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JOURNAL ARTICLES
The bHLH-Zip transcription factor Tfeb is essential for placental vascularization
E. Steingrimsson, L. Tessarollo, S.W. Reid, N.A. Jenkins, N.G. Copeland
Development 1998 125: 4607-4616;
E. Steingrimsson
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L. Tessarollo
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S.W. Reid
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N.A. Jenkins
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N.G. Copeland
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Summary

Tfeb is a member of the basic Helix-Loop-Helix-Zipper family of transcription factors. In vitro studies have shown that TFEB can bind DNA as a homodimer or as a heterodimer with three closely related family members: MITF, TFE3 and TFEC. While mutations of Mitf have been shown to affect the development of a number of cell types including melanocytes, osteoclasts, and masts cells, little is known about the phenotypic consequences of mutations at Tfe3, Tfeb and Tfec. Here we show that mice with a targeted disruption of Tfeb die between 9.5 and 10.5 days in embryonic development and have severe defects in placental vascularization. Tfeb is expressed at low levels in the embryo but at high levels in the labyrinthine trophoblast cells of the placenta. While labyrinthine cells are present in the mutant Tfeb placenta, they fail to express VEGF, a potent mitogen required for normal vasculogenesis of the embryo and extraembryonic tissues. In Tfeb mutant embryos the embryonic vasculature forms normally but few vessels are seen entering the placenta and those that do enter fail to thrive and branch normally. Our results indicate that Tfeb plays a critical role in the signal transduction processes required for normal vascularization of the placenta.

REFERENCES

    1. Amati B.,
    2. Land H.
    (1994) Myc-Max-Mad: a transcription factor network controlling cell cycle progression, differentiation and death. Curr. Opin. Genet. Dev 4, 102–108
    OpenUrlCrossRefPubMed
    1. Atchley W. R.,
    2. Fitch W. M.
    (1997) A natural classification of the basic helix-loop-helix class of transcription factors. Proc. Natl. Acad. Sci. USA 94, 5172–5176
    OpenUrlAbstract/FREE Full Text
    1. Ayer D. E.,
    2. Kretzner L.,
    3. Eisenman R. N.
    (1993) Mad: A heterodimeric partner for Max that antagonizes Myc transcriptional activity. Cell 72, 211–222
    OpenUrlCrossRefPubMedWeb of Science
    1. Ayer D. E.,
    2. Lawrence Q. A.,
    3. Eisenmann R. N.
    (1995) Mad-Maxtranscriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3. Cell 80, 767–776
    OpenUrlCrossRefPubMedWeb of Science
    1. Beckmann H.,
    2. Su L.-K.,
    3. Kadesch T.
    (1990) TFE3: A helix-loop-helix protein that activates transcription through the immunoglobulin enhancerE3 motif. Genes Dev 4, 167–179
    OpenUrlAbstract/FREE Full Text
    1. Carmeliet P.,
    2. Ferreira V.,
    3. Breier G.,
    4. Pollefeyt S.,
    5. Kieckens L.,
    6. Gertsenstein M.,
    7. Fahrig M.,
    8. Vandenhoeck A.,
    9. Harpal K.,
    10. Eberhardt C.,
    11. Declercq C.,
    12. Pawling J.,
    13. Moons L.,
    14. Collen D.,
    15. Risau W.,
    16. Nagy A.
    (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380, 435–439
    OpenUrlCrossRefPubMedWeb of Science
    1. Carr C. S.,
    2. Sharp P. A.
    (1990) A helix-loop-helix protein related to the immunoglobulin E box-binding proteins. Mol. Cell. Biol 10, 4384–4388
