Gene Symbol: Tpbpa
Description: trophoblast specific protein alpha
Alias: AV033951, Tb-1, Tb1, Tpbp, b2b1247Clo, trophoblast-specific protein alpha, Mutant line 1247, clone 4311
Species: mouse
Products:     Tpbpa

Top Publications

  1. Dupressoir A, Vernochet C, Harper F, Guégan J, Dessen P, Pierron G, et al. A pair of co-opted retroviral envelope syncytin genes is required for formation of the two-layered murine placental syncytiotrophoblast. Proc Natl Acad Sci U S A. 2011;108:E1164-73 pubmed publisher
    ..Although some are absolutely required for completion of pregnancy, others are still amenable to "epigenetic" compensations, thus illustrating the complexity of the molecular machinery that developed during placental evolution. ..
  2. Lescisin K, Varmuza S, Rossant J. Isolation and characterization of a novel trophoblast-specific cDNA in the mouse. Genes Dev. 1988;2:1639-46 pubmed
    ..The role of the gene is not currently known, but the presence of a signal peptide suggests that it may be a secreted protein. ..
  3. Morasso M, Grinberg A, Robinson G, Sargent T, Mahon K. Placental failure in mice lacking the homeobox gene Dlx3. Proc Natl Acad Sci U S A. 1999;96:162-7 pubmed
  4. Schorpp Kistner M, Wang Z, Angel P, Wagner E. JunB is essential for mammalian placentation. EMBO J. 1999;18:934-48 pubmed
    ..Therefore, JunB appears to be involved in multiple signaling pathways regulating genes involved in the establishment of a proper feto-maternal circulatory system. ..
  5. Guillemot F, Nagy A, Auerbach A, Rossant J, Joyner A. Essential role of Mash-2 in extraembryonic development. Nature. 1994;371:333-6 pubmed
    ..Mash-2 is the first transcription factor shown to play a critical part in the development of the mammalian trophoblast lineage. ..
  6. Shaut C, Keene D, Sorensen L, Li D, Stadler H. HOXA13 Is essential for placental vascular patterning and labyrinth endothelial specification. PLoS Genet. 2008;4:e1000073 pubmed publisher
  7. Kraut N, Snider L, Chen C, Tapscott S, Groudine M. Requirement of the mouse I-mfa gene for placental development and skeletal patterning. EMBO J. 1998;17:6276-88 pubmed
    ..Our results indicate that I-mfa plays an important role in trophoblast and chondrogenic differentiation by negatively regulating a subset of lineage-restricted bHLH proteins. ..
  8. Schreiber M, Wang Z, Jochum W, Fetka I, Elliott C, Wagner E. Placental vascularisation requires the AP-1 component fra1. Development. 2000;127:4937-48 pubmed
    ..In contrast, the spongiotrophoblast layer was unaffected and expressed the marker genes 4311 (Tpbp) and Flt1...
  9. Mudgett J, Ding J, Guh Siesel L, Chartrain N, Yang L, Gopal S, et al. Essential role for p38alpha mitogen-activated protein kinase in placental angiogenesis. Proc Natl Acad Sci U S A. 2000;97:10454-9 pubmed
    ..Thus, our results indicate a requirement for p38alpha MAPK in diploid trophoblast development and placental vascularization and suggest a more general role for p38 MAPK signaling in embryonic angiogenesis. ..

More Information


  1. Frank D, Mendelsohn C, Ciccone E, Svensson K, Ohlsson R, Tycko B. A novel pleckstrin homology-related gene family defined by Ipl/Tssc3, TDAG51, and Tih1: tissue-specific expression, chromosomal location, and parental imprinting. Mamm Genome. 1999;10:1150-9 pubmed
    ..The data also define a new subfamily of PH domain genes. ..
  2. Basyuk E, Cross J, Corbin J, Nakayama H, Hunter P, Nait Oumesmar B, et al. Murine Gcm1 gene is expressed in a subset of placental trophoblast cells. Dev Dyn. 1999;214:303-11 pubmed
    ..5 within a subset of labyrinthine trophoblast cells. Comparison with other transcription factors revealed that Gcm1 expression defines a unique subset of trophoblast cells. ..
