
Print publication year: 2021

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

El Sebae, GK, et al. Single-cell murine genetic fate mapping reveals bipotential hepatoblasts and novel multi-organ endoderm progenitors. Development 2018; 145(19). Published online October 11, 2018. doi:10.1242/dev.168658Google Scholar
Tremblay, KD, Zaret, KS. Distinct populations of endoderm cells converge to generate the embryonic liver bud and ventral foregut tissues. Dev Biol 2005;280(1):87–99.Google Scholar
Angelo, JR, Tremblay, KD. Laser-mediated cell ablation during post-implantation mouse development. Dev Dyn 2013;242(10):1202–9.Google Scholar
Huppert, SS, Iwafuchi-Doi, M. Molecular regulation of mammalian hepatic architecture. Curr Top Dev Biol 2019;132:91–136.Google Scholar
Lemaigre, FP. Development of the intrahepatic and extrahepatic biliary tract: a framework for understanding congenital diseases. Annu Rev Pathol 2019;15:1–22.Google Scholar
Schaub, JR, et al. De novo formation of the biliary system by TGF beta-mediated hepatocyte transdifferentiation. Nature 2018;557(7704):247–51.Google Scholar
Vestentoft, PS, et al. Three-dimensional reconstructions of intrahepatic bile duct tubulogenesis in human liver. BMC Dev Biol 2011;11:56.CrossRefGoogle ScholarPubMed
Tanimizu, N, Miyajima, A. Molecular mechanism of liver development and regeneration. Int Rev Cytol 2007;259:1–48.CrossRefGoogle ScholarPubMed
Deutsch, G, et al. A bipotential precursor population for pancreas and liver within the embryonic endoderm. Development 2001;128(6):871–81.CrossRefGoogle ScholarPubMed
Costa, RH, et al. Transcription factors in liver development, differentiation, and regeneration. Hepatology 2003;38(6):1331–47.CrossRefGoogle ScholarPubMed
Bort, R, et al. Hex homeobox gene controls the transition of the endoderm to a pseudostratified, cell emergent epithelium for liver bud development. Dev Biol 2006;290(1):44–56.CrossRefGoogle ScholarPubMed
Sosa-Pineda, B, Wigle, JT, Oliver, G. Hepatocyte migration during liver development requires Prox1. Nat Genet 2000;25(3):254–5.Google Scholar
Gerard, C, Tys, J, Lemaigre, FP. Gene regulatory networks in differentiation and direct reprogramming of hepatic cells. Semin Cell Dev Biol 2017;66:43–50.CrossRefGoogle ScholarPubMed
Wang, J, et al. FGF signaling is required for anterior but not posterior specification of the murine liver bud. Dev Dyn 2015;244(3):431–43.CrossRefGoogle Scholar
Parviz, F, et al. Hepatocyte nuclear factor 4 alpha controls the development of a hepatic epithelium and liver morphogenesis. Nat Genet 2003;34(3):292–6.Google Scholar
Wandzioch, E, Zaret, KS. Dynamic signaling network for the specification of embryonic pancreas and liver progenitors. Science 2009;324(5935):1707–10.CrossRefGoogle Scholar
Rossi, JM, et al. Distinct mesodermal signals, including BMPs from the septum transversum mesenchyme, are required in combination for hepatogenesis from the endoderm. Genes Dev 2001;15(15):1998–2009.Google Scholar
Palaria, A, et al. Patterning of the hepato-pancreatobiliary boundary by BMP reveals heterogeneity within the murine liver bud. Hepatology 2018;68(1):274–88.Google Scholar
Shih, HP, et al. A gene regulatory network cooperatively controlled by Pdx1 and Sox9 governs lineage allocation of foregut progenitor cells. Cell Rep 2015;13(2):326–36.Google Scholar
Matsumoto, K, et al. Liver organogenesis promoted by endothelial cells prior to vascular function. Science 2001;294(5542):559–63.Google Scholar
Camp, JG, et al. Multilineage communication regulates human liver bud development from pluripotency. Nature 2017;546(7659):533–8.CrossRefGoogle ScholarPubMed
Han, S, et al. Endothelial cells instruct liver specification of embryonic stem cell-derived endoderm through endothelial VEGFR2 signaling and endoderm epigenetic modifications. Stem Cell Res 2018;30:163–70.Google Scholar
Planas-Paz, L, et al. The RSPO-LGR4/5-ZNRF3/RNF43 module controls liver zonation and size. Nat Cell Biol 2016;18(5):467–79.Google Scholar
Huch, M, et al. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature 2013;494(7436):247–50.Google Scholar
Prior, N, et al. Lgr5(+) stem and progenitor cells reside at the apex of a heterogeneous embryonic hepatoblast pool. Development 2019;146(12). Published online June 12, 2019. doi:10.1242/dev.174557Google Scholar
Su, X, et al. Single-cell RNA-Seq analysis reveals dynamic trajectories during mouse liver development. BMC Genomics 2017;18(1):946.CrossRefGoogle ScholarPubMed
Tanimizu, N, et al. Isolation of hepatoblasts based on the expression of Dlk/Pref-1. J Cell Sci 2003;116(Pt 9):1775–86.Google Scholar
