Advertisement
JOURNAL ARTICLES
The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins
S.L. Ang, A. Wierda, D. Wong, K.A. Stevens, S. Cascio, J. Rossant, K.S. Zaret
Development 1993 119: 1301-1315;

Summary

Little is known about genes that govern the development of the definitive endoderm in mammals; this germ layer gives rise to the intestinal epithelium and various other cell types, such as hepatocytes, derived from the gut. The discovery that the rat hepatocyte transcription factor HNF3 is similar to the Drosophila forkhead gene, which plays a critical role in gut development in the fly, led us to isolate genes containing the HNF3/forkhead (HFH) domain that are expressed in mouse endoderm development. We recovered mouse HNF3 beta from an embryo cDNA library and found that the gene is first expressed in the anterior portion of the primitive streak at the onset of gastrulation, in a region where definitive endoderm first arises. Its expression persists in axial structures derived from the mouse equivalent of Hensen's node, namely definitive endoderm and notochord, and in the ventral region of the developing neural tube. Expression of the highly related gene, HNF3 alpha, appears to initiate later than HNF3 beta and is first seen in midline endoderm cells. Expression subsequently appears in notochord, ventral neural tube, and gut endoderm in patterns similar to HNF3 beta. Microscale DNA binding assays show that HNF3 proteins are detectable in the midgut at 9.5 days p.c. At later stages HNF3 mRNAs and protein are expressed strongly in endoderm-derived tissues such as the liver. HNF3 is also the only known hepatocyte-enriched transcription factor present in a highly de-differentiated liver cell line that retains the capacity to redifferentiate to the hepatic phenotype. Taken together, these studies suggest that HNF3 alpha and HNF3 beta are involved in both the initiation and maintenance of the endodermal lineage. We also discovered a novel HFH-containing gene, HFH-E5.1, that is expressed transiently in posterior ectoderm and mesoderm at the primitive streak stage, and later predominantly in the neural tube. HFH-E5.1 is highly similar in structure and expression profile to the Drosophila HFH gene FD4, suggesting that HFH family members have different, evolutionarily conserved roles in development.

