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Gene Review

Gcm1  -  glial cells missing homolog 1 (Drosophila)

Mus musculus

Synonyms: Chorion-specific transcription factor GCMa, GCM motif protein 1, GCMa, Gcm 1, Gcm a, ...
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Disease relevance of Gcm1

  • This effect was also observed by in utero injection of retrovirus harboring mouse Gcm1 into the embryonic brain [1].

High impact information on Gcm1

  • In addition, chorionic trophoblast cells in Gcm1-deficient placentas do not fuse to form syncytiotrophoblast [2].
  • We show here that Gcm1, encoding the transcription factor glial cells missing-1 (Gcm1), is expressed in small clusters of chorionic trophoblast cells at the flat chorionic plate stage and at sites of chorioallantoic folding and extension when morphogenesis begins [2].
  • Expression and ablation studies identified the thymus, where Gcm1, another Gcm homologue, is expressed, as the additional, downregulatable source of PTH [3].
  • The expression of several trophoblast markers was also altered, including an increase in the spongiotrophoblast marker Mash2 and decreases in the labyrinthine markers Tfeb and Gcm1 [4].
  • Genetic ablation of murine GCMa (mGCMa) is embryonic lethal, with mice dying between 9.5 and 10 days postcoitum [5].

Biological context of Gcm1

  • Moreover, the shaping of the maternal blood spaces within the labyrinth was dependent on chorioallantoic morphogenesis and therefore disrupted in Gcm1 mutants [6].
  • Our studies presented herein show that Gcm1 expression occurs in three distinct phases during placental development, each specific to a particular stage of chorio-allantois interaction [7].
  • Our results indicate that mGCMa plays a critical role in trophoblast differentiation and the signal transduction processes required for normal vascularization of the placenta [5].
  • Transactivation potential was present in two separate regions of mGCMa outside the DNA-binding domain [8].
  • Alanine scan mutagenesis of the DNA binding domain of mGCMa identified the three conserved amino acids K74, C76 and C125 as being essential for DNA binding [9].

Anatomical context of Gcm1

  • Ectopic expression of Gcm1 induces congenital spinal cord abnormalities [10].
  • However, cultures from mouse Gcm1-deficient mouse brains did not exhibit significant reductions in the number of astrocytes [1].
  • In agreement with the selective expression of mGCMa in labyrinthine trophoblasts, mutant placentas did not develop a functional labyrinth layer, which is necessary for nutrient and gas exchange between maternal and fetal blood [5].
  • While Gcm1 mRNA expression initiates independently within the chorion, the subsequent maintenance of mRNA expression as well as the onset of protein accumulation is dependent on contact with allantoic mesoderm [11].

Physical interactions of Gcm1

  • We show that Pitx proteins interact via their conserved homeodomain with the DNA-binding domain of GCMa [12].

Regulatory relationships of Gcm1

  • Furthermore, Pitx proteins influence GCMa-dependent promoter activation in a cell-specific manner [12].

Other interactions of Gcm1

  • Furthermore, pulse-chase experiments proved that the mGCMb protein has a half-life approximately four times shorter than mGCMa [13].
  • As a consequence, Pitx proteins and GCMa exhibit cooperative DNA binding [12].

Analytical, diagnostic and therapeutic context of Gcm1


  1. The potential to induce glial differentiation is conserved between Drosophila and mammalian glial cells missing genes. Iwasaki, Y., Hosoya, T., Takebayashi, H., Ogawa, Y., Hotta, Y., Ikenaka, K. Development (2003) [Pubmed]
  2. The glial cells missing-1 protein is essential for branching morphogenesis in the chorioallantoic placenta. Anson-Cartwright, L., Dawson, K., Holmyard, D., Fisher, S.J., Lazzarini, R.A., Cross, J.C. Nat. Genet. (2000) [Pubmed]
  3. Genetic ablation of parathyroid glands reveals another source of parathyroid hormone. Günther, T., Chen, Z.F., Kim, J., Priemel, M., Rueger, J.M., Amling, M., Moseley, J.M