Organogenesis and development of the liver.

Embryonic development of the liver has been studied intensely, yielding insights that impact diverse areas of developmental and cell biology. Understanding the fundamental mechanisms that control hepatogenesis has also laid the basis for the rational differentiation of stem cells into cells that display many hepatic functions. Here, we review the basic molecular mechanisms that control the formation of the liver as an organ.

[1]  Ryoichiro Kageyama,et al.  Control of endodermal endocrine development by Hes-1 , 2000, Nature Genetics.

[2]  J. Scoazec,et al.  Structural and functional differentiation of sinusoidal endothelial cells during liver organogenesis in humans. , 1996, Blood.

[3]  G. Rousseau,et al.  The transcription factor hepatocyte nuclear factor-6 controls the development of pancreatic ducts in the mouse. , 2006, Gastroenterology.

[4]  Christine K. C. Loo,et al.  Origin of stellate cells from submesothelial cells in a developing human liver , 2008, Liver international : official journal of the International Association for the Study of the Liver.

[5]  K. Jungermann,et al.  Functional specialization of different hepatocyte populations. , 1989, Physiological reviews.

[6]  B. Spear,et al.  Hereditary persistence of alpha-fetoprotein and H19 expression in liver of BALB/cJ mice is due to a retrovirus insertion in the Zhx2 gene. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[7]  F. Tronche,et al.  Intrahepatic bile ducts develop according to a new mode of tubulogenesis regulated by the transcription factor SOX9. , 2009, Gastroenterology.

[8]  M. Masu,et al.  Conversion of biliary system to pancreatic tissue in Hes1-deficient mice , 2004, Nature Genetics.

[9]  N. Copeland,et al.  Mouse oncostatin M: an immediate early gene induced by multiple cytokines through the JAK‐STAT5 pathway. , 1996, The EMBO journal.

[10]  D. Rockey,et al.  Endothelin receptors in rat liver: lipocytes as a contractile target for endothelin 1. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[11]  L. Jin,et al.  Transcriptional control in the mammalian liver: liver development, perinatal repression, and zonal gene regulation , 2006, Cellular and Molecular Life Sciences CMLS.

[12]  J. A. Guadix,et al.  Contribution of mesothelium‐derived cells to liver sinusoids in avian embryos , 2004, Developmental dynamics : an official publication of the American Association of Anatomists.

[13]  T. Yatskievych,et al.  Regulation of Hex gene expression and initial stages of avian hepatogenesis by Bmp and Fgf signaling. , 2004, Developmental biology.

[14]  C. Gandhi,et al.  Wnt'er in liver: Expression of Wnt and frizzled genes in mouse , 2007, Hepatology.

[15]  H. Aburatani,et al.  Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. , 2005, Genomics.

[16]  Y. Sugiyama,et al.  Immunolocalization of extracellular matrix components and integrins during mouse liver development , 2004, Hepatology.

[17]  F. Lemaigre Notch signaling in bile duct development: New insights raise new questions , 2008, Hepatology.

[18]  C. Basilico,et al.  Compensation by Fibroblast Growth Factor 1 (FGF1) Does Not Account for the Mild Phenotypic Defects Observed in FGF2 Null Mice , 2000, Molecular and Cellular Biology.

[19]  N. LaRusso,et al.  Cholangiociliopathies: genetics, molecular mechanisms and potential therapies , 2009, Current opinion in gastroenterology.

[20]  R. Fisher,et al.  Human hepatocyte transplantation: worldwide results. , 2006, Transplantation.

[21]  G. Rousseau,et al.  The Onecut transcription factors HNF-6/OC-1 and OC-2 regulate early liver expansion by controlling hepatoblast migration. , 2007, Developmental biology.

[22]  Nicola J. Rinaldi,et al.  Control of Pancreas and Liver Gene Expression by HNF Transcription Factors , 2004, Science.

[23]  E. Morrisey,et al.  GATA6 Is Essential for Embryonic Development of the Liver but Dispensable for Early Heart Formation , 2005, Molecular and Cellular Biology.