  3. Fischer A, Schumacher N, Maier M, Sendtner M, Gessler M. The Notch target genes Hey1 and Hey2 are required for embryonic vascular development. Genes Dev. 2004;18:901-11 pubmed
    ..This indicates that Hey1/Hey2 are essential transducers of Notch signals in cardiovascular development that may mediate arterial cell fate decision. ..
  4. Katsanou V, Milatos S, Yiakouvaki A, Sgantzis N, Kotsoni A, Alexiou M, et al. The RNA-binding protein Elavl1/HuR is essential for placental branching morphogenesis and embryonic development. Mol Cell Biol. 2009;29:2762-76 pubmed publisher
    ..Collectively, our data demonstrate the dominant role of HuR in organizing gene expression programs guiding placental labyrinth morphogenesis, skeletal specification patterns, and splenic ontogeny. ..
  5. van Nes J, de Graaff W, Lebrin F, Gerhard M, Beck F, Deschamps J. The Cdx4 mutation affects axial development and reveals an essential role of Cdx genes in the ontogenesis of the placental labyrinth in mice. Development. 2006;133:419-28 pubmed
    ..Cdx genes thus operate in a redundant way during placentogenesis, as they do during embryonic axial elongation and patterning, and independently from the previously reported early Cdx2-specific role in the trophectoderm at implantation...
  6. Finkenzeller D, Fischer B, Lutz S, Schrewe H, Shimizu T, Zimmermann W. Carcinoembryonic antigen-related cell adhesion molecule 10 expressed specifically early in pregnancy in the decidua is dispensable for normal murine development. Mol Cell Biol. 2003;23:272-9 pubmed
    ..Taken together, both Ceacam10 and Ceacam9, alone or in combination, are not essential for either murine placental and embryonic development or for adult life. ..
  7. Riley P, Anson Cartwright L, Cross J. The Hand1 bHLH transcription factor is essential for placentation and cardiac morphogenesis. Nat Genet. 1998;18:271-5 pubmed
    ..Their heart tubes showed abnormal looping and ventricular myocardial differentiation. Therefore, Hand1 is essential for differentiation of both trophoblast and cardiomyocytes, which are embryologically distinct cell lineages. ..
  8. Giroux S, Tremblay M, Bernard D, Cardin Girard J, Aubry S, Larouche L, et al. Embryonic death of Mek1-deficient mice reveals a role for this kinase in angiogenesis in the labyrinthine region of the placenta. Curr Biol. 1999;9:369-72 pubmed
    ..They also suggest that mek1 function is required for normal response to angiogenic signals that might promote vascularization of the labyrinthine region of the placenta. ..
  9. Oh McGinnis R, Bogutz A, Lefebvre L. Partial loss of Ascl2 function affects all three layers of the mature placenta and causes intrauterine growth restriction. Dev Biol. 2011;351:277-86 pubmed publisher
  10. Tunster S, Tycko B, John R. The imprinted Phlda2 gene regulates extraembryonic energy stores. Mol Cell Biol. 2010;30:295-306 pubmed publisher
    ..In addition, glycogen cells do not migrate into the maternal decidua in a timely fashion, but instead, Tpbpa-positive cells progressively mislocalize into the labyrinth...
  11. Adamson S, Lu Y, Whiteley K, Holmyard D, Hemberger M, Pfarrer C, et al. Interactions between trophoblast cells and the maternal and fetal circulation in the mouse placenta. Dev Biol. 2002;250:358-73 pubmed
    ..5. These cells did not express Plf, but rather expressed the spongiotrophoblast-specific gene Tpbp. Dilation of the spiral arteries was obvious between E10.5 and E14...
  12. Chen H, Detmer S, Ewald A, Griffin E, Fraser S, Chan D. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol. 2003;160:189-200 pubmed
    ..Therefore, mitochondrial fusion is essential for embryonic development, and by enabling cooperation between mitochondria, has protective effects on the mitochondrial population. ..
