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JOURNAL ARTICLES
Targeted disruption of the Wnt2 gene results in placentation defects
S.J. Monkley, S.J. Delaney, D.J. Pennisi, J.H. Christiansen, B.J. Wainwright
Development 1996 122: 3343-3353;

Summary

Wnt genes have been implicated in a range of developmental processes in the mouse including the patterning of the central nervous system and limbs. Reported here for the first time is the expression of Wnt2 in the early heart field of 7.5-8.5 dpc (days post-coitum) mouse embryos, making Wnt2 a potentially useful gene marker for the early stages of heart development. Expression was also detected in the allantois from 8.0 dpc and at later stages in the placenta and umbilicus. Mice deficient in Wnt2, generated by gene targeting, displayed runting and approximately 50% died perinatally. Histological analysis revealed alterations in the size and structure of placentas from these mice from 14.5 dpc. The placental defects were associated primarily with the labyrinthine zone and included oedema and tissue disruption and accumulation of maternal blood in large pools. There was also an apparent decrease in the number of foetal capillaries and an increase in the amount of fibrinoid material in the Wnt2 mutant placentas. These results suggest that Wnt2 is required for the proper vascularisation of the mouse placenta and the placental defects in Wnt2-deficient mice result in a reduction in birthweight and perinatal lethality.

Reference

    1. Augustine K.,
    2. Liu E. T.,
    3. Sadler T. W.
    (1993) Antisense attenuation of Wnt −1 and Wnt −3a expression in whole embryo culture reveals roles for these genes in craniofacial, spinal cord and cardiac morphogenesis. Dev. Genet 14, 500–520
    OpenUrlCrossRefPubMedWeb of Science
    1. Augustine K. A.,
    2. Liu E. T.,
    3. Sadler T. W.
    (1995) Interactions of Wnt −1 and Wnt −3a are essential for neural tube patterning. Teratology 51, 107–119
    OpenUrlCrossRefPubMed
    1. Bellusci S.,
    2. Henderson R.,
    3. Winnier G.,
    4. Oikawa T.,
    5. Hogan B. L. M.
    (1996) Evidence from normal expression and targeted misexpression that Bone Morphogenic Protein-4 (Bmp-4) plays a role in mouse embryonic lung morphogenesis. Development 122, 1693–1702
    OpenUrlAbstract
    1. Boyd P. A.,
    2. Scott A.
    (1985) Quantitative structural studies on human placentas associated with pre-eclampsia, essential hypertension and intrauterine growth retardation. Bri. J. Obstet. Gynaecol 92, 714–721
    OpenUrlPubMedWeb of Science
    1. Buhler T. A.,
    2. Dale T. C.,
    3. Kieback C.,
    4. Humphreys R. C.,
    5. Rosen J. M.
    (1993) Localization and quantification of Wnt −2 gene expression in mouse mammary development. Dev. Biol 155, 87–96
    OpenUrlCrossRefPubMed
    1. Christiansen J. H.,
    2. Dennis C. L.,
    3. Wicking C. A.,
    4. Monkley S. J.,
    5. Wilkinson D. G.,
    6. Wainwright B. J.
    (1995) Murine Wnt −11 and Wnt −12 have temporally and spatially restricted expression patterns during embryonic development. Mech. Dev 51, 341–350
    OpenUrlCrossRefPubMedWeb of Science
    1. Chu-LeGraff Q.,
    2. Doe C. Q.
    (1993) Neuroblast specification and formation regulated by wingless in the Drosophila CNS. Science 261, 1594–1597
    OpenUrlAbstract/FREE Full Text
    1. Couso J. P.,
    2. Bate M.,
    3. Martinez-Arias A.
    (1993) A wingless -dependent polar co-ordinate system in Drosophila imaginal discs. Science 259, 484–489