[24]  K. Zaret,et al.  GATA transcription factors as potentiators of gut endoderm differentiation. , 1998, Development.

[25]  N. Hastie,et al.  Wt1 and retinoic acid signaling are essential for stellate cell development and liver morphogenesis. , 2007, Developmental biology.

[26]  J. Friedman,et al.  The microRNA-30 family is required for vertebrate hepatobiliary development. , 2009, Gastroenterology.

[27]  T. Roskams,et al.  The onecut transcription factor HNF6 is required for normal development of the biliary tract. , 2002, Development.

[28]  K. Zaret,et al.  Initiation of mammalian liver development from endoderm by fibroblast growth factors. , 1999, Science.

[29]  Yan Zhou,et al.  Haploinsufficiency of the Mouse Forkhead Box f1 Gene Causes Defects in Gall Bladder Development* , 2002, The Journal of Biological Chemistry.

[30]  H. Nakauchi,et al.  Sall4 regulates cell fate decision in fetal hepatic stem/progenitor cells. , 2009, Gastroenterology.

[31]  L. Denson,et al.  HNF3beta and GATA-4 transactivate the liver-enriched homeobox gene, Hex. , 2000, Gene.

[32]  F. Endo,et al.  FGF signaling segregates biliary cell‐lineage from chick hepatoblasts cooperatively with BMP4 and ECM components in vitro , 2008, Developmental dynamics : an official publication of the American Association of Anatomists.

[33]  Richard C Trembath,et al.  Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane fusion, cause arthrogryposis–renal dysfunction–cholestasis (ARC) syndrome , 2004, Nature Genetics.

[34]  K. Zaret Genetic programming of liver and pancreas progenitors: lessons for stem-cell differentiation , 2008, Nature Reviews Genetics.

[35]  J. C. Belmonte,et al.  Tbx 3 controls the fate of hepatic progenitor cells in liver development by suppressing p 19 ARF expression , 2022 .

[36]  L. Samson,et al.  A microscale in vitro physiological model of the liver: predictive screens for drug metabolism and enzyme induction. , 2005, Current drug metabolism.

[37]  Douarin Nm An experimental analysis of liver development. , 1975 .

[38]  T. Tanaka,et al.  Homeobox gene Hex is essential for onset of mouse embryonic liver development and differentiation of the monocyte lineage. , 2000, Biochemical and biophysical research communications.

[39]  Kjetil H Elvevold,et al.  The liver sinusoidal endothelial cell: a cell type of controversial and confusing identity. , 2008, American journal of physiology. Gastrointestinal and liver physiology.

[40]  R. Beddington,et al.  Hex homeobox gene-dependent tissue positioning is required for organogenesis of the ventral pancreas , 2004, Development.

[41]  K. Kaestner The making of the liver: developmental competence in foregut endoderm and induction of the hepatogenic program. , 2005, Cell cycle.

[42]  J. I. Izpisúa Belmonte,et al.  Tbx3 controls the fate of hepatic progenitor cells in liver development by suppressing p19ARF expression , 2008, Development.

[43]  G. Michalopoulos,et al.  Wnt impacts growth and differentiation in ex vivo liver development. , 2004, Experimental cell research.

[44]  S. Duncan,et al.  Mammalian hepatocyte differentiation requires the transcription factor HNF-4alpha. , 2000, Genes & development.

[45]  N. L. Douarin Synthèse du glycogène dans les hépatocytes en voie de différenciation: rôle des mésenchymes homologue et hétérologues , 1968 .

[46]  B. Spear,et al.  Position-dependent activity of alpha -fetoprotein enhancer element III in the adult liver is due to negative regulation. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[47]  M. Manns,et al.  Multi-stage analysis of differential gene expression in BALB/C mouse liver development by high-density microarrays. , 2003, Differentiation; research in biological diversity.

[48]  R. Jain,et al.  LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis. , 2001, Cancer research.

[49]  Sridhar Hannenhalli,et al.  The evolution of Fox genes and their role in development and disease , 2009, Nature Reviews Genetics.