    OpenUrlAbstract/FREE Full Text
    1. De Vries C.,
    2. Escobedo J. A.,
    3. Ueno H.,
    4. Houck K.,
    5. Ferrara N.,
    6. Williams L. T.
    (1992) The fms -like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 255, 989–991
    OpenUrlAbstract/FREE Full Text
    1. Dumont D. J.,
    2. Fong G.-H.,
    3. Puri M. C.,
    4. Gradwohl G.,
    5. Alitalo K.,
    6. Breitman M. L.
    (1995) Vascularization of the mouse embryo: A study of flk1, tek, tie, and vascular endothelial growth factor expression during development. Dev. Dyn 203, 80–92
    OpenUrlCrossRefPubMedWeb of Science
    1. Ferrara N.,
    2. Carver-Moore K.,
    3. Chen H.,
    4. Dowd M.,
    5. Lu L.,
    6. O'Shea K. S.,
    7. Powell-Braxton L.,
    8. Hillan K. J.,
    9. Moore M. W.
    (1996) Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380, 439–442
    OpenUrlCrossRefPubMedWeb of Science
    1. Forsythe J. A.,
    2. Jiang B.-H.,
    3. Iyer N. V.,
    4. Agani F.,
    5. Leung S. W.,
    6. Koos R. D.,
    7. Semenza G. L.
    (1996) Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol. Cell. Biol 16, 4604–4613
    OpenUrlAbstract/FREE Full Text
    1. Guillemot F.,
    2. Nagy A.,
    3. Auerbach A.,
    4. Rossant J.,
    5. Joyner A. L.
    (1994) Essential role of Mash-2 in extraembryonic development. Nature 371, 333–336
    OpenUrlCrossRefPubMed
    1. Hemesath T. J.,
    2. Steingrímsson E.,
    3. McGill G.,
    4. Hansen M. J.,
    5. Vaught J.,
    6. Hodgkinson C. A.,
    7. Arnheiter H.,
    8. Copeland N. G.,
    9. Jenkins N. A.,
    10. Fisher D. E.
    (1994) microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family. Genes Dev 8, 2770–80
    OpenUrlAbstract/FREE Full Text
    1. Hodgkinson C. A.,
    2. Moore K. J.,
    3. Nakayama A.,
    4. Steingrímsson E.,
    5. Copeland N. G.,
    6. Jenkins N. A.,
    7. Arnheiter H.
    (1993) Mutations at the mouse microphthalmia locus are associated with defects in a gene encoding a novel basic-helix-loop-helix-zipper protein. Cell 74, 395–404
    OpenUrlCrossRefPubMedWeb of Science
    1. Hughes M. J.,
    2. Lingrel J. B.,
    3. Krakowsky J. M.,
    4. Anderson K. P.
    (1993) A helix-loop-helix transcription factor-like gene is located at the mi locus. J. Biol. Chem 268, 20687–20690
    OpenUrlAbstract/FREE Full Text
    1. Hurlin P. J.,
    2. Queva C.,
    3. Eisenman R. N.
    (1997) Mnt, a novel Max-interacting protein is coexpressed with Myc in proliferating cells and mediates repression at Myc binding sites. Genes Dev 11, 44–58
    OpenUrlAbstract/FREE Full Text
    1. Hurlin P. J.,
    2. Queva C.,
    3. Koskinen P. J.,
    4. Steingrímsson E.,
    5. Ayer D. E.,
    6. Copeland N. G.,
    7. Jenkins N. A.,
    8. Eisenman R. N.
    (1995) Mad3 and Mad4: Novel max-interacting transcriptional repressors that suppress c-Myc dependent transformation and are expressed during neural and epidermal differentiation. EMBO Journal 22, 5646–5659
    OpenUrl
    1. Jenkins N. A.,
    2. Copeland N. G.,
    3. Taylor B. A.,
    4. Lee B. K.
    (1982) Organization, distribution and stability of endogenous ecotropic murine leukemia virus DNA sequences in chromosomes of Mus musculus. J. Virol 43, 26–36
    OpenUrlAbstract/FREE Full Text
    1. Kozak M.
    (1987) At least six nucleotides preceding the AUG initiator codon enhance translation in mammalian cells. J. Mol. Biol 196, 947–950
    OpenUrlCrossRefPubMedWeb of Science
    1. Laird P. W.,
    2. Zijderveld A.,
    3. Linders K.,
    4. Rudnicki M. A.,
    5. Jaenisch R.,
    6. Berns A.
    (1991) Simplified mammalian DNA isolation procedure. Nucleic Acids Res 19, 4293–.