  13. Monkley S, Delaney S, Pennisi D, Christiansen J, Wainwright B. Targeted disruption of the Wnt2 gene results in placentation defects. Development. 1996;122:3343-53 pubmed
    ..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. ..
  14. Withington S, Scott A, Saunders D, Lopes Floro K, Preis J, Michalicek J, et al. Loss of Cited2 affects trophoblast formation and vascularization of the mouse placenta. Dev Biol. 2006;294:67-82 pubmed
    ..We conclude that Cited2 is required for normal placental development and vascularisation, and hence for embryo viability. ..
  15. Li Y, Behringer R. Esx1 is an X-chromosome-imprinted regulator of placental development and fetal growth. Nat Genet. 1998;20:309-11 pubmed
    ..These results identify Esx1 as the first essential X-chromosome-imprinted regulator of placental development that influences fetal growth, and may aid our understanding human placental insufficiency syndromes. ..
  16. Ono R, Nakamura K, Inoue K, Naruse M, Usami T, Wakisaka Saito N, et al. Deletion of Peg10, an imprinted gene acquired from a retrotransposon, causes early embryonic lethality. Nat Genet. 2006;38:101-6 pubmed
    ..This indicates that Peg10 is critical for mouse parthenogenetic development and provides the first direct evidence of an essential role of an evolutionarily conserved retrotransposon-derived gene in mammalian development...
  17. Tanaka H, Nagaike K, Takeda N, Itoh H, Kohama K, Fukushima T, et al. Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is required for branching morphogenesis in the chorioallantoic placenta. Mol Cell Biol. 2005;25:5687-98 pubmed
    ..Our results indicate that mouse HAI-1 is essential for branching morphogenesis in the chorioallantoic placenta and lack of HAI-1 function may result in placental failure. ..
  18. Tai Nagara I, Yoshikawa Y, Numata N, Ando T, Okabe K, Sugiura Y, et al. Placental labyrinth formation in mice requires endothelial FLRT2/UNC5B signaling. Development. 2017;144:2392-2401 pubmed publisher
    ..Our results suggest that the proper organization of the placental labyrinth depends on coordinated inter-endothelial repulsion, which prevents uncontrolled layering of the endothelium. ..
  19. Iwawaki T, Akai R, Yamanaka S, Kohno K. Function of IRE1 alpha in the placenta is essential for placental development and embryonic viability. Proc Natl Acad Sci U S A. 2009;106:16657-62 pubmed publisher
    ..These findings reveal that IRE1alpha plays an essential function in extraembryonic tissues and highlight the relationship of physiological ER stress and angiogenesis in the placenta during pregnancy in mammals. ..
  20. Lo H, Tsai C, Chen C, Wang L, Lee Y, Chen C, et al. Association of dysfunctional synapse defective 1 (SYDE1) with restricted fetal growth - SYDE1 regulates placental cell migration and invasion. J Pathol. 2017;241:324-336 pubmed publisher
    ..Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. ..
  21. Yan L, Carr J, Ashby P, Murry Tait V, Thompson C, Arthur J. Knockout of ERK5 causes multiple defects in placental and embryonic development. BMC Dev Biol. 2003;3:11 pubmed
    ..Erk5 is essential for early embryonic development, and is required for normal development of the vascular system and cell survival. ..
  22. Rantakari P, Strauss L, Kiviranta R, Lagerbohm H, Paviala J, Holopainen I, et al. Placenta defects and embryonic lethality resulting from disruption of mouse hydroxysteroid (17-beta) dehydrogenase 2 gene. Mol Endocrinol. 2008;22:665-75 pubmed
    ..Our results provide evidence for a role for HSD17B2 enzyme in the cellular organization of the mouse placenta. ..
  23. Keniry A, Oxley D, Monnier P, Kyba M, Dandolo L, Smits G, et al. The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and Igf1r. Nat Cell Biol. 2012;14:659-65 pubmed publisher
    ..The controlled release of miR-675 from H19 may also allow rapid inhibition of cell proliferation in response to cellular stress or oncogenic signals. ..