REFERENCES

    1. Ang S.-L.,
    2. Rossant J.
    (1993). Anterior mesendoderm induces mouse Engrailed genes in explant cultures. Development 118, 139–149
    OpenUrlAbstract
    1. Baumheuter S.,
    2. Courtois G.,
    3. Crabtree G. R.
    (1988). A variant nuclear protein in dedifferentiated hepatoma cells binds to the same functional sequences in thefibrinogen gene promoter as HNF-1. EMBO J 7, 2485–2493
    OpenUrlPubMedWeb of Science
    1. Birkenmeier E. H.,
    2. Gwynn B.,
    3. Howard S.,
    4. Jerry J.,
    5. Gordon J. I.,
    6. Landschulz W. H.,
    7. McKnight S. L.
    (1989). Tissue-specific expression, developmental regulation, and genetic mapping of the gene encoding CCAAT/enhancer binding protein. Genes Dev 3, 1146–1156
    OpenUrlAbstract/FREE Full Text
    1. Blum M.,
    2. Gaunt S. J.,
    3. Cho K. W. Y.,
    4. Steinbeisser H.,
    5. Blumberg B.,
    6. Bittner D.,
    7. De Robertis E. M.
    (1992). Gastrulation in the mouse: The role of the homeobox gene goosecoid. Cell 69, 1097–1106
    OpenUrlCrossRefPubMedWeb of Science
    1. Blumenfeld M.,
    2. Maury M.,
    3. Chouard T.,
    4. Yaniv M.,
    5. Condamine H.
    (1991). Hepatic nuclear factor 1 (HNF1) shows a wider distribution than products of its known target genes in developing mouse. Development 113, 589–599
    OpenUrlAbstract
    1. Cascio S.,
    2. Zaret K. S.
    (1991). Hepatocyte differentiation initiates during endodermal-mesenchymal interactions prior to liver formation. Development 113, 217–225
    OpenUrlAbstract
    1. Cereghini S.,
    2. Blumenfeld M.,
    3. Yaniv M.
    (1988). A liver-specific factor essential for albumin transcription differs between differentiated and dedifferentiated rate hepatoma cells. Genes Dev 2, 957–974
    OpenUrlAbstract/FREE Full Text
    1. Cereghini S.,
    2. Ott M.-O.,
    3. Power S.,
    4. Maury M.
    (1992). Expression patterns of vHNF1 and HNF1 homeoproteins in early postimplantation embryos suggest distinct and sequential developmental roles. Development 116, 783–797
    OpenUrlAbstract
    1. Chodosh L. A.,
    2. Carthew R. W.,
    3. Sharp P. A.
    (1987). A single polypeptide possesses the binding and transcription activities of the major late transcription factor of adenovirus. Mol. Cell. Biol 6, 4723–4733
    OpenUrl
    1. Clevidence D. E.,
    2. Overdier D. G.,
    3. Tao W.,
    4. Qian X.,
    5. Pani L.,
    6. Lai E.,
    7. Costa R. H.
    (1993). Identification of nine novel tissue-specific transcription factors of the HNF-3/forkhead DNA binding domain family. Proc. Natl. Acad. Sci. USA 90, 3948–3952
    OpenUrlAbstract/FREE Full Text
    1. Conlon R. A.,
    2. Rossant J.
    (1992). Exogenous retinoic acid rapidly induces anterior ectopic expression of murine Hox-2 genes in vivo. Development 116, 357–358
    OpenUrlAbstract/FREE Full Text
    1. Costa R. H.,
    2. Grayson D. R.,
    3. Darnell J. E. Jr..
    (1989). Multiple hepatocyte-enriched nuclear factors function in the regulation of transthyretin and a1-antitrypsin genes. Mol. Cell Biol 9, 1415–1425
    OpenUrlAbstract/FREE Full Text
    1. Costa R. H.,
    2. Van Dyke T. A.,
    3. Yan C.,
    4. Kuo R.,
    5. Darnell J. E. Jr..
    (1990). Similarities in transthyretin gene expression and differences in transcription factors: Liver and yolk sac compared to choroid plexus. Proc. Natl. Acad. Sci. USA 87, 6589–6593
    OpenUrlAbstract/FREE Full Text
    1. Courtois G.,
    2. Morgan J. G.,
    3. Campbell L. A.,
    4. Fourel G.,
    5. Crabtree G. R.
    (1987). Interaction of a liver-specific nuclear factor with the fibrinogen and a1 -antitrypsin promoters. Science 238, 688–692
    OpenUrlAbstract/FREE Full Text
    1. DeSimone V.,
    2. DeMagistris L.,
    3. Lazzaro D.,
    4. Gerstner J.,
    5. Monaci P.,
    6. Nicosia A.,
    7. Cortese R.
    (1991). LFB3, a heterodimer-forming homeoprotein of the LFB1 family, is expressed in specialized epithelia. EMBO J 10, 1435–1443
    OpenUrlPubMedWeb of Science
    1. DiPersio C. M.,
    2. Jackson D. A.,
    3. Zaret K. S.
    (1991). The extracellular matrix coordinately modulates liver transcription factors and hepatocyte morphology. Mol. Cell Biol 11, 4405–4414
    OpenUrlAbstract/FREE Full Text
    1. Dirksen M. L.,
    2. Jamrich M.
    (1992). A novel, activin-inducible, blastopore lip-specific gene of Xenopus laevis contains a fork head DNA-binding domain. Genes Dev 6, 599–608
    OpenUrlAbstract/FREE Full Text
    1. Fahrner K.,
    2. Hogan B. L. M.,
    3. Flavell R. A.
    (1987). Transcription of H-2 and Qa genes in embryonic and adult mice. EMBO J 6, 1265–1271
    OpenUrlPubMed
    1. Gardner R. L.,
    2. Rossant J.
    (1979). Investigation of the fate of 4. 5 daypost-coitum mouse inner cell mass cells by blastocyst injection. J. Embryol. Exp. Morph 52, 141–152
    OpenUrlPubMedWeb of Science
    1. Grossinklaus U.,
    2. Pearson R. K.,
    3. Gehring W. J.
    (1992). The Drosophila sloppy paired locus encodes two proteins involved in segmentation that show homology to mammalian transcription factors. Genes Dev 6, 1030–1051