[50]  S. Matsuzaki,et al.  An endothelin A receptor antagonist induces dilatation of sinusoidal endothelial fenestrae: implications for endothelin-1 in hepatic microcirculation , 2007, Journal of Gastroenterology.

[51]  F. Lemaigre Mechanisms of liver development: concepts for understanding liver disorders and design of novel therapies. , 2009, Gastroenterology.

[52]  J. Neuberger,et al.  A Bioartificial Liver--State of the Art , 2002, Science.

[53]  K. Zaret,et al.  A bipotential precursor population for pancreas and liver within the embryonic endoderm. , 2001, Development.

[54]  Klaus H. Kaestner,et al.  The initiation of liver development is dependent on Foxa transcription factors , 2005, Nature.

[55]  J. R. Coleman,et al.  Hepatic specification of the gut endoderm in vitro: cell signaling and transcriptional control. , 1996, Genes & development.

[56]  M. Nemer,et al.  Transcriptional activation of BMP-4 and regulation of mammalian organogenesis by GATA-4 and -6. , 2003, Developmental biology.

[57]  M. Grompe Principles of therapeutic liver repopulation , 2006, Journal of Inherited Metabolic Disease.

[58]  N. LaRusso,et al.  MicroRNA15a modulates expression of the cell-cycle regulator Cdc25A and affects hepatic cystogenesis in a rat model of polycystic kidney disease. , 2008, The Journal of clinical investigation.

[59]  Aarati R. Ranade,et al.  Robust expansion of human hepatocytes in Fah−/−/Rag2−/−/Il2rg−/− mice , 2007, Nature Biotechnology.

[60]  L. Gresh,et al.  Bile system morphogenesis defects and liver dysfunction upon targeted deletion of HNF1beta. , 2002, Development.

[61]  Kenneth J. Hillan,et al.  Angiogenesis-Independent Endothelial Protection of Liver: Role of VEGFR-1 , 2003, Science.

[62]  M. Bhatia,et al.  Analysis of the human fetal liver hematopoietic microenvironment. , 2005, Stem cells and development.

[63]  Colin A. Johnson,et al.  Summary Zebrafish vps 33 b , an ortholog of the gene responsible for human arthrogryposis-renal dysfunction-cholestasis syndrome , regulates biliary development downstream of the onecut transcription factor hnf 6 , 2005 .

[64]  M. Adams,et al.  Recent advances in the molecular pathology, cell biology and genetics of ciliopathies , 2008, Journal of Medical Genetics.

[65]  G. Konopka,et al.  Hepatocyte nuclear factor 4 (cid:1) orchestrates expression of cell adhesion proteins during the epithelial transformation of the developing liver , 2006 .

[66]  S. Duncan,et al.  Development of the mammalian liver and ventral pancreas is dependent on GATA4 , 2007, BMC Developmental Biology.

[67]  S. Curbishley,et al.  Human hepatic sinusoidal endothelial cells can be distinguished by expression of phenotypic markers related to their specialised functions in vivo. , 2006, World journal of gastroenterology.

[68]  J. Rossant,et al.  Liver Organogenesis Promoted by Endothelial Cells Prior to Vascular Function , 2001, Science.

[69]  F. Tronche,et al.  Plasticity and expanding complexity of the hepatic transcription factor network during liver development. , 2006, Genes & development.

[70]  M. Tomizawa,et al.  Suppression of C/EBPα expression in periportal hepatoblasts may stimulate biliary cell differentiation through increased Hnf6 and Hnf1b expression , 2006, Development.

[71]  福田 晃久 Ectopic pancreas formation in Hes1 knockout mice reveals plasticity of endodermal progenitors of the gut, bile duct, and pancreas , 2007 .

[72]  J. Ruijter,et al.  Hepatic HNF4α deficiency induces periportal expression of glutamine synthetase and other pericentral enzymes , 2007, Hepatology.

[73]  R. Suzuki,et al.  Establishment of a hepatocytic epithelial cell line from the murine fetal liver capable of promoting hemopoietic cell proliferation , 1993, Journal of cellular physiology.