  24. Um S, Sticker Jantscheff M, Chau G, Vintersten K, Mueller M, Gangloff Y, et al. S6K1 controls pancreatic ? cell size independently of intrauterine growth restriction. J Clin Invest. 2015;125:2736-47 pubmed publisher
    ..Together, these data suggest that a nutrient-mediated reduction in intrinsic ? cell S6K1 signaling, rather than IUGR, during fetal development may underlie reduced ? cell growth and eventual development of T2DM later in life. ..
  25. Pitman J, Lin T, Kleeman J, Erickson G, MacLeod C. Normal reproductive and macrophage function in Pem homeobox gene-deficient mice. Dev Biol. 1998;202:196-214 pubmed
    ..Together, these data show that Pem is dispensable for embryonic and postnatal development, gonadal function, and Kupffer cell activation, perhaps due to compensatory expression of a similar homeobox gene. ..
  26. Ng R, Dean W, Dawson C, Lucifero D, Madeja Z, Reik W, et al. Epigenetic restriction of embryonic cell lineage fate by methylation of Elf5. Nat Cell Biol. 2008;10:1280-90 pubmed publisher
    ..This epigenetic restriction of cell lineage fate provides a molecular mechanism for Waddington's concept of canalization of developmental pathways. ..
  27. Mainigi M, Olalere D, Burd I, Sapienza C, Bartolomei M, Coutifaris C. Peri-implantation hormonal milieu: elucidating mechanisms of abnormal placentation and fetal growth. Biol Reprod. 2014;90:26 pubmed publisher
  28. Branco M, King M, Perez García V, Bogutz A, Caley M, Fineberg E, et al. Maternal DNA Methylation Regulates Early Trophoblast Development. Dev Cell. 2016;36:152-63 pubmed publisher
    ..Our results reveal that maternal DNA methylation controls multiple differentiation-related and physiological processes in trophoblast via both imprinting-dependent and -independent mechanisms. ..
  29. Shi W, van den Hurk J, Alamo Bethencourt V, Mayer W, Winkens H, Ropers H, et al. Choroideremia gene product affects trophoblast development and vascularization in mouse extra-embryonic tissues. Dev Biol. 2004;272:53-65 pubmed
    ..spretus X-chromosome rather than a modifier effect. Our results demonstrate that Chm is essential for diploid trophoblast development and plays a role in the vascularization in placenta and yolk sac. ..
  30. Zwart R, Verhaagh S, De Jong J, Lyon M, Barlow D. Genetic analysis of the organic cation transporter genes Orct2/Slc22a2 and Orct3/Slc22a3 reduces the critical region for the t haplotype mutant t(w73) to 200 kb. Mamm Genome. 2001;12:734-40 pubmed
    ..The results eliminate both Orct2 and Orct3 as candidates and further reduce the critical region containing the t(w73) mutant from 500 kb to 200 kb. ..
  31. Hamada Y, Hiroe T, Suzuki Y, Oda M, Tsujimoto Y, Coleman J, et al. Notch2 is required for formation of the placental circulatory system, but not for cell-type specification in the developing mouse placenta. Differentiation. 2007;75:268-78 pubmed
    ..Thus, Notch2 is not cell autonomously required for the early cell fate determination of subtypes of trophoblast cells, but plays an indispensable role in the formation of maternal blood sinuses in the developing mouse placenta. ..
  32. Petit F, Jamin S, Kurihara I, Behringer R, DeMayo F, Tsai M, et al. Deletion of the orphan nuclear receptor COUP-TFII in uterus leads to placental deficiency. Proc Natl Acad Sci U S A. 2007;104:6293-8 pubmed
    ..The endometrial COUP-TFII might modulate the signaling between the uterus and the extraembryonic tissue for the proper formation of the placenta. ..
