Abstract
ABSTRACT The HNF-3 α, β and γ genes constitute a family of transcription factors that are required for hepatocytespecific gene expression of a number of genes, e.g. transthyretin, α-1 antitrypsin and tyrosine aminotransferase. These genes share a highly conserved DNA-binding domain first found in the Drosophila gene, forkhead, which is required for the normal patterning of the developing gut and central nervous system in Drosophila. In adult mouse tissues, transcripts from HNF-3 αand β have been localised to the liver, intestine and lung, whereas HNF-3 γ is found in the liver, intestine and testis. In light of the early developmental significance of forkhead in Drosophila, we have compared the patterns of expression of HNF-3 α, β and γ mRNAs during murine embryogenesis. We find that these genes are sequentially activated during development in the definitive endoderm. HNF-3 β mRNA is expressed in the node at the anterior end of the primitive streak in all three germ layers and is the first gene of this family to be activated. Subsequently, HNF-3 α is transcribed in the primitive endoderm in the region of the invaginating foregut and HNF-3 γ appears upon hindgut differentiation. These genes have different anterior boundaries of mRNA expression in the developing endoderm and transcripts are found in all endoderm-derived structures that differentiate posterior to this boundary. Therefore, we propose that these genes define regionalisation within the definitive endoderm. Furthermore, differential mRNA expression of HNF-3 α and β is detected in cells of the ventral neural epithelium, chordamesoderm and notochord. In the neural epithelium, expression of HNF-3 αand β mRNA becomes localised to cells of the floor plate. We propose that, in addition to their characterised requirement for liver-specific gene expression, HNF-3 αand γ are required for mesoderm and neural axis formation. We also conclude that HNF-3 β is the true orthologue of the Drosophila forkhead gene.
References
74
Referenced
414
10.1101/gad.4.3.372
/ Genes Dev / HNF-1 shares three sequence motifs with the POU domain proteins and is identical to LF-B1 and APF by Baumhueter (1990){'key': '2024121723182011500_DEVELOP_119_3_567C2', 'first-page': '87', 'article-title': 'An autoradiographic analysis of the potency of embryonic ectoderm in the 8th day postimplantation mouse embryo', 'volume': '64', 'author': 'Beddington', 'year': '1981', 'journal-title': 'J. Embryol. Exp. Morph'}
/ J. Embryol. Exp. Morph / An autoradiographic analysis of the potency of embryonic ectoderm in the 8th day postimplantation mouse embryo by Beddington (1981){'key': '2024121723182011500_DEVELOP_119_3_567C3', 'first-page': '265', 'article-title': 'An autoradiographic analysis of tissue potency in different regions of the embryonic ectoderm during gastrulation in the mouse', 'volume': '69', 'author': 'Beddington', 'year': '1982', 'journal-title': 'J. Embryol. Exp. Morph'}
/ J. Embryol. Exp. Morph / An autoradiographic analysis of tissue potency in different regions of the embryonic ectoderm during gastrulation in the mouse by Beddington (1982){'key': '2024121723182011500_DEVELOP_119_3_567C4', 'first-page': '61', 'article-title': 'Use of chimeras to study gene function in mesodermal tissues during gastrulation and early organogenesis.In Postimplantation Development in the Mouse', 'volume-title': 'Ciba Found Symp', 'author': 'Beddington', 'year': '1992'}
/ Ciba Found Symp / Use of chimeras to study gene function in mesodermal tissues during gastrulation and early organogenesis.In Postimplantation Development in the Mouse by Beddington (1992)10.1016/0968-0004(92)90321-Y