    OpenUrlFREE Full Text
    1. Luo J.,
    2. Sladek R.,
    3. Bader J.-A.,
    4. Matthyssen A. R. J.,
    5. Giguere V.
    (1997) Placental abnormalities in mouse embryos lacking the orphan nuclear receptor ERR-. Nature 388, 778–782
    OpenUrlCrossRefPubMed
    1. Mano H.,
    2. Ishikawa F.,
    3. Nishida J.,
    4. Hirai H.,
    5. Takaku F.
    (1990) A novel protein-tyrosine kinase, tec, is preferentially expressed in liver. Oncogene 5, 1781–1786
    OpenUrlPubMedWeb of Science
    1. Moore K. J.
    (1995) Insight into the microphthalmia gene. Trends Genet 11, 442–448
    OpenUrlCrossRefPubMedWeb of Science
    1. Nagy A.,
    2. Gocza E.,
    3. Diaz E. M.,
    4. Prideaux V. R.,
    5. Iványi E.,
    6. Markkula M.,
    7. Rossant J.
    (1990) Embryonic stem cells alone are able to support fetal development in the mouse. Development 110, 815–821
    OpenUrlAbstract/FREE Full Text
    1. Pazin M. J.,
    2. Kadonaga J. T.
    (1997) What's up and down with histone deacetylation and transcription. Cell 89, 325–328
    OpenUrlCrossRefPubMedWeb of Science
    1. Schmidt C.,
    2. Bladt F.,
    3. Goedecke S.,
    4. Brinkmann V.,
    5. Zschiesche W.,
    6. Sharpe M.,
    7. Gherardi E.,
    8. Birchmeier C.
    (1995) Scatter factor/hepatocyte growth factor is essential for liver development. Nature 373, 699–702
    OpenUrlCrossRefPubMed
    1. Shweiki D.,
    2. Itin A.,
    3. Neufeld G.,
    4. Gitay-Goren H.,
    5. Keshet E.
    (1993) Patterns of expression of vascular endothelial growth factor (VEGF) and VEGF receptors in mice suggest a role in hormonally regulated angiogenesis. J. Clin. Invest 91, 2235–2243
    1. Siracusa L. D.,
    2. Russell L. B.,
    3. Jenkins N. A.,
    4. Copeland N. G.
    (1987) Allelic variation within the Emv-15 locus defines genomic sequences closely linked to the agouti locus on mouse chromosome 2. Genetics 117, 85–92
    OpenUrlAbstract/FREE Full Text
    1. Soriano P.,
    2. Montgomery C.,
    3. Geske R.,
    4. Bradley A.
    (1991) Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell 64, 693–702
    OpenUrlCrossRefPubMedWeb of Science
    1. Steingrímsson E.,
    2. Moore K. J.,
    3. Lamoreux M. L.,
    4. Ferre-D'Amare A. R.,
    5. Burley S. K.,
    6. Zimring D. C.,
    7. Skow L. C.,
    8. Hodgkinson C. A.,
    9. Arnheiter H.,
    10. Copeland N. G.,
    11. Jenkins N. A.
    (1994) Molecular basis of mouse microphthalmia (mi) mutations helps explain their developmental and phenotypic consequences. Nat. Genet 8, 256–63