    OpenUrlAbstract/FREE Full Text
    1. Ellington S. K. L.
    (1985) A morphological study of the development of the allantois of rat embryos in vivo. J. Anat 142, 1–11
    OpenUrlPubMed
    1. Frank H. G.,
    2. Malekzadeh F.,
    3. Kertschanska S.,
    4. Crescimanno C.,
    5. Castellucci M.,
    6. Lang I.,
    7. Desoye G.,
    8. Kaufmann P.
    (1994) Immunohistochemistry of two different types of placental fibrinoid. Acta Anat 150, 55–68
    OpenUrlPubMedWeb of Science
    1. Gavin B. J.,
    2. McMahon J. A.,
    3. McMahon A. P.
    (1990) Expression of multiple novel Wnt −1/ int −1-related genes during fetal and adult mouse development. Genes Dev 4, 2319–2332
    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. Gurtner G. C.,
    2. Davis V.,
    3. Li H.,
    4. McCoy M. J.,
    5. Sharpe A.,
    6. Cybulsky M. I.
    (1995) Targeted disruption of the murine VCAM1 gene: essential role of VCAM-1 in chorioallantoic fusion and placentation. Genes Dev 9, 1–14
    OpenUrlAbstract/FREE Full Text
    1. Kostriken R.,
    2. Weisblat D. A.
    (1992) Expression of a Wnt gene in embryonic epithelium of the leech. Dev. Biol 151, 225–2241
    OpenUrlCrossRefPubMed
    1. Levay-Young B. K.,
    2. Navre M.
    (1992) Growth and developmental regulation of wnt-2 (irp) gene in mesenchymal cells of fetal lung. Am. J. Physiol 262, 672–.
    OpenUrl
    1. Mansour S. L.,
    2. Thomas K. R.,
    3. Capecchi M. C.
    (1988) Disruption of the proto-oncogene int −2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Nature 336, 348–352
    OpenUrlCrossRefPubMed
    1. McMahon A. P.,
    2. Bradley A.
    (1990) The Wnt −1 (int −1) proto-oncogene is required for development of a large region of the mouse brain. Cell 62, 1073–1085
    OpenUrlCrossRefPubMedWeb of Science
    1. McMahon A. P.,
    2. Joyner A. L.,
    3. Bradley A.,
    4. McMahon J. A.
    (1992). The midbrain-hindbrain phenotype of Wnt −1-/ Wnt −1-mice results from stepwise deletion of engrailed-expressing cells by 9.5 days postcoitum. Cell 69, 581–595
    OpenUrlCrossRefPubMedWeb of Science
    1. McMahon J. A.,
    2. McMahon A. P.
    (1989) Nucleotide sequence, chromosomal localization and developmental expression of the mouse int-1-related gene. Development 107, 643–650
    OpenUrlAbstract
    1. Parr B. A.,
    2. Shea M. J.,
    3. Vassileva G.,
    4. McMahon A. P.
    (1993) Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds. Development 119, 247–261
    OpenUrlAbstract
    1. Redline R. W.
    (1995) Placental pathology—a neglected link between basic disease mechanisms and untoward pregnancy outcome. Curr. Opin. Obstet. Gynecol 7, 10–15
    OpenUrlPubMedWeb of Science
    1. Rijsewijk F.,
    2. Schuermann M.,
    3. Wagenaar E.,
    4. Parren P.,
    5. Weigel D.,
    6. Nusse R.
    (1987) The Drosophila homolog of the mouse mammary oncogene int −1 is identical to the segment polarity gene wingless. Cell 50, 649–657
    OpenUrlCrossRefPubMedWeb of Science
    1. Roelink H.,
    2. Wagenaar E.,
    3. Nusse R.
    (1992) Amplification and proviral activation of several Wnt genes during progression and clonal variation of mouse mammary tumors. Oncogene 7, 487–492
    OpenUrlPubMed
    1. Schaeren-Wiemers N.,
    2. Gerfin-Moser A.
    (1993) A single protocol to detect transcripts of various types and expression levels in neural tissue and cultured cells: in situ hybridization using digoxygenin-labelled cDNA probes. Histochemistry 100, 431–440