/ Trends Biol. Sci / NF-kB and related proteins: Rel/dorsal homologies meet ankyrin-like repeats by Blank (1992)10.1016/0092-8674(92)90632-M
/ Cell / Gastrulation in the mouse: The role of the homeobox gene goosecoid by Blum (1992)10.1101/gad.5.9.1538
/ Genes Dev / Regulated expression of C/EBP isoforms during adipocyte conversion of 3T3-L1 cells by Cao (1991)10.1242/dev.113.1.217
/ Development / Hepatocyte differentiation during endoderm-mesenchymal interactions prior to liver formation by Cascio (1991)10.1242/dev.116.3.783
/ Development / Expression patterns of vHNF-1 and HNF-1 homeoproteins in early postimplantation embryos suggest distinct and sequential developmental roles by Cereghini (1992)10.1073/pnas.90.9.3948
/ Proc. Natl. Acad. Sci.USA / Identification of nine novel tissue specific transcription factors of the HNF-3/forkhead DNA binding domain family by Clevidence (1993){'key': '2024121723182011500_DEVELOP_119_3_567C11', 'first-page': '81', 'article-title': 'The cell specific enhancer of the mouse transthyretin gene binds a common factor at one site and a liver-specific factor(s) at two other sites', 'volume': '8', 'author': 'Costa', 'year': '1988', 'journal-title': 'Mol. Cell Biol'}
/ Mol. Cell Biol / The cell specific enhancer of the mouse transthyretin gene binds a common factor at one site and a liver-specific factor(s) at two other sites by Costa (1988){'key': '2024121723182011500_DEVELOP_119_3_567C12', 'first-page': '1415', 'article-title': 'Multiple hepatic enriched nuclear factors function in the regulation of transthyretin and α1 antitrypsin genes', 'volume': '9', 'author': 'Costa', 'year': '1989', 'journal-title': 'Mol. Cell Biol'}
/ Mol. Cell Biol / Multiple hepatic enriched nuclear factors function in the regulation of transthyretin and α1 antitrypsin genes by Costa (1989)10.1016/0955-0674(91)90114-E
/ Curr. Opin. Cell Biol / Transcriptional regulation of liver specific gene expression by De Simone (1991)10.1101/gad.6.4.599
/ Genes Dev / A novel, activin inducible, blastopore lip-specific gene of Xenopus laevis contains a forkhead DNA binding domain by Dirksen (1992)10.1002/j.1460-2075.1989.tb03534.x
/ EMBO J / The structural and functional organisation of the murine HOX gene family resembles that of Drosophila homeotic genes by Duboule (1989){'key': '2024121723182011500_DEVELOP_119_3_567C16', 'first-page': '111', 'article-title': 'Hepatic induction in the avian embryo: specificity of reactive endoderm and inductive mesoderm', 'volume': '63', 'author': 'Fukuda-Taira', 'year': '1981', 'journal-title': 'J. Embryol. Exp. Morph'}
/ J. Embryol. Exp. Morph / Hepatic induction in the avian embryo: specificity of reactive endoderm and inductive mesoderm by Fukuda-Taira (1981)10.1016/0092-8674(89)90912-4
/ Cell / The murine and Drosophila homeo box gene complexes have common features of organisation and expression by Graham (1989)10.1101/gad.6.6.1030
/ Genes Dev / The Drosophila sloppy paired locus encodes two proteins involved in segmentation that show homology to mammalian transcription factors by Grossniklaus (1992)10.1073/pnas.89.18.8754
/ Proc. Natl. Acad. Sci.USA / Developmentally regulated Drosophila gene family encoding the forkhead domain by Häcker (1992)10.1038/353715a0
/ Nature / A structural taxonomy of DNA binding domains by Harrison (1991){'key': '2024121723182011500_DEVELOP_119_3_567C21', 'first-page': '139', 'article-title': 'A mutation that deletes the floor plate and disturbs axonal pathfinding in Zebrafish', 'volume': '16', 'author': 'Hatta', 'year': '1990', 'journal-title': 'Soc. Neurosci. Abstr'}