[74]  A. Dobierzewska,et al.  The oncofetal gene glypican 3 is regulated in the postnatal liver by zinc fingers and homeoboxes 2 and in the regenerating liver by alpha‐fetoprotein regulator 2 , 2007, Hepatology.

[75]  Uma M. Muthurajan,et al.  Nucleosome-binding affinity as a primary determinant of the nuclear mobility of the pioneer transcription factor FoxA. , 2009, Genes & development.

[76]  P. Courtoy,et al.  Control of liver cell fate decision by a gradient of TGF beta signaling modulated by Onecut transcription factors. , 2005, Genes & development.

[77]  K. Zaret,et al.  Hex homeobox gene controls the transition of the endoderm to a pseudostratified, cell emergent epithelium for liver bud development. , 2006, Developmental biology.

[78]  Colin A. Johnson,et al.  Zebrafish vps33b, an ortholog of the gene responsible for human arthrogryposis-renal dysfunction-cholestasis syndrome, regulates biliary development downstream of the onecut transcription factor hnf6. , 2005, Development.

[79]  E. Wisse,et al.  An ultrastructural characterization of the endothelial cell in the rat liver sinusoid under normal and various experimental conditions, as a contribution to the distinction between endothelial and Kupffer cells. , 1972, Journal of ultrastructure research.

[80]  T. Lints,et al.  Hlx homeo box gene is essential for an inductive tissue interaction that drives expansion of embryonic liver and gut. , 1996, Genes & development.

[81]  K. Kaestner In the zone: how a hepatocyte knows where it is. , 2009, Gastroenterology.

[82]  Ken Matsumoto,et al.  Wnt9a secreted from the walls of hepatic sinusoids is essential for morphogenesis, proliferation, and glycogen accumulation of chick hepatic epithelium. , 2008, Developmental biology.

[83]  B. Cieply,et al.  β‐Catenin deletion in hepatoblasts disrupts hepatic morphogenesis and survival during mouse development , 2008, Hepatology.

[84]  D. Stainier,et al.  Bmp and Fgf signaling are essential for liver specification in zebrafish , 2007, Development.

[85]  G. Michalopoulos,et al.  Beta-catenin antisense studies in embryonic liver cultures: role in proliferation, apoptosis, and lineage specification. , 2003, Gastroenterology.

[86]  M. Strazzabosco Foxa1 and Foxa2 regulate bile duct development in mice. , 2010, Journal of hepatology.

[87]  K. Zaret,et al.  Distinct populations of endoderm cells converge to generate the embryonic liver bud and ventral foregut tissues. , 2005, Developmental biology.

[88]  John E. Le Lay,et al.  Hepatic function is preserved in the absence of mature microRNAs , 2009, Hepatology.

[89]  L. Zon,et al.  APC mutant zebrafish uncover a changing temporal requirement for wnt signaling in liver development. , 2008, Developmental biology.

[90]  T. Pieler,et al.  Cell-autonomous and signal-dependent expression of liver and intestine marker genes in pluripotent precursor cells from Xenopus embryos , 2003, Mechanisms of Development.

[91]  Yoshiaki Ito,et al.  Fetal liver development requires a paracrine action of oncostatin M through the gp130 signal transducer , 1999, The EMBO journal.

[92]  K. Zaret,et al.  Hepatocyte differentiation initiates during endodermal-mesenchymal interactions prior to liver formation. , 1991, Development.

[93]  Y. Ito,et al.  Hepatic differentiation induced by oncostatin M attenuates fetal liver hematopoiesis. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[94]  Jerrold M. Ward,et al.  Hepatocyte Nuclear Factor 4α (Nuclear Receptor 2A1) Is Essential for Maintenance of Hepatic Gene Expression and Lipid Homeostasis , 2001, Molecular and Cellular Biology.

[95]  I. Verma,et al.  Repopulation of adult and neonatal mice with human hepatocytes: A chimeric animal model , 2007, Proceedings of the National Academy of Sciences.

[96]  I. Krantz,et al.  NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway. , 2006, American journal of human genetics.

[97]  P. Henriet,et al.  Role of metalloproteinases at the onset of liver development , 2008, Development, growth & differentiation.

