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Gene Review

Esx1  -  extraembryonic, spermatogenesis, homeobox 1

Mus musculus

Synonyms: Spx1
 
 
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Disease relevance of Esx1

 

High impact information on Esx1

  • Esx1 is an X-chromosome-imprinted regulator of placental development and fetal growth [1].
  • Although Esx1 mutant embryos were initially comparable in size with controls at 13.5 days post coitum (dpc), their placentas were significantly larger [1].
  • Heterozygous females that inherited the Esx1 mutation from their mother, however, were born 20% smaller than normal and are identical in phenotype to hemizygous mutant males and homozygous mutant females [1].
  • We show here that the X-linked homeobox gene Esx1 (refs 5,6), whose expression is restricted to extraembryonic tissues, is a chromosomally imprinted regulator of placental morphogenesis and trophoblast differentiation [1].
  • However, by day 10.5 of development, expression of the paired-like homeodomain gene Esx1 was strongly down-regulated in affected placenta tissue, suggesting that Dlx3 is required for the maintenance of Esx1 expression, normal placental morphogenesis, and embryonic survival [4].
 

Biological context of Esx1

  • Finally, genetic mapping experiments place mouse Dach2 on the X chromosome between Xist and Esx1 [5].
  • The Esx1 homeobox gene is of particular interest because it is among the few regulatory genes that have specific expression and function in the placenta during murine development [6].
  • Using the Esx1 gene promoter as a model for a Dlx3-responsive gene, studies demonstrate two near consensus Dlx3 binding sites within the proximal 2.3 kb of the transcription start site [7].
  • A novel paired-like homeobox gene, designated Esx1, was isolated in a screen for homeobox genes that regulate mouse embryogenesis [8].
  • In a previous study, we carried out comparative gene expression analysis in three models of placental hyperplasias, cloning, interspecies hybridization (IHPD), and Esx1 deletion [9].
 

Anatomical context of Esx1

  • Thus, the identification of Esx1 provides a molecular entry point into a genetic pathway to understand X chromosome-regulated fetal-maternal interactions and male germ cell development [8].
  • In adult tissues, Esx1 expression was detected only in testes [8].
  • During embryogenesis, Esx1 expression was restricted to extraembryonic tissues, including the endoderm of the visceral yolk sac, the ectoderm of the chorion, and subsequently the labyrinthine trophoblast of the chorioallantoic placenta [8].
 

Other interactions of Esx1

 

Analytical, diagnostic and therapeutic context of Esx1

References

  1. Esx1 is an X-chromosome-imprinted regulator of placental development and fetal growth. Li, Y., Behringer, R.R. Nat. Genet. (1998) [Pubmed]
  2. Proliferation and growth factor expression in abnormally enlarged placentas of mouse interspecific hybrids. Zechner, U., Hemberger, M., Constância, M., Orth, A., Dragatsis, I., Lüttges, A., Hameister, H., Fundele, R. Dev. Dyn. (2002) [Pubmed]
  3. Biparental expression of ESX1L gene in placentas from normal and intrauterine growth-restricted pregnancies. Grati, F.R., Sirchia, S.M., Gentilin, B., Rossella, F., Ramoscelli, L., Antonazzo, P., Cavallari, U., Bulfamante, G., Cetin, I., Simoni, G., Miozzo, M. Eur. J. Hum. Genet. (2004) [Pubmed]
  4. Placental failure in mice lacking the homeobox gene Dlx3. Morasso, M.I., Grinberg, A., Robinson, G., Sargent, T.D., Mahon, K.A. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  5. Characterization of mouse Dach2, a homologue of Drosophila dachshund. Davis, R.J., Shen, W., Sandler, Y.I., Heanue, T.A., Mardon, G. Mech. Dev. (2001) [Pubmed]
  6. A novel PF/PN motif inhibits nuclear localization and DNA binding activity of the ESX1 homeoprotein. Yan, Y.T., Stein, S.M., Ding, J., Shen, M.M., Abate-Shen, C. Mol. Cell. Biol. (2000) [Pubmed]
  7. Smad6 represses Dlx3 transcriptional activity through inhibition of DNA binding. Berghorn, K.A., Clark-Campbell, P.A., Han, L., McGrattan, M., Weiss, R.S., Roberson, M.S. J. Biol. Chem. (2006) [Pubmed]
  8. Esx1, a novel X chromosome-linked homeobox gene expressed in mouse extraembryonic tissues and male germ cells. Li, Y., Lemaire, P., Behringer, R.R. Dev. Biol. (1997) [Pubmed]
  9. Expression and functional analysis of genes deregulated in mouse placental overgrowth models: Car2 and Ncam1. Singh, U., Sun, T., Shi, W., Schulz, R., Nuber, U.A., Varanou, A., Hemberger, M.C., Elliott, R.W., Ohta, H., Wakayama, T., Fundele, R. Dev. Dyn. (2005) [Pubmed]
 
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