Initiation of mammalian liver development from endoderm by fibroblast growth factors.

The signaling molecules that elicit embryonic induction of the liver from the mammalian gut endoderm or induction of other gut-derived organs are unknown. Close proximity of cardiac mesoderm, which expresses fibroblast growth factors (FGFs) 1, 2, and 8, causes the foregut endoderm to develop into the liver. Treatment of isolated foregut endoderm from mouse embryos with FGF1 or FGF2, but not FGF8, was sufficient to replace cardiac mesoderm as an inducer of the liver gene expression program, the latter being the first step of hepatogenesis. The hepatogenic response was restricted to endoderm tissue, which selectively coexpresses FGF receptors 1 and 4. Further studies with FGFs and their specific inhibitors showed that FGF8 contributes to the morphogenetic outgrowth of the hepatic endoderm. Thus, different FGF signals appear to initiate distinct phases of liver development during mammalian organogenesis.

[1]  S. Fukuda-Taira.  Hepatic induction in the avian embryo: specificity of reactive endoderm and inductive mesoderm. , 1981, Journal of embryology and experimental morphology.

[2]  B. Olwin,et al.  Repression of myogenic differentiation by aFGF, bFGF, and K-FGF is dependent on cellular heparan sulfate , 1992, The Journal of cell biology.

[3]  J. Darnell,et al.  Disruption of the HNF-4 gene, expressed in visceral endoderm, leads to cell death in embryonic ectoderm and impaired gastrulation of mouse embryos. , 1994, Genes & development.

[4]  H. Nogawa,et al.  Branching morphogenesis of embryonic mouse lung epithelium in mesenchyme-free culture. , 1995, Development.

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

[6]  C. MacArthur,et al.  Receptor Specificity of the Fibroblast Growth Factor Family* , 1996, The Journal of Biological Chemistry.

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

[8]  B. Hogan,et al.  Differential expression of multiple fork head related genes during gastrulation and axial pattern formation in the mouse embryo. , 1993, Development.

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

[10]  M. Barron,et al.  Developmental expression of fibroblast growth factor receptor‐1 (cek‐1; flg) during heart development , 1995, Developmental dynamics : an official publication of the American Association of Anatomists.

[11]  D. Goodman,et al.  An in situ-hybridization study of the localization of retinol-binding protein and transthyretin messenger RNAs during fetal development in the rat. , 1989, Differentiation; research in biological diversity.

[12]  G. Feldmann,et al.  Alpha fetoprotein and albumin gene transcripts are detected in distinct cell populations of the brain and kidney of the developing rat. , 1988, Differentiation; research in biological diversity.

[13]  M. Kirschner,et al.  Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in xenopus embryos , 1991, Cell.

[14]  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.

[15]  K Sigrist,et al.  GATA4 transcription factor is required for ventral morphogenesis and heart tube formation. , 1997, Genes & development.

[16]  M. Klagsbrun.  The fibroblast growth factor family: structural and biological properties. , 1989, Progress in growth factor research.

[17]  D. Hanahan,et al.  Precursor cells of mouse endocrine pancreas coexpress insulin, glucagon and the neuronal proteins tyrosine hydroxylase and neuropeptide Y, but not pancreatic polypeptide. , 1993, Development.

[18]  J. Smith,et al.  Responses of embryonic xenopus cells to activin and FGF are separated by multiple dose thresholds and correspond to distinct axes of the mesoderm , 1992, Cell.

[19]  Samuel L. Pfaff,et al.  Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells , 1997, Nature.

[20]  M. Sharpe,et al.  Scatter factor/hepatocyte growth factor is essential for liver development , 1995, Nature.

[21]  J. Rossant,et al.  HNF-3β is essential for node and notochord formation in mouse development , 1994, Cell.

[22]  J. Lough,et al.  Localization of bFGF-like proteins as punctate inclusions in the preseptation myocardium of the chicken embryo. , 1991, Developmental biology.

[23]  R. Balling,et al.  Antagonistic Interactions between FGF and BMP Signaling Pathways: A Mechanism for Positioning the Sites of Tooth Formation , 1997, Cell.

[24]  J. Rossant,et al.  fgfr-1 is required for embryonic growth and mesodermal patterning during mouse gastrulation. , 1994, Genes & development.

[25]  A. Schreiber,et al.  Heparin binds endothelial cell growth factor, the principal endothelial cell mitogen in bovine brain. , 1984, Science.

[26]  G. Martin,et al.  The mouse Fgf8 gene encodes a family of polypeptides and is expressed in regions that direct outgrowth and patterning in the developing embryo. , 1995, Development.

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

[28]  J. Lemire,et al.  Cell lineages and oval cell progenitors in rat liver development. , 1991, Cancer research.

[29]  M. Goldfarb,et al.  Fibroblast growth factor receptors have different signaling and mitogenic potentials , 1994, Molecular and cellular biology.

[30]  C. Deng,et al.  FGFR-3 and FGFR-4 function cooperatively to direct alveogenesis in the murine lung. , 1998, Development.

[31]  X. Zhu,et al.  Evidence that fibroblast growth factors 1 and 4 participate in regulation of cardiogenesis , 1996, Developmental dynamics : an official publication of the American Association of Anatomists.

[32]  W. Rutter,et al.  Onset of cell-specific gene expression in the developing mouse pancreas. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[33]  I. Thesleff,et al.  Expression and function of FGFs‐4, ‐8, and ‐9 suggest functional redundancy and repetitive use as epithelial signals during tooth morphogenesis , 1998, Developmental dynamics : an official publication of the American Association of Anatomists.

[34]  E. Wagner,et al.  c-Jun is essential for normal mouse development and hepatogenesis , 1993, Nature.

[35]  M. Scott,et al.  Homeotic genes regulate the spatial expression of putative growth factors in the visceral mesoderm of Drosophila embryos. , 1990, Development.

[36]  G. Martin,et al.  An Fgf8 mutant allelic series generated by Cre- and Flp-mediated recombination , 1998, Nature Genetics.

[37]  G. Martin,et al.  FGF-4 and BMP-2 have opposite effects on limb growth , 1993, Nature.

[38]  J M Slack,et al.  eFGF regulates Xbra expression during Xenopus gastrulation. , 1994, The EMBO journal.

[39]  C. MacArthur,et al.  Roles for FGF8 in the Induction, Initiation, and Maintenance of Chick Limb Development , 1996, Cell.

[40]  C H Fox,et al.  The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary. , 1996, Genes & development.

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

[42]  M. Capecchi,et al.  The role of Hoxa-3 in mouse thymus and thyroid development. , 1995, Development.

[43]  T. Jessell,et al.  Integrated FGF and BMP signaling controls the progression of progenitor cell differentiation and the emergence of pattern in the embryonic anterior pituitary. , 1998, Development.

[44]  P. Lawrence,et al.  Induction across germ layers in Drosophila mediated by a genetic cascade , 1990, Cell.

[45]  J. Rossant,et al.  The transcription factor HNF3beta is required in visceral endoderm for normal primitive streak morphogenesis. , 1998, Development.