  33. Saito K, Ogawa A, Toyofuku K, Hosoi Y, Soma M, Iha M, et al. Relationships between homeoprotein EGAM1C and the expression of the placental prolactin gene family in mouse placentae and trophoblast stem cells. Reproduction. 2011;141:259-68 pubmed publisher
    ..These results indicated that EGAM1C may play a role in the expression of members of the placental PRL gene family, such as Prl3b1 and Prl5a1. ..
  34. Teesalu T, Blasi F, Talarico D. Expression and function of the urokinase type plasminogen activator during mouse hemochorial placental development. Dev Dyn. 1998;213:27-38 pubmed
    ..The function of uPA in trophoblast invasion appears not to be indispensable, and its absence can be overcome by redundant or compensatory mechanisms. ..
  35. Mayer W, Hemberger M, Frank H, Grummer R, Winterhager E, Kaufmann P, et al. Expression of the imprinted genes MEST/Mest in human and murine placenta suggests a role in angiogenesis. Dev Dyn. 2000;217:1-10 pubmed dyn 2000;217:1-10. ..
  36. Wessells J, Wessner D, Parsells R, White K, Finkenzeller D, Zimmermann W, et al. Pregnancy specific glycoprotein 18 induces IL-10 expression in murine macrophages. Eur J Immunol. 2000;30:1830-40 pubmed
    ..Taken together, these results suggest that PSG18 selectively up-regulates IL-10 production by macrophages, providing a possible mechanism by which this protein helps promote successful pregnancy. ..
  37. Mugford J, Yee D, Magnuson T. Failure of extra-embryonic progenitor maintenance in the absence of dosage compensation. Development. 2012;139:2130-8 pubmed publisher
    ..Conversely, unlike the epiblast, in which XCI is not required for progenitor cell maintenance, we demonstrate that dosage compensation is indispensable for the maintenance of trophoblast progenitors. ..
  38. Voss A, Thomas T, Gruss P. Mice lacking HSP90beta fail to develop a placental labyrinth. Development. 2000;127:1-11 pubmed
    ..The allantois mesoderm is thought to induce trophoblast differentiation. Our results show that Hsp90beta is a necessary component of this induction process. ..
  39. Landles C, Chalk S, Steel J, Rosewell I, Spencer Dene B, Lalani E, et al. The thyroid hormone receptor-associated protein TRAP220 is required at distinct embryonic stages in placental, cardiac, and hepatic development. Mol Endocrinol. 2003;17:2418-35 pubmed
    ..5, with an additional requirement in embryonic tissues for hepatic and cardiovascular development thereafter. ..
  40. Finkenzeller D, Fischer B, McLaughlin J, Schrewe H, Ledermann B, Zimmermann W. Trophoblast cell-specific carcinoembryonic antigen cell adhesion molecule 9 is not required for placental development or a positive outcome of allotypic pregnancies. Mol Cell Biol. 2000;20:7140-5 pubmed
    ..Taken together, Ceacam9 is dispensable for murine placental and embryonic development despite being highly conserved within rodents. ..
  41. Cowden Dahl K, Fryer B, Mack F, Compernolle V, Maltepe E, Adelman D, et al. Hypoxia-inducible factors 1alpha and 2alpha regulate trophoblast differentiation. Mol Cell Biol. 2005;25:10479-91 pubmed
    ..This novel genetic approach provides new insights into the role of O2 tension in the development of life-threatening pregnancy-related diseases such as preeclampsia. ..
  42. Nadeau V, Guillemette S, Bélanger L, Jacob O, Roy S, Charron J. Map2k1 and Map2k2 genes contribute to the normal development of syncytiotrophoblasts during placentation. Development. 2009;136:1363-74 pubmed publisher
    ..Thus, even though Map2k1 plays a predominant role, these results enlighten the function of Map2k2 in placenta development. ..
  43. Teesalu T, Masson R, Basset P, Blasi F, Talarico D. Expression of matrix metalloproteinases during murine chorioallantoic placenta maturation. Dev Dyn. 1999;214:248-58 pubmed
    ..Our findings document the participation of MMPs and their inhibitors in the process of late murine placenta maturation, and warrant the characterization of other members of the MMP family, like membrane type-MMPs, in this process. ..
