title: Progressive developmental restriction, acquisition of left-right identity and cell growth behavior during lobe formation in mouse liver development.
abstract: To identify cell-based decisions implicated in morphogenesis of the mammalian liver, we performed clonal analysis of hepatocytes/hepatoblasts in mouse liver development, using a knock-in allele of Hnf4a/laacZ This transgene randomly undergoes a low frequency of recombination that generates a functional lacZ gene that produces β-galactosidase in tissues in which Hnf4a is expressed. Two types of β-galactosidase-positive clones were found. Most have undergone three to eight cell divisions and result from independent events (Luria-Delbrück fluctuation test); we calculate that they arose between E8.5 and E13.5. A second class was mega-clones derived from early endoderm progenitors, generating many descendants. Some originated from multi-potential founder cells, with labeled cells in the liver, pancreas and/or intestine. A few mega-clones populate only one side of the liver, indicating hepatic cell chirality. The patterns of labeled cells indicate cohesive and often oriented growth, notably in broad radial stripes, potentially implicated in the formation of liver lobes. This retrospective clonal analysis gives novel insights into clonal origins, cell behavior of progenitors and distinct properties of endoderm cells that underlie the formation and morphogenesis of the liver.
authors.affiliation: CNRS URA 2578, Département Biologie du Développement et Cellules Souches, Institut Pasteur, 25-28 rue du Dr Roux, Paris 75724, Cedex 15, France mweiss@pasteur.fr.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Weiss
authors.affiliation: Imagine-Institut Pasteur, Heart Morphogenesis Group, Paris 75015, France.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Le Garrec
authors.affiliation: CNRS URA 2578, Département Biologie du Développement et Cellules Souches, Institut Pasteur, 25-28 rue du Dr Roux, Paris 75724, Cedex 15, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Coqueran
authors.affiliation: Innate Immunity Unit, INSERM U668, Institut Pasteur, Paris 75724, France.
authors.forename: Helene
authors.initials: H
authors.lastname: Strick-Marchand
authors.affiliation: CNRS URA 2578, Département Biologie du Développement et Cellules Souches, Institut Pasteur, 25-28 rue du Dr Roux, Paris 75724, Cedex 15, France.
authors.forename: Margaret
authors.initials: M
authors.lastname: Buckingham
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D055879:Gene Knock-In Techniques; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics*; D022781:Hepatocytes / Q000166:cytology*; D007763:Lac Operon / Q000235:genetics; D008099:Liver / Q000196:embryology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D038081:Organogenesis / Q000502:physiology*; D012189:Retrospective Studies; D013234:Stem Cells / Q000166:cytology; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D051557:Hepatocyte Nuclear Factor 4; C496593:Hnf4a protein, mouse; D001616:beta-Galactosidase
keywords: Hnf4a-directed expression; Mouse liver development; Retrospective clonal analysis; β-Galactosidase reporter