Yang, L, et al. A single-cell transcriptomic analysis reveals precise pathways and regulatory mechanisms underlying hepatoblast differentiation. Hepatology 2017;66(5):1387–1401.Google Scholar
Ludtke, TH, et al. Tbx3 promotes liver bud expansion during mouse development by suppression of cholangiocyte differentiation. Hepatology 2009;49(3):969–78.Google Scholar
Schmelzer, E, et al. Human hepatic stem cells from fetal and postnatal donors. J Exp Med 2007;204(8):1973–87.Google Scholar
Segal, JM, et al. Single cell analysis of human foetal liver captures the transcriptional profile of hepatobiliary hybrid progenitors. Nat Commun 2019;10(1):3350.CrossRefGoogle ScholarPubMed
Aizarani, N, et al. A human liver cell atlas reveals heterogeneity and epithelial progenitors. Nature 2019;572(7768):199–204.CrossRefGoogle ScholarPubMed
MacParland, SA, et al. Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations. Nat Commun 2018;9(1):4383.Google Scholar
Tarlow, BD, et al. Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes. Cell Stem Cell 2014;15(5):605–18.Google Scholar
Antoniou, A, et al. Intrahepatic bile ducts develop according to a new mode of tubulogenesis regulated by the transcription factor SOX9. Gastroenterology 2009;136(7):2325–33.Google Scholar
Raynaud, P, et al. A classification of ductal plate malformations based on distinct pathogenic mechanisms of biliary dysmorphogenesis. Hepatology 2011;53(6):1959–66.CrossRefGoogle ScholarPubMed
Benhamouche-Trouillet, S, et al. Proliferation-independent role of NF2 (merlin) in limiting biliary morphogenesis. Development 2018;145(9). Published online April 30, 2018. doi:10.1242/dev.162123Google Scholar
Takashima, Y, et al. Dynamic three-dimensional morphogenesis of intrahepatic bile ducts in mouse liver development. Hepatology 2015;61(3):1003–11.Google Scholar
Tanimizu, N, et al. Intrahepatic bile ducts are developed through formation of homogeneous continuous luminal network and its dynamic rearrangement in mice. Hepatology 2016;64(1):175–88.Google Scholar
Van Eyken, P, et al. The development of the intrahepatic bile ducts in man: a keratin-immunohistochemical study. Hepatology 1988;8(6):1586–95.CrossRefGoogle Scholar
Clotman, F, et al. Control of liver cell fate decision by a gradient of TGF beta signaling modulated by Onecut transcription factors. Genes Dev 2005;19(16):1849–54.CrossRefGoogle ScholarPubMed
Takayama, K, et al. CCAAT/enhancer binding protein-mediated regulation of TGFbeta receptor 2 expression determines the hepatoblast fate decision. Development 2014;141(1):91–100.Google Scholar
McDaniell, R, et al. NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway. Am J Hum Genet 2006;79(1):169–73.Google Scholar
Warthen, DM, et al. Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate. Hum Mutat 2006;27(5):436–43.Google Scholar
Jeliazkova, P, et al. Canonical Notch2 signaling determines biliary cell fates of embryonic hepatoblasts and adult hepatocytes independent of Hes1. Hepatology 2013;57(6):2469–79.Google Scholar
Sparks, EE, et al. Notch signaling regulates formation of the three-dimensional architecture of intrahepatic bile ducts in mice. Hepatology 2010;51(4):1391–400.Google Scholar
Thakurdas, SM, et al. Jagged1 heterozygosity in mice results in a congenital cholangiopathy which is reversed by concomitant deletion of one copy of Poglut1 (Rumi). Hepatology 2016;63(2):550–65.Google Scholar
Zong, Y, et al. Notch signaling controls liver development by regulating biliary differentiation. Development 2009;136(10):1727–39.Google Scholar
Yimlamai, D, et al. Hippo pathway activity influences liver cell fate. Cell 2014;157(6):1324–38.CrossRefGoogle ScholarPubMed
Zhang, N, et al. The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. Dev Cell 2010;19(1):27–38.Google Scholar
Tchorz, JS, et al. Notch2 signaling promotes biliary epithelial cell fate specification and tubulogenesis during bile duct development in mice. Hepatology 2009;50(3):871–9.Google Scholar
Wu, N, et al. The Hippo signaling functions through the Notch signaling to regulate intrahepatic bile duct development in mammals. Lab Invest 2017;97(7):843–53.Google Scholar
Desmet, VJ. Congenital diseases of intrahepatic bile ducts: variations on the theme “ductal plate malformation.” Hepatology 1992;16(4):1069–83.Google Scholar
Huppert, SS. A new set of classifications for ductal plate malformations. Hepatology 2011;53(6):1795–7.CrossRefGoogle ScholarPubMed
Carpentier, R, et al. Embryonic ductal plate cells give rise to cholangiocytes, periportal hepatocytes, and adult liver progenitor cells. Gastroenterology 2011;141(4):1432–8, 1438 e1–4.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×