[98]  S. Burley,et al.  Binding of the winged‐helix transcription factor HNF3 to a linker histone site on the nucleosome , 1998, The EMBO journal.

[99]  Colin C. Collins,et al.  Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1 , 1997, Nature Genetics.

[100]  H. Hara,et al.  FINE STRUCTURE OF HEPATIC SINUSOIDS and THEIR DEVELOPMENT IN HUMAN EMBRYOS and FETUSES , 1983, Acta pathologica japonica.

[101]  D. Stainier,et al.  Mesodermal Wnt2b signalling positively regulates liver specification , 2006, Nature.

[102]  M. Menger,et al.  Loss of NF-κB activation in Kupffer cell-depleted mice impairs liver regeneration after partial hepatectomy , 2007 .

[103]  P. Mazur,et al.  Liver‐specific inactivation of Notch2, but not Notch1, compromises intrahepatic bile duct development in mice , 2008, Hepatology.

[104]  S. Friedman Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. , 2008, Physiological reviews.

[105]  Andreas Reimann,et al.  A transcriptional network in polycystic kidney disease , 2004, The EMBO journal.

[106]  L. Carlsson,et al.  Lhx2 is expressed in the septum transversum mesenchyme that becomes an integral part of the liver and the formation of these cells is independent of functional Lhx2. , 2004, Gene expression patterns : GEP.

[107]  T. Evans,et al.  Gata4 regulates the formation of multiple organs , 2005, Development.

[108]  D. Rickman,et al.  Stabilization of β‐catenin affects mouse embryonic liver growth and hepatoblast fate , 2007, Hepatology.

[109]  E. Medlock,et al.  The liver hemopoietic environment: I. Developing hepatocytes and their role in fetal hemopoiesis , 1983, The Anatomical record.

[110]  R. Kageyama,et al.  The role of notch signaling in the development of intrahepatic bile ducts. , 2004, Gastroenterology.

[111]  S. Duncan,et al.  GATA4 is essential for formation of the proepicardium and regulates cardiogenesis. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[112]  K. Zaret,et al.  An early developmental transcription factor complex that is more stable on nucleosome core particles than on free DNA. , 1999, Molecular cell.

[113]  E. Houssaint Differentiation of the mouse hepatic primordium. I. An analysis of tissue interactions in hepatocyte differentiation. , 1980, Cell differentiation.

[114]  M. Yaniv,et al.  Hepatocyte Nuclear Factor 1 Inactivation Results in Hepatic Dysfunction, Phenylketonuria, and Renal Fanconi Syndrome , 1996, Cell.

[115]  J. Wells,et al.  Different thresholds of fibroblast growth factors pattern the ventral foregut into liver and lung , 2004, Development.

[116]  D. Tosh,et al.  The Wnt/β‐catenin pathway: master regulator of liver zonation? , 2006 .

[117]  G. Ramadori,et al.  Mesenchymal origin of hepatic stellate cells, submesothelial cells, and perivascular mesenchymal cells during mouse liver development , 2009, Hepatology.

[118]  Paul S. Meltzer,et al.  Mutations in the human Jagged1 gene are responsible for Alagille syndrome , 1997, Nature Genetics.

[119]  A. Miyajima,et al.  Development of murine hepatic sinusoidal endothelial cells characterized by the expression of hyaluronan receptors , 2007, Developmental dynamics : an official publication of the American Association of Anatomists.

[120]  E R Weibel,et al.  Distribution of Organelles and Membranes between Hepatocytes and Nonhepatocytes in a Stereological Study , 2022 .

[121]  D. Kioussis,et al.  The homeobox gene Hex is required in definitive endodermal tissues for normal forebrain, liver and thyroid formation. , 2000, Development.

[122]  B. Hogan,et al.  Distinct mesodermal signals, including BMPs from the septum transversum mesenchyme, are required in combination for hepatogenesis from the endoderm. , 2001, Genes & development.

[123]  R. Evans,et al.  RXR alpha mutant mice establish a genetic basis for vitamin A signaling in heart morphogenesis. , 1994, Genes & development.