    OpenUrlCrossRefPubMedWeb of Science
    1. Sidow A.
    (1992) Diversification of the Wnt gene family on the ancestral lineage of vertebrates. Proc. Natl. Acad. Sci. USA 89, 5098–5102
    OpenUrlAbstract/FREE Full Text
    1. Skaer H.,
    2. Martinez Arias A.
    (1992) The wingless product is required for cell proliferation in the Malpighian tubule anlage of Drosophila melanogaster. Development 116, 745–754
    OpenUrlAbstract
    1. Stark K.,
    2. Vainio S.,
    3. Vassileva G.,
    4. McMahon A. P.
    (1994) Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt −4. Nature 372, 679–683
    OpenUrlCrossRefPubMedWeb of Science
    1. Takada S.,
    2. Stark K. L.,
    3. Shea M. J.,
    4. Vassileva G.,
    5. McMahon J. A.,
    6. McMahon A. P.
    (1994) Wnt −3a regulates somite and tailbud formation in the mouse embryo. Genes Dev 8, 174–189
    OpenUrlAbstract/FREE Full Text
    1. Thomas K. R.,
    2. Capecchi M. R.
    (1990) Targeted disruption of the murine int −1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development. Nature 346, 847–850
    OpenUrlCrossRefPubMedWeb 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. van Ooyen A.,
    2. Nusse R.
    (1984) Structure and nucleotide sequence of the putative mammary oncogene int −1; Proviral insertions leave the protein-encoding domain intact. Cell 39, 233–240
    OpenUrlCrossRefPubMedWeb of Science
    1. Wainwright B. J.,
    2. Scambler P. J.,
    3. Stanier P.,
    4. Watson E. K.,
    5. Bell G.,
    6. Wicking C.,
    7. Estivill X.,
    8. Courtney M.,
    9. Boue A.,
    10. Pederson P. S.,
    11. Williamson R.,
    12. Farrall M.
    (1988) Isolation of a human gene with protein sequence similarity to human and murine int −1 and Drosophila segment polarity mutant wingless. EMBO J 7, 1743–1748
    OpenUrlPubMedWeb of Science
    1. Ware C. B.,
    2. Horowitz M. C.,
    3. Renshaw B. R.,
    4. Hunt J. S.,
    5. Liggitt D.,
    6. Koblar S. A.,
    7. Gliniak B. C.,
    8. Mckenna H. J.,
    9. Papayannopoulou T.,
    10. Thoma B.,
    11. Cheng L. Z.,
    12. Donovan P. J.,
    13. Peschon J. J.,
    14. Bartlett P. F.,
    15. Willis C. R.,
    16. Wright B. D.,
    17. Carpenter M. K.,
    18. Davison B. L.,
    19. Gearing D. P.
    (1995) Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death. Development 121, 1283–1299
    OpenUrlAbstract
    1. Weber-Hall S. J.,
    2. Phippard D. J.,
    3. Niemeyer C. C.,
    4. Dale T. C.
    (1994) Developmental and hormonal regulation of Wnt gene expression in the mouse mammary gland. Differentiation 57, 205–214
    OpenUrlCrossRefPubMedWeb of Science
    1. Wu X. S.,
    2. Golden K.,
    3. Bodmer R.
    (1995) Heart development in Drosophila requires the segment polarity gene wingless. Dev. Biol 169, 619–628
    OpenUrlCrossRefPubMedWeb of Science
    1. Yang J. T.,
    2. Rayburn H.,
    3. Hynes R. O.
    (1995) Cell adhesion events mediated by(4) integrins are essential in placental and cardiac development. Development 121, 549–560
    OpenUrlAbstract
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JOURNAL ARTICLES
Targeted disruption of the Wnt2 gene results in placentation defects
S.J. Monkley, S.J. Delaney, D.J. Pennisi, J.H. Christiansen, B.J. Wainwright
Development 1996 122: 3343-3353;
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