    OpenUrlAbstract/FREE Full Text
    1. Häcker U.,
    2. Grossinklaus U.,
    3. Gehring W. J.,
    4. Jackle H.
    (1992). Developmentally regulated Drosophila gene family encoding the forkhead domain. Proc. Natl. Acad. Sci. USA 89, 8754–8758
    OpenUrlAbstract/FREE Full Text
    1. Houssaint E.
    (1980). Differentiation of the mouse hepatic primordium. I. An analysis of tissue interactions in hepatocyte differentiation. Cell Differentiation 9, 269–279
    OpenUrlCrossRefPubMedWeb of Science
    1. Jackson D. A.,
    2. Rowader K. E.,
    3. Stevens K.,
    4. Jiang C.,
    5. Milos P.,
    6. Zaret K. S.
    (1993). Modulation of liver-specific transcription by interactions between hepatocyte nuclear factor 3 and nuclear factor 1 binding DNA in close apposition. Mol. Cell. Biol 13, 2401–2410
    OpenUrlAbstract/FREE Full Text
    1. Knöchel S.,
    2. Lef J.,
    3. Clement J.,
    4. Klocke B.,
    5. Fill S.,
    6. Köster M.,
    7. Knöchel W.
    (1992). Activin A induced expression of fork head related genes in posterior chordamesoderm (notochord) of Xenopuslaevis. Mech. Dev 38, 157–165
    OpenUrlCrossRefPubMedWeb of Science
    1. Kozak M.
    (1986). Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell 44, 283–292
    OpenUrlCrossRefPubMedWeb of Science
    1. Kuo C. F.,
    2. Xanthopoulos K. G.,
    3. Darnell J. E. Jr..
    (1990). Fetal and adult localization of C/EBP: evidence for combinatorial action of transcription factors in cell-specific gene expression. Development 109, 473–481
    OpenUrlAbstract
    1. Kuo C. J.,
    2. Conley P. B.,
    3. Chen L.,
    4. Sladek F. M.,
    5. Darnell J. E. Jr..,
    6. Crabtree G. R.
    (1992). A transcriptional hierarchy involved in mammalian cell-type specification. Nature 355, 457–461
    OpenUrlCrossRefPubMedWeb of Science
    1. Laemmli U. K.
    (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680–685
    OpenUrlCrossRefPubMedWeb of Science
    1. Lai E.,
    2. Prezioso V. R.,
    3. Smith E.,
    4. Litvin O.,
    5. Costa R. H.,
    6. Darnell J. E. Jr..
    (1990). HNF-3A, a hepatocyte-enriched transcription factor of novel structure is regulated transcriptionally. Genes Dev 4, 1427–1436
    OpenUrlAbstract/FREE Full Text
    1. Lai E.,
    2. Prezioso V. R.,
    3. Tao W.,
    4. Chen W. S.,
    5. Darnell J. E. Jr..
    (1991). Hepatocyte nuclear factor 3belongs to a gene family in mammals that is homologous to the Drosophila homeotic gene fork head. Genes Dev 5, 416–427
    OpenUrlAbstract/FREE Full Text
    1. Lawson K. A.,
    2. Meneses J. J.,
    3. Pedersen R. A.
    (1991). Clonal analysis of epiblast fate during germ layer formation in the mouse embryo. Development 113, 891–911
    OpenUrlAbstract
    1. Lawson K. A.,
    2. Pedersen R. A.
    (1987). Cell fate, morphogenetic movement and population kinetics of embryonic endoderm at the time of germ layer formation in the mouse. Development 101, 627–652
    OpenUrlAbstract
    1. Le Douarin N. M.
    (1975). An experimental analysis of liver development. Medical Biology 53, 427–455
    OpenUrlPubMedWeb of Science
    1. Li C.,
    2. Lusis A. J.,
    3. Sparkes R.,
    4. Tran S.-M.,
    5. Gaynor R.
    (1992). Characterization and chromosomal mapping of the gene encoding the cellular DNA binding protein HTLF. Genomics 13, 659–664
    OpenUrlCrossRef
    1. Liu J.-K.,
    2. DiPersio C. M.,
    3. Zaret K. S.
    (1991). Extracellular signals that regulate liver transcription factors during hepatic differentiation in vitro. Mol. Cell Biol 11, 773–784
    OpenUrlAbstract/FREE Full Text
    1. Miller L. M.,
    2. Gallegos M. E.,
    3. Morisseau B. A.,
    4. Kim S. K.
    (1993). lin-31, a Caenorhabditis elegans HNF-3/ fork head transcription factor homolog, specifies three alternative cell fates in vulval development. Genes Dev 7, 933–947
    OpenUrlAbstract/FREE Full Text
    1. Morle F.,
    2. Lopez B.,
    3. Henni T.,
    4. Godet J.
    (1985). -Thallasaemia associated with the deletion of two nucleotides at position 2 and3 preceding the AUG codon. EMBO J 4, 1245–1250
    OpenUrlPubMedWeb of Science
    1. Mueller C. R.,
    2. Maire P.,
    3. Schibler U.
    (1990). DBP, a liver-enriched transcriptional activator, is expressed late in ontogeny and its tissue specificity is determined posttranscriptionally. Cell 61, 279–291
    OpenUrlCrossRefPubMedWeb of Science
    1. Nitch D.,
    2. Boshart M.,
    3. Schutz G.
    (1993). Extinction of tyrosine aminotransferase gene activity in somatic cell hybrids involves modification and loss of several essential transcriptional activators. Genes Dev 7, 308–319
    OpenUrlAbstract/FREE Full Text
    1. Pani L.,
    2. Qian X.,
    3. Clevidence D.,
    4. Costa R. H.
    (1992). The restrictedS.-L. Ang and others1315HNF3 proteins and endoderm developmentpromoter activity of the liver transcription factor hepatocyte nuclear factor 3b involves a cell-specific factor and positive autoactivation. Mol. Cell Biol 12, 552–562