  44. Appelbe O, Yevtodiyenko A, Muniz Talavera H, Schmidt J. Conditional deletions refine the embryonic requirement for Dlk1. Mech Dev. 2013;130:143-59 pubmed publisher
    ..Dlk1(flox) mice will continue to provide an important tool for further research into the function of Dlk1. ..
  45. Himes K, Koppes E, Chaillet J. Generalized disruption of inherited genomic imprints leads to wide-ranging placental defects and dysregulated fetal growth. Dev Biol. 2013;373:72-82 pubmed publisher
  46. Parr B, Cornish V, Cybulsky M, McMahon A. Wnt7b regulates placental development in mice. Dev Biol. 2001;237:324-32 pubmed
    ..Wnt7b also is required for normal organization of cells in the chorionic plate. Thus, Wnt7b signaling is central to the early stages of placental development in mammals. ..
  47. Raffel G, Chu G, Jesneck J, Cullen D, Bronson R, Bernard O, et al. Ott1 (Rbm15) is essential for placental vascular branching morphogenesis and embryonic development of the heart and spleen. Mol Cell Biol. 2009;29:333-41 pubmed publisher
    ..Thus, Ott1-dependent pathways, in addition to being implicated in leukemogenesis, may also be important for the pathogenesis of placental insufficiency and cardiac malformations. ..
  48. Luo J, Sladek R, Bader J, Matthyssen A, Rossant J, Giguere V. Placental abnormalities in mouse embryos lacking the orphan nuclear receptor ERR-beta. Nature. 1997;388:778-82 pubmed
    ..Our results indicate that ERR-beta has an important role in early placentation, and suggest that an inductive signal originating from or modified by the chorion is required for normal trophoblast proliferation and differentiation. ..
  49. Tian G, Singh U, Yu Y, Ellsworth B, Hemberger M, Geyer R, et al. Expression and function of the LIM homeobox containing genes Lhx3 and Lhx4 in the mouse placenta. Dev Dyn. 2008;237:1517-25 pubmed publisher
    ..However, absence of both LIM-3 genes did not interfere with placental transport nor consistently with expression of target genes such as Gnrhr. Thus, LHX3 and LHX4 appear to be dispensable for placental development and function. ..
  50. Zechner U, Reule M, Orth A, Bonhomme F, Strack B, Guénet -, et al. An X-chromosome linked locus contributes to abnormal placental development in mouse interspecific hybrid. Nat Genet. 1996;12:398-403 pubmed
    ..Hypotrophy of the placenta frequently leads to growth impairment or death of the fetus. One of the major genetic determinants of placental growth maps to the proximal part of the mouse X chromosome. ..
  51. Szabo R, Molinolo A, List K, Bugge T. Matriptase inhibition by hepatocyte growth factor activator inhibitor-1 is essential for placental development. Oncogene. 2007;26:1546-56 pubmed
    ..Furthermore, matriptase/HAI-1 double-deficient mice were phenotypically indistinguishable from matriptase single-deficient littermates. ..
  52. Rodriguez T, Sparrow D, Scott A, Withington S, Preis J, Michalicek J, et al. Cited1 is required in trophoblasts for placental development and for embryo growth and survival. Mol Cell Biol. 2004;24:228-44 pubmed
    ..We conclude that Cited1 is required in trophoblasts for normal placental development and subsequently for embryo viability. ..
  53. Tanaka M, Puchyr M, Gertsenstein M, Harpal K, Jaenisch R, Rossant J, et al. Parental origin-specific expression of Mash2 is established at the time of implantation with its imprinting mechanism highly resistant to genome-wide demethylation. Mech Dev. 1999;87:129-42 pubmed
    ..Our results suggest the possibility that a mechanism other than DNA methylation, such as allele-specific chromatin conformation, may be involved in maintenance of parental origin-specific expression of Mash2. ..