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Gene Review

Ysg1  -  yolk sac gene 1

Mus musculus

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Disease relevance of Ysg1


Psychiatry related information on Ysg1

  • The deficiency of MHC antigens in the apical membrane may account for the failure of sensitized females to reject the yolk sac, whereas the composition of the laterobasal membrane is probably less important to maternal-fetal relations [5].
  • TGFbeta inhibition of yolk-sac-like differentiation of human embryonic stem-cell-derived embryoid bodies illustrates differences between early mouse and human development [6].

High impact information on Ysg1

  • HoxB4 confers definitive lymphoid-myeloid engraftment potential on embryonic stem cell and yolk sac hematopoietic progenitors [7].
  • In an effort to characterize factors that distinguish the definitive adult hematopoietic stem cell (HSC) and primitive progenitors derived from yolk sac or embryonic stem (ES) cells, we examined the effect of ectopic expression of HoxB4, a homeotic selector gene implicated in self-renewal of definitive HSCs [7].
  • Map3k3-/- embryos died at approximately embryonic day (E) 11, displaying disruption of blood vessel development and the structural integrity of the yolk sac [8].
  • Embryos homozygous for the Hand1 null allele died between embryonic days 8.5 and 9.5 and exhibited yolk sac abnormalities due to a deficiency in extraembryonic mesoderm [9].
  • We also demonstrate that cells lacking Flk1 are unable to reach the correct location to form blood islands, suggesting that Flk1 is involved in the movement of cells from the posterior primitive streak to the yolk sac and, possibly, to the intraembryonic sites of early hematopoiesis [10].

Chemical compound and disease context of Ysg1


Biological context of Ysg1

  • Two sites of hematopoietic activity, the yolk sac and aorta-gonad-mesonephros (AGM) region, function in mouse ontogeny at the pre-liver stage of hematopoiesis [16].
  • Phenotyping of mRNA demonstrated exclusive expression from the paternal allele in all embryonic tissues, including visceral yolk sac, between 11 and 12.5 days of gestation [17].
  • Analysis indicated that embryonic erythropoiesis, which occurs in the yolk sac, was not impaired by the c-myb alteration [18].
  • If it is correct that the visceral endoderm of the early embryo makes a major contribution to the formation of the endoderm portion of the visceral yolk sac, then it is clear that a switch in collagen gene expression must occur as it does so [19].
  • Preferential expression of the maternally derived X chromosome in the mouse yolk sac [20].

Anatomical context of Ysg1

  • Little or no type IV collagen synthesis was detected in the endoderm of the visceral yolk sac [19].
  • The endoderm of the visceral yolk sac was shown to be synthesizing primarily type I collagen, while the mesoderm layer of this membrane synthesized both type I and IV collagens [19].
  • The endodermal portion of the visceral yolk sac did not react, while small amounts were found in the amnion [19].
  • Two types of tissues have been examined with respect to randomness of inactivation in 14-day mouse conceptuses: 1) fetal tissue, which undergoes random inactivation of either the maternal or paternal X; and 2) yolk sac endoderm tissue, an extraembryonic membrane, which normally undergoes nonrandom inactivation of the paternal X [21].
  • It is widely accepted that during murine embryogenesis, totipotent haematopoietic stem cells first originate in the yolk sac, then migrate to the fetal liver and finally colonize the bone marrow shortly before birth [22].

Associations of Ysg1 with chemical compounds

  • Administration of AGM-1470 to pregnant mice resulted in complete failure of embryonic growth due to interference with decidualization, placental and yolk sac formation, and embryonic vascular development [23].
  • In addition, the 89-kd and 59-kd HSP are not stimulated by an arsenite shock in contrast to what is observed with fibroblasts or cells of the parietal yolk sac type [24].
  • Presomitic and 3- to 12-somite pair cultured mouse embryos were deprived of retinoic acid (RA) by yolk-sac injections of antisense oligodeoxynucleotides for retinol binding protein (RBP) [25].
  • Developmental abnormalities in cultured mouse embryos deprived of retinoic by inhibition of yolk-sac retinol binding protein synthesis [25].
  • Embryos stain weakly with benzidine reagent, and yolk sac cells express globin RNAs, indicating globin gene activation in the absence of GATA-1 [26].