/ Soc. Neurosci. Abstr / A mutation that deletes the floor plate and disturbs axonal pathfinding in Zebrafish by Hatta (1990){'key': '2024121723182011500_DEVELOP_119_3_567C22', 'first-page': '289', 'article-title': 'Differential regulation of hepatocyte enriched transcription factors explains changes in albumin and transthyretin gene expression among hepatoma cells', 'volume': '3', 'author': 'Herbst', 'year': '1991', 'journal-title': 'The New Biologist'}
/ The New Biologist / Differential regulation of hepatocyte enriched transcription factors explains changes in albumin and transthyretin gene expression among hepatoma cells by Herbst (1991)10.1242/dev.113.3.913
/ Development / Expression pattern of the Brachyury gene in whole mount Twis/Twis mutant embryos by Herrmann (1991)10.1038/343617a0
/ Nature / Cloning of the T gene required in mesoderm formation in the mouse by Herrmann (1990)10.1016/0045-6039(80)90026-3
/ Cell Differentiation / Differentiation of the mouse hepatic primordium. 1. An analysis of tissue interactions in hepatic differentiation by Houssaint (1980){'key': '2024121723182011500_DEVELOP_119_3_567C26', 'first-page': '345', 'article-title': 'Terminal versus segmental development in the Drosophila embryo: the role of the homeotic gene fork head Roux’s Arch', 'volume': '197', 'author': 'Jürgens', 'year': '1988', 'journal-title': 'Dev. Biol'}
/ Dev. Biol / Terminal versus segmental development in the Drosophila embryo: the role of the homeotic gene fork head Roux’s Arch by Jürgens (1988)10.1073/pnas.90.16.7628
/ Proc. Natl. Acad. Sci.USA / Six novel members of the murine forkhead gene are developmentally regulated by Kaestner (1993)10.1126/science.1974085
/ Science / Murine developmental control genes by Kessel (1990)10.1016/0925-4773(92)90007-7
/ Mech. Dev / Activin A induced expression of a forkhead related gene in posterior chordamesoderm of Xenopus laevis by Knöchel (1992)10.1242/dev.109.2.473
/ Development / Fetal and adult localisation of C/EBP : evidence for combinatorial action of transcription factors in cell-specific gene expression by Kuo (1990)10.1038/355457a0
/ Nature / A transcriptional hierarchy involved in mammalian cell-type specification by Kuo (1992)10.1101/gad.4.8.1427
/ Genes Dev / HNF-3A, a hepatic enriched transcription factor of novel structure is regulated transcriptionally by Lai (1990)10.1101/gad.5.3.416
/ Genes Dev / Hepatocyte nuclear factor 3α belongs to a family in mammals that is homologous to the Drosophila homeotic gene forkhead by Lai (1991)10.1007/BF00310060
/ Anat Embryol / The lining of the gut in the developing rat embryo. Its relation to the hypoblast (primary endoderm) and the notochord by Lamers (1987)10.1101/gad.2.7.786
/ Genes Dev / Isolation of a recombinant copy of the gene encoding C/EBP by Landschulz (1988)10.1016/0012-1606(86)90253-8
/ Dev. Biol / Cell fate and cell lineage in the endoderm of the presomite mouse embryo, studied with an intracellular tracer by Lawson (1986)10.1242/dev.101.3.627
/ Development / Cell fate, morphogenetic movement and population kinetics of embryonic endoderm at the time of germ layer formation in the mouse by Lawson (1987)10.1242/dev.113.3.891
/ Development / Clonal analsyis of epiblast fate during germ layer formation in the mouse embryo by Lawson (1991){'key': '2024121723182011500_DEVELOP_119_3_567C39', 'first-page': '3', 'article-title': 'Clonal analysis of cell fate during gastrulation and early neurulation in the mouse', 'volume-title': 'In Postimplantation Development in the Mouse. Ciba Found Symp', 'author': 'Lawson', 'year': '1992'}
/ In Postimplantation Development in the Mouse. Ciba Found Symp / Clonal analysis of cell fate during gastrulation and early neurulation in the mouse by Lawson (1992)10.1016/0012-1606(68)90092-4