    OpenUrlAbstract/FREE Full Text
    1. Paul J.,
    2. Conkie D.,
    3. Freshney R. I.
    (1969). Erythropoietic cell population changes during the hepatic phase of erythropoiesis in the fetal mouse. Cell Tissue Kinet 2, 283–294
    OpenUrlWeb of Science
    1. Poelmann R. E.
    (1981). The head-process and the formation of the definitive endoderm in the mouse embryo. Anat. Rec 162, 41–49
    OpenUrlCrossRef
    1. Raymondjean M.,
    2. Cereghini S.,
    3. Yaniv M.
    (1988). Several distinct ‘CCAAT’ box binding proteins coexist in eukaryotic cells. Proc. Natl. Acad. Sci. USA 85, 757–761
    OpenUrlAbstract/FREE Full Text
    1. Reaume A. G.,
    2. Conlon R. A.,
    3. Zirngibl R.,
    4. Yamaguchi T. P.,
    5. Rossant J.
    (1992). Expression analysis of a Notch homologue in the mouse embryo. Dev. Biol 154, 377–387
    OpenUrlCrossRefPubMedWeb of Science
    1. Rosenquist G. C.
    (1971). The location of the pregut endoderm in the chick embryo at the primitive streak stage as determined by radioautographic mapping. Dev. Biol 26, 323–335
    OpenUrlCrossRefPubMedWeb of Science
    1. Rosenquist G. C.
    (1972). Endoderm movements in the chick embryo between the early short streak and head process stages. J. Exp. Zool 180, 95–104
    OpenUrlCrossRefPubMed
    1. Ruiz i Altaba A.,
    2. Jessell T. M.
    (1992). Pintallavis, a gene expressed in the organizer and midline cells of frog embryos: involvement in the development of the neural axis. Development 116, 81–93
    OpenUrlAbstract
    1. Sanders E. E.,
    2. Bellairs R.,
    3. Portch P. A.
    (1978). In vivo and in vitro studies on the hypoblast and definitive endoblast of avian embryos. J. Embryol. Exp. Morph 46, 187–205
    OpenUrlPubMed
    1. Santoro C.,
    2. Mermod N.,
    3. Andrews P. C.,
    4. Tjian R.
    (1988). A family of human CCAAT-box-binding proteins active in transcription and DNA replication: cloning and expression of multiple cDNAs. Nature 334, 218–223
    OpenUrlCrossRefPubMed
    1. Sasaki H.,
    2. Hogan B. L. M.
    (1993). Differential expression of multiple fork head related genes during gastrulation and pattern formation in the mouse embryo. Development 118, 47–59
    OpenUrlAbstract
    1. Schoenwolf G. C.,
    2. Garcia-Martinez V.,
    3. Dias M. S.
    (1992). Mesoderm movement and fate during avian gastrulation and neurulation. Dev. Dynam 193, 235–248
    OpenUrlCrossRefPubMedWeb of Science
    1. Schreiber E.,
    2. Matthias P.,
    3. Muller M. M.,
    4. Schaffner W.
    (1989). Rapid detection of octamer binding proteins with ‘mini-extracts’, prepared from a small number of cells. Nuc. Acids Res 17, 6419–.
    OpenUrlFREE Full Text
    1. Selleck M. A. J.,
    2. Stern C. D.
    (1991). Fate mapping and cell lineage analysis of Hensen's node in the chick embryo. Development 112, 615–626
    OpenUrlAbstract
    1. Sladek F. M.,
    2. Zhong W.,
    3. Lai E.,
    4. Darnell J. E. Jr..
    (1990). Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily. Genes Dev 4, 2353–2364
    OpenUrlAbstract/FREE Full Text
    1. Strähle U.,
    2. Blader P.,
    3. Henrique D.,
    4. Ingham P. W.
    (1993). Axial, a zebrafish gene expressed along the developing body axis, shows altered expression in cyclops mutant embryos. Genes Dev 7, 1436–1446
    OpenUrlAbstract/FREE Full Text
    1. Taira M.,
    2. Jamrich M.,
    3. Good P. J.,
    4. David I. B.
    (1992). The LIM domain-containing homeobox gene Xlim −1 is expressed specifically in the organizer region of Xenopus gastrula embryos. Genes Dev 6, 356–366
    OpenUrlAbstract/FREE Full Text
    1. Tao W.,
    2. Lai E.
    (1992). Telencephalon-restricted expression of BF-1, a new member of the HNF-3/ fork head gene family, in the developing rat brain. Neuron 8, 957–966
    OpenUrlCrossRefPubMedWeb of Science
    1. von Dassow G.,
    2. Schmidt J. E.,
    3. Kimehanan D.
    (1993). Induction of the Xenopus organizer: expression and regulation of Xnot, a novel FGF and activity-regulator homeobox gene. Genes Dev 7, 355–367
    OpenUrlAbstract/FREE Full Text
    1. Weigel D.,
    2. Jäckle H.
    (1990). The fork head domain: a novel DNA binding motif of eukaryotic transcription factors. Cell 63, 455–456
    OpenUrlCrossRefPubMedWeb of Science
    1. Weigel D.,
    2. Jurgens G.,
    3. Kuttner F.,
    4. Seifert E.,
    5. Jäckle H.
    (1989). The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo. Cell 57, 645–658
    OpenUrlCrossRefPubMedWeb of Science
    1. Yamaguchi T. P.,
    2. Conlon R. A.,
    3. Rossant J.
    (1992). Expression of the fibroblast growth factor receptor FGFR-1/flg during gastrulation and segmentation in the mouse embryo. Dev. Biol 152, 75–88
    OpenUrlCrossRefPubMedWeb of Science
    1. Zaret K. S.,
    2. DiPersio C. M.,
    3. Jackson D. A.,
    4. Montigny W. J.,
    5. Weinstat D. L.
    (1988). Conditional enhancement of liver-specific gene transcription. Proc. Natl. Acad. Sci. USA 85, 9076–9080
    OpenUrlAbstract/FREE Full Text
Back to top