Physical interactions of Ysg1


Regulatory relationships of Ysg1

  • In mouse, Gatm is expressed during development and is imprinted in the placenta and yolk sac, but not in embryonic tissues [29].
  • Thus, under certain growth factor conditions, Tpo directly inhibits early yolk sac erythroid CFU growth but facilitates megakaryocyte and mixed lineage colony formation [30].
  • Flow-cytometric analysis showed that hemopoiesis in the yolk sac and fetal liver started from cells that express c-Kit [31].
  • Fzd5 mRNA was expressed in the yolk sac, eye and lung bud at 9.5 days post coitum [32].
  • In the developing embryo, Vezf1 is expressed in the yolk sac mesoderm and the endothelium of the developing vasculature and, in addition, in mesodermal and neuronal tissues [33].

Other interactions of Ysg1

  • A modest decline in Ins-2 RNA was observed in the yolk sac [34].
  • During early development of the mouse embryo, expression of the metallothionein-I (MT-I) gene is heightened specifically in the endoderm cells of the visceral yolk sac [35].
  • PECAM staining of yolk sac endothelial cells showed the absence of branching arteries and veins, the absence of a capillary bed, and the presence of large avascular spaces between the blood vessels [36].
  • Expression of Ipl is highest in placenta and yolk sac, where its mRNA is derived almost entirely from the maternal allele [37].
  • Here, we show that deletion of the C-terminal half of Bruce, including the UBC domain, causes activation of caspases and apoptosis in the placenta and yolk sac, leading to embryonic lethality [38].

Analytical, diagnostic and therapeutic context of Ysg1

  • We report the molecular cloning of two groups of genes expressed in the yolk sac: a group of genes expressed in the day-8.5 yolk sac at higher levels than in the day-8.5 embryo proper and up-regulated during EB development, and another group of day-8.5 yolk sac genes not expressed in the day-8.5 embryo proper or in EBs [39].
  • We report here that approximately half of homozygous embryos deficient in factor V (Fv-/-), which have been generated by gene targeting, die at embryonic day (E) 9-10, possibly as a result of an abnormality in the yolk-sac vasculature [40].
  • Here, we separated yolk sac and intraembryonic splanchnopleura prior to circulation and maintained the explants in organ culture before transfer [41].
  • In addition, we show by in situ hybridization to tissue sections that all endoderm cells of the visceral yolk sac contain AFP mRNA, indicating that the visceral endoderm layer is a homogeneous population of cells with respect to transcription of the AFP gene [42].
  • We show here that cell suspensions from day 7 early-mid-primitive streak stage embryo proper generated early immature PgP-1+ Joro 177+ Lin- hematopoietic cells and some Mac-1+ myeloid and TER 119+ erythroid cells after co-culture with the yolk sac-derived stromal cell line YS6 without addition of exogenous cytokines [43].