/ Dev. Biol / Synthese du glycogene dans les hepatocytes en voie de differentiation: role des mesenchymes homologue et heterologues by LeDouarin (1968){'key': '2024121723182011500_DEVELOP_119_3_567C41', 'first-page': '427', 'article-title': 'An experimental analysis of liver development', 'volume': '53', 'author': 'LeDouarin', 'year': '1975', 'journal-title': 'Med. Biol'}
/ Med. Biol / An experimental analysis of liver development by LeDouarin (1975)10.1007/BF02136960
/ Experientia / Differentiation of endodermal tissues in homographs of primitive ectoderm from two layered rat embryonic shields by Levak-Svajger (1971)10.1073/pnas.88.17.7739
/ Proc. Natl. Acad. Sci. USA / Cloning of a cellular factor, interleukin binding factor, that binds to NFAT like motifs in the human immunodeficiency virus long terminal repeat by Li (1991)10.1016/0888-7543(92)90138-I
/ Genomics / The complete DNA sequence of yeast chromosome III by Li (1992)10.1016/0092-8674(92)90471-N
/ Cell / Homeobox genes and axial patterning by McGinnis (1992)10.1016/0092-8674(90)90808-R
/ Cell / DBP, a liver enriched transcription activator, is expressed late in ontogeny and its tissue specificity is determined posttranscriptionally by Mueller (1990)10.1038/357038a0
/ Nature / The complete DNA sequence of yeast chromosome III by Oliver (1992)10.1016/0925-4773(91)90071-D
/ Mech. Dev / vHNF-1 is expressed in epithelial cells of distinct embryonic origin during development and precedes HNF-1 expression by Ott (1991)10.1146/annurev.bi.61.070192.005201
/ Annu. Rev. Biochem / Transcription factors: Structural families and principles of DNA recognition by Pabo (1992){'key': '2024121723182011500_DEVELOP_119_3_567C50', 'first-page': '9', 'article-title': 'Hepatic nuclear factor 3β contains two transcriptional activation domains, one of which is novel and conserved with the Drosophila forkhead protein', 'volume': '12', 'author': 'Pani', 'year': '1992', 'journal-title': 'Mol. Cell Biol'}
/ Mol. Cell Biol / Hepatic nuclear factor 3β contains two transcriptional activation domains, one of which is novel and conserved with the Drosophila forkhead protein by Pani (1992)10.1242/dev.113.Supplement_2.105
/ Development / Control of dorsoventral pattern in vertebrate neural development: induction and polarising properties of the floor plate by Placzek (1991)10.1007/BF00318092
/ Anat Embryol / The head process and the formation of the definitive endoderm in the mouse embryo by Poelmann (1981)10.1101/gad.6.12a.2299
/ Genes Dev / Drosophila C/EBP: a tissue specific DNA-binding protein required for embryonic development by Rorth (1992)10.1242/dev.116.1.81
/ Development / Pintallavis, a gene expressed in the organiser and midline cells of frog embryos: involvement in the development of the neural axis by Ruiz i Altaba (1992)10.1242/dev.118.1.47
/ Development / Differential expression of multiple forkhead related genes during gastrulation and axial pattern formation in the mouse embryo by Sasaki (1993)10.1101/gad.4.12b.2353
/ Genes Dev / Liver enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily by Sladek (1990){'key': '2024121723182011500_DEVELOP_119_3_567C57', 'first-page': '205', 'article-title': 'Early Embryology', 'volume-title': 'In Biology of the Laboratory Mouse', 'author': 'Snell', 'year': '1966'}
/ In Biology of the Laboratory Mouse / Early Embryology by Snell (1966)10.1038/343273a0
/ Nature / Origin of cells giving rise to mesoderm and endoderm in chick embryo by Stern (1990)10.1101/gad.7.7b.1436
/ Genes Dev / Axial, a target gene of mesoderm and neural induction, shows altered expression in cyclops mutant zebrafish embryos by Strähle (1993)10.1242/dev.99.1.109
/ Development / The formation of mesodermal tissues in the mouse embryo during gastrulation and early organogenesis by Tam (1987)10.1242/dev.107.1.55