 Download PDF

Email
JOURNAL ARTICLES
The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins
S.L. Ang, A. Wierda, D. Wong, K.A. Stevens, S. Cascio, J. Rossant, K.S. Zaret
Development 1993 119: 1301-1315;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Alerts

Article navigation

Other journals from The Company of Biologists

Advertisement

Kathryn Virginia Anderson (1952-2020)

Developmental geneticist Kathryn Anderson passed away at home on 30 November 2020. Tamara Caspary, a former postdoc and friend, remembers Kathryn and her remarkable contribution to developmental biology.

Zooming into 2021

In a new Editorial, Editor-in-Chief James Briscoe and Executive Editor Katherine Brown reflect on the triumphs and tribulations of the last 12 months, and look towards a hopefully calmer and more predictable year.

Read & Publish participation extends worldwide

Over 60 institutions in 12 countries are now participating in our Read & Publish initiative. Here, James Briscoe explains what this means for his institution, The Francis Crick Institute. Find out more and view our full list of participating institutions.

Upcoming special issues

Imaging Development, Stem Cells and Regeneration
Submission deadline: 30 March 2021
Publication: mid-2021

The Immune System in Development and Regeneration
Guest editors: Florent Ginhoux and Paul Martin
Submission deadline: 1 September 2021
Publication: Spring 2022

Both special issues welcome Review articles as well as Research articles, and will be widely promoted online and at key global conferences.

Development presents...

Our successful webinar series continues into 2021, with early-career researchers presenting their papers and a chance to virtually network with the developmental biology community afterwards. Sign up to join our next session:

10 February
Time: 13:00 (GMT)
Chaired by: preLights