[124]  B. Stanger,et al.  Notch signaling controls liver development by regulating biliary differentiation , 2009, Development.

[125]  J. Adamson,et al.  Hepatocyte nuclear factor 4α controls the development of a hepatic epithelium and liver morphogenesis , 2003, Nature Genetics.

[126]  D. Rickman,et al.  Apc tumor suppressor gene is the "zonation-keeper" of mouse liver. , 2006, Developmental cell.

[127]  Frank R. Lin,et al.  Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4. , 2002, Molecular cell.

[128]  S. Schneider-Maunoury,et al.  Crucial role of vHNF1 in vertebrate hepatic specification , 2008, Development.

[129]  K. Zaret,et al.  Dynamic Signaling Network for the Specification of Embryonic Pancreas and Liver Progenitors , 2009, Science.

[130]  Michael P Hunter,et al.  The homeobox gene Hhex is essential for proper hepatoblast differentiation and bile duct morphogenesis. , 2007, Developmental biology.

[131]  A. Zorn,et al.  Repression of Wnt/β-catenin signaling in the anterior endoderm is essential for liver and pancreas development , 2007, Development.

[132]  K. Kaestner,et al.  The mouse Forkhead Box m1 transcription factor is essential for hepatoblast mitosis and development of intrahepatic bile ducts and vessels during liver morphogenesis. , 2004, Developmental biology.

[133]  K. Kaestner,et al.  Sox17 regulates organ lineage segregation of ventral foregut progenitor cells. , 2009, Developmental cell.

[134]  Guillermo Oliver,et al.  Hepatocyte migration during liver development requires Prox1 , 2000, Nature Genetics.

[135]  S. Goerdt,et al.  Wnt2 acts as a cell type–specific, autocrine growth factor in rat hepatic sinusoidal endothelial cells cross‐stimulating the VEGF pathway , 2008, Hepatology.

[136]  J. Scoazec,et al.  Vascular Development and Differentiation During Human Liver Organogenesis , 2008, Anatomical record.

[137]  O. Sansom,et al.  Liver zonation occurs through a beta-catenin-dependent, c-Myc-independent mechanism. , 2009, Gastroenterology.

[138]  H. Schouten,et al.  Kupffer cell depletion by CI2MDP-liposomes alters hepatic cytokine expression and delays liver regeneration after partial hepatectomy. , 2000, Liver.

[139]  K. Kaestner,et al.  The Foxa family of transcription factors in development and metabolism , 2006, Cellular and Molecular Life Sciences CMLS.

[140]  E. Darai,et al.  Expression of integrins during liver organogenesis in humans , 1998, Hepatology.

[141]  M. Menger,et al.  Loss of NF-kappaB activation in Kupffer cell-depleted mice impairs liver regeneration after partial hepatectomy. , 2007, American journal of physiology. Gastrointestinal and liver physiology.

[142]  Nicholas F LaRusso,et al.  Cholangiocyte primary cilia in liver health and disease , 2008, Developmental dynamics : an official publication of the American Association of Anatomists.

[143]  M. Barton,et al.  Zinc finger protein ZBTB20 is a key repressor of alpha-fetoprotein gene transcription in liver , 2008, Proceedings of the National Academy of Sciences.

[144]  T. Roskams,et al.  Hepatic artery malformations associated with a primary defect in intrahepatic bile duct development. , 2003, Journal of hepatology.

[145]  R. Kageyama,et al.  Ectopic pancreas formation in Hes1 -knockout mice reveals plasticity of endodermal progenitors of the gut, bile duct, and pancreas. , 2006, The Journal of clinical investigation.

[146]  Takashi Yamamoto,et al.  SERIES : Hepatic sinusoidal cells in liver physiology and pathology , 2004 .

[147]  K. Kaestner,et al.  An FGF response pathway that mediates hepatic gene induction in embryonic endoderm cells. , 2006, Developmental cell.

[148]  T. Alonzi,et al.  Convergence of Wnt signaling on the HNF4alpha-driven transcription in controlling liver zonation. , 2009, Gastroenterology.