/ Development / Regionalisation of the mouse embryonic ectoderm: allocation of prospective ectodermal tissues during gastrulation by Tam (1989){'key': '2024121723182011500_DEVELOP_119_3_567C62', 'first-page': '27', 'article-title': 'Establishment and organisation of germ layers in the gastrulating mouse embryo', 'volume-title': 'In Postimplantation Development in the Mouse. Ciba Found Symp', 'author': 'Tam', 'year': '1992'}
/ In Postimplantation Development in the Mouse. Ciba Found Symp / Establishment and organisation of germ layers in the gastrulating mouse embryo by Tam (1992)10.1016/0896-6273(92)90210-5
/ Neuron / Telencephalon restricted expression of BF-1, a new member of the HNF-3/forkhead gene family, in the developing rat brain by Tao (1992)10.1101/gad.5.12a.2225
/ Genes Dev / Tissue specific expression of the gene encoding HNF-1 may involve HNF-4 by Tian (1991){'key': '2024121723182011500_DEVELOP_119_3_567C65', 'first-page': '91', 'article-title': 'Induction of an additional floor plate in the neural tube', 'volume': '23', 'author': 'van Straaten', 'year': '1985', 'journal-title': 'Acta. Morphol. Neerl. Scand'}
/ Acta. Morphol. Neerl. Scand / Induction of an additional floor plate in the neural tube by van Straaten (1985)10.1007/BF01744261
/ Anat. Embryol / Development of floor plate, neuronal and axonal outgrowth pattern in the early spinal cord of the notochord deficient chick embryo by van Straaten (1991)10.1016/0092-8674(89)90133-5
/ Cell / The homeotic gene forkhead encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo by Weigel (1989)10.1016/0092-8674(90)90439-L
/ Cell / The forkhead domain: a novel DNA binding motif of eukaryotic transcription factors? by Weigel (1990)10.1016/0092-8674(87)90664-7
/ Cell / Expression of the proto oncogene int 1 is restricted to specific neural cells in the developing mouse embryo by Wilkinson (1987)10.1038/343657a0
/ Nature / Expression pattern of the mouse T gene and its role in mesoderm formation by Wilkinson (1990)10.1073/pnas.88.9.3807
/ Proc. Natl. Acad. Sci.USA / The different tissue transcription patterns of genes for HNF-1, C/EBP, HNF-3 and HNF-4, protein factors that govern liver-specific transcription by Xanthopoulos (1991)10.1016/0092-8674(91)90247-V
/ Cell / Control of cell pattern in the developing nervous system: Polarising activity of the floor plate and notochord by Yamada (1991)10.1002/j.1460-2075.1993.tb05685.x
/ EMBO J / The expression pattern of a Drosophila homolog to the mouse transcription factor HNF-4 suggests a determinative role in gut formation by Zhong (1993)10.1038/361543a0
/ Nature / Nodal is a novel TGF–β like gene expressed in the mouse node during gastrulation by Zhou (1993)
Dates
Type | When |
---|---|
Created | 4 years, 4 months ago (April 25, 2021, 9:24 p.m.) |
Deposited | 8 months, 1 week ago (Dec. 17, 2024, 6:18 p.m.) |
Indexed | 5 days, 16 hours ago (Aug. 23, 2025, 1:22 a.m.) |
Issued | 31 years, 9 months ago (Nov. 1, 1993) |
Published | 31 years, 9 months ago (Nov. 1, 1993) |
Published Online | 31 years, 9 months ago (Nov. 1, 1993) |
Published Print | 31 years, 9 months ago (Nov. 1, 1993) |
@article{Monaghan_1993, title={Postimplantation expression patterns indicate a role for the mouse forkhead/HNF-3 α, β and γ genes in determination of the definitive endoderm, chordamesoderm and neuroectoderm}, volume={119}, ISSN={1477-9129}, url={http://dx.doi.org/10.1242/dev.119.3.567}, DOI={10.1242/dev.119.3.567}, number={3}, journal={Development}, publisher={The Company of Biologists}, author={Monaghan, A. Paula and Kaestner, Klaus H. and Grau, Evelyn and Schütz, Günther}, year={1993}, month=nov, pages={567–578} }