  1. Histologic analyses of experimental tumors from mouse blastocyst-derived cell lines. Sherman, M.I., Miller, R.A., Richter, C.B. J. Natl. Cancer Inst. (1977) [Pubmed]
  2. Yolk sac carcinoma grown from rat egg cylinders. Damjanov, I., Sell, S. J. Natl. Cancer Inst. (1977) [Pubmed]
  3. Pure yolk sac carcinoma of the mouse uterus: report of 8 cases. Stewart, H.L., Sass, B., Deringer, M.K., Dunn, T.B., Liotta, L.A., Togo, S. J. Natl. Cancer Inst. (1984) [Pubmed]
  4. beta-Adrenergic receptors in pediatric tumors: uncoupled beta 1-adrenergic receptor in Ewing's sarcoma. Whitsett, J.A., Burdsall, J., Workman, L., Hollinger, B., Neely, J. J. Natl. Cancer Inst. (1983) [Pubmed]
  5. Epithelium of mouse yolk sac placenta lacks H-2 complex alloantigens. Parr, E.L., Blanden, R.V., Tulsi, R.S. J. Exp. Med. (1980) [Pubmed]
  6. TGFbeta inhibition of yolk-sac-like differentiation of human embryonic stem-cell-derived embryoid bodies illustrates differences between early mouse and human development. Poon, E., Clermont, F., Firpo, M.T., Akhurst, R.J. J. Cell. Sci. (2006) [Pubmed]
  7. HoxB4 confers definitive lymphoid-myeloid engraftment potential on embryonic stem cell and yolk sac hematopoietic progenitors. Kyba, M., Perlingeiro, R.C., Daley, G.Q. Cell (2002) [Pubmed]
  8. Mekk3 is essential for early embryonic cardiovascular development. Yang, J., Boerm, M., McCarty, M., Bucana, C., Fidler, I.J., Zhuang, Y., Su, B. Nat. Genet. (2000) [Pubmed]
  9. Heart and extra-embryonic mesodermal defects in mouse embryos lacking the bHLH transcription factor Hand1. Firulli, A.B., McFadden, D.G., Lin, Q., Srivastava, D., Olson, E.N. Nat. Genet. (1998) [Pubmed]
  10. A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis. Shalaby, F., Ho, J., Stanford, W.L., Fischer, K.D., Schuh, A.C., Schwartz, L., Bernstein, A., Rossant, J. Cell (1997) [Pubmed]
  11. Codistribution of heparan sulfate proteoglycan, laminin, and fibronectin in the extracellular matrix of normal rat kidney cells and their coordinate absence in transformed cells. Hayman, E.G., Oldberg, A., Martin, G.R., Ruoslahti, E. J. Cell Biol. (1982) [Pubmed]
  12. Expression of the murine apolipoprotein E gene is coupled to the differentiated state of F9 embryonal carcinoma cells. Basheeruddin, K., Stein, P., Strickland, S., Williams, D.L. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  13. Hyperglycemia-induced vasculopathy in the murine vitelline vasculature: correlation with PECAM-1/CD31 tyrosine phosphorylation state. Pinter, E., Mahooti, S., Wang, Y., Imhof, B.A., Madri, J.A. Am. J. Pathol. (1999) [Pubmed]
  14. Immunohistochemical localization of murine stage-specific embryonic antigens in human testicular germ cell tumors. Damjanov, I., Fox, N., Knowles, B.B., Solter, D., Lange, P.H., Fraley, E.E. Am. J. Pathol. (1982) [Pubmed]
  15. Immunological and biological characterization of Coxiella burnetii, phases I and II, separated from host components. Williams, J.C., Peacock, M.G., McCaul, T.F. Infect. Immun. (1981) [Pubmed]
  16. Definitive hematopoiesis is autonomously initiated by the AGM region. Medvinsky, A., Dzierzak, E. Cell (1996) [Pubmed]
  17. Parental imprinting of the Mas protooncogene in mouse. Villar, A.J., Pedersen, R.A. Nat. Genet. (1994) [Pubmed]
  18. A functional c-myb gene is required for normal murine fetal hepatic hematopoiesis. Mucenski, M.L., McLain, K., Kier, A.B., Swerdlow, S.H., Schreiner, C.M., Miller, T.A., Pietryga, D.W., Scott, W.J., Potter, S.S. Cell (1991) [Pubmed]
  19. The localization and synthesis of some collagen types in developing mouse embryos. Adamson, E.D., Ayers, S.E. Cell (1979) [Pubmed]
  20. Preferential expression of the maternally derived X chromosome in the mouse yolk sac. West, J.D., Frels, W.I., Chapman, V.M., Papaioannou, V.E. Cell (1977) [Pubmed]
  21. Differences in the DNA of the inactive X chromosomes of fetal and extraembryonic tissues of mice. Kratzer, P.G., Chapman, V.M., Lambert, H., Evans, R.E., Liskay, R.M. Cell (1983) [Pubmed]
  22. An early pre-liver intraembryonic source of CFU-S in the developing mouse. Medvinsky, A.L., Samoylina, N.L., Müller, A.M., Dzierzak, E.A. Nature (1993) [Pubmed]
  23. Critical components of the female reproductive pathway are suppressed by the angiogenesis inhibitor AGM-1470. Klauber, N., Rohan, R.M., Flynn, E., D'Amato, R.J. Nat. Med. (1997) [Pubmed]
  24. Spontaneous high expression of heat-shock proteins in mouse embryonal carcinoma cells and ectoderm from day 8 mouse embryo. Bensaude, O., Morange, M. EMBO J. (1983) [Pubmed]