    OpenUrlCrossRefPubMedWeb of Science
    1. Steingrímsson E.,
    2. Nii A.,
    3. Fisher D. E.,
    4. Ferre-D'Amare A. R.,
    5. McCormick R. J.,
    6. Russell L. B.,
    7. Burley S. K.,
    8. Ward J. M.,
    9. Jenkins N. A.,
    10. Copeland N. G.
    (1996) The semidominant Mib mutation identifies a role for the HLH domain in DNA binding in addition to its role in protein dimerization. EMBO J 15, 6280–6289
    OpenUrlPubMedWeb of Science
    1. Swiatek P. J.,
    2. Gridley T.
    (1993) Perinatal lethality and defects in hindbrain development in mice homozygous for a targeted mutation of the zinc finger gene Krox20. Genes Dev 7, 2071–2084
    OpenUrlAbstract/FREE Full Text
    1. Tanaka M.,
    2. Gertsenstein M.,
    3. Rossant J.,
    4. Nagy A.
    (1997) Mash2 acts cell autonomously in mouse spongiotrophoblast development. Dev. Biol 190, 55–65
    OpenUrlCrossRefPubMedWeb of Science
    1. Tessarollo L.,
    2. Parada L. F.
    (1995) In situ hybridization. Methods in Enzymology 254, 419–430
    OpenUrlPubMedWeb of Science
    1. Uehara Y.,
    2. Minowa O.,
    3. Mori C.,
    4. Shiota K.,
    5. Kuno J.,
    6. Noda T.,
    7. Kitamura N.
    (1995) Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor. Nature 373, 702–705
    OpenUrlCrossRefPubMedWeb of Science
    1. Vecchi A.,
    2. Garlanda C.,
    3. Lampugnani M. G.,
    4. Resnati M.,
    5. Mettucci C.,
    6. Stoppacciaro A.,
    7. Schnurch H.,
    8. Risau W.,
    9. Ruco L.,
    10. Mantovani A.,
    11. Dejana E.
    (1994) Monoclonal antibodies specific for endothelial cells of mouse blood vessels. Their application in the identification of adult and embryonic endothelium. Eur. J. Cell Biol 63, 247–254
    OpenUrlPubMedWeb of Science
    1. Weterman M. A. J.,
    2. Wilbrink M.,
    3. van Kessel A. G.
    (1996) Fusion of the transcription factor TFE3 gene to a novel gene, PRCC, in t(X;1)(p11;q21)-positive papillary renal cell carcinomas. Proc. Natl. Acad. Sci. USA 93, 15294–15298
    OpenUrlAbstract/FREE Full Text
    1. Yamaguchi T. P.,
    2. Dumont D.,
    3. Conlon R. A.,
    4. Breitman M. L.,
    5. Rossant J.
    (1993) flk-1, an flt -related receptor tyrosine kinase is an early marker for endothelial cell precursors. Development 118, 489–498
    OpenUrlAbstract
    1. Yasumoto K.,
    2. Shibahara S.
    (1997) Molecular cloning of a cDNA encoding a human TFEC isoform, a newly identified transcriptional regulator. Biochim. Biophys. Acta 1353, 23–31
    OpenUrlPubMed
    1. Zervos A. S.,
    2. Gyuris J.,
    3. Brent R.
    (1993) Mxi1, a protein that specifically interacts with Max to bind Myc-Max recognition sites. Cell 72, 223–232
    OpenUrlCrossRefPubMedWeb of Science
    1. Zhao G.-Q.,
    2. Zhao Q.,
    3. Zhou X.,
    4. Mattei M.-G.,
    5. DeCrombrugghe B.
    (1993) TFEC, a basic helix-loop-helix protein, forms heterodimers with TFE3 and inhibits TFE3-dependent transcription activation. Mol. Cell. Biol 13, 4505–4512
    OpenUrlAbstract/FREE Full Text
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JOURNAL ARTICLES
The bHLH-Zip transcription factor Tfeb is essential for placental vascularization
E. Steingrimsson, L. Tessarollo, S.W. Reid, N.A. Jenkins, N.G. Copeland
Development 1998 125: 4607-4616;
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JOURNAL ARTICLES
The bHLH-Zip transcription factor Tfeb is essential for placental vascularization
E. Steingrimsson, L. Tessarollo, S.W. Reid, N.A. Jenkins, N.G. Copeland
Development 1998 125: 4607-4616;

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