  25. Developmental abnormalities in cultured mouse embryos deprived of retinoic by inhibition of yolk-sac retinol binding protein synthesis. Båvik, C., Ward, S.J., Chambon, P. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  26. Arrested development of embryonic red cell precursors in mouse embryos lacking transcription factor GATA-1. Fujiwara, Y., Browne, C.P., Cunniff, K., Goff, S.C., Orkin, S.H. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  27. Post-translational regulation of AP-1 transcription factor DNA-binding activity in the rat conceptus. Ozolins, T.R., Hales, B.F. Mol. Pharmacol. (1999) [Pubmed]
  28. Glucocorticoid receptors in murine visceral yolk sac and liver during development. Andrews, G.K. J. Steroid Biochem. (1985) [Pubmed]
  29. Gatm, a creatine synthesis enzyme, is imprinted in mouse placenta. Sandell, L.L., Guan, X.J., Ingram, R., Tilghman, S.M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  30. Thrombopoietin promotes mixed lineage and megakaryocytic colony-forming cell growth but inhibits primitive and definitive erythropoiesis in cells isolated from early murine yolk sacs. Xie, X., Chan, R.J., Johnson, S.A., Starr, M., McCarthy, J., Kapur, R., Yoder, M.C. Blood (2003) [Pubmed]
  31. Expression and function of c-Kit in fetal hemopoietic progenitor cells: transition from the early c-Kit-independent to the late c-Kit-dependent wave of hemopoiesis in the murine embryo. Ogawa, M., Nishikawa, S., Yoshinaga, K., Hayashi, S., Kunisada, T., Nakao, J., Kina, T., Sudo, T., Kodama, H., Nishikawa, S. Development (1993) [Pubmed]
  32. Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis. Ishikawa, T., Tamai, Y., Zorn, A.M., Yoshida, H., Seldin, M.F., Nishikawa, S., Taketo, M.M. Development (2001) [Pubmed]
  33. Dosage-dependent requirement for mouse Vezf1 in vascular system development. Kuhnert, F., Campagnolo, L., Xiong, J.W., Lemons, D., Fitch, M.J., Zou, Z., Kiosses, W.B., Gardner, H., Stuhlmann, H. Dev. Biol. (2005) [Pubmed]
  34. An enhancer deletion affects both H19 and Igf2 expression. Leighton, P.A., Saam, J.R., Ingram, R.S., Stewart, C.L., Tilghman, S.M. Genes Dev. (1995) [Pubmed]
  35. The transcription factors MTF-1 and USF1 cooperate to regulate mouse metallothionein-I expression in response to the essential metal zinc in visceral endoderm cells during early development. Andrews, G.K., Lee, D.K., Ravindra, R., Lichtlen, P., Sirito, M., Sawadogo, M., Schaffner, W. EMBO J. (2001) [Pubmed]
  36. Targeting of both mouse neuropilin-1 and neuropilin-2 genes severely impairs developmental yolk sac and embryonic angiogenesis. Takashima, S., Kitakaze, M., Asakura, M., Asanuma, H., Sanada, S., Tashiro, F., Niwa, H., Miyazaki Ji, J., Hirota, S., Kitamura, Y., Kitsukawa, T., Fujisawa, H., Klagsbrun, M., Hori, M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  37. Placental overgrowth in mice lacking the imprinted gene Ipl. Frank, D., Fortino, W., Clark, L., Musalo, R., Wang, W., Saxena, A., Li, C.M., Reik, W., Ludwig, T., Tycko, B. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  38. The Birc6 (Bruce) gene regulates p53 and the mitochondrial pathway of apoptosis and is essential for mouse embryonic development. Ren, J., Shi, M., Liu, R., Yang, Q.H., Johnson, T., Skarnes, W.C., Du, C. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  39. A new approach to the study of haematopoietic development in the yolk sac and embryoid bodies. Guimarães, M.J., Bazan, J.F., Zlotnik, A., Wiles, M.V., Grimaldi, J.C., Lee, F., McClanahan, T. Development (1995) [Pubmed]
  40. Fatal haemorrhage and incomplete block to embryogenesis in mice lacking coagulation factor V. Cui, J., O'Shea, K.S., Purkayastha, A., Saunders, T.L., Ginsburg, D. Nature (1996) [Pubmed]
  41. Intraembryonic, but not yolk sac hematopoietic precursors, isolated before circulation, provide long-term multilineage reconstitution. Cumano, A., Ferraz, J.C., Klaine, M., Di Santo, J.P., Godin, I. Immunity (2001) [Pubmed]
  42. Tissue specificity of alpha-fetoprotein messenger RNA expression during mouse embryogenesis. Dziadek, M.A., Andrews, G.K. EMBO J. (1983) [Pubmed]
  43. Primitive lymphohematopoietic precursor cell lines generated in culture from day 7 early-mid-primitive streak stage mouse embryo. Palacios, R., Imhof, B.A. EMBO J. (1996) [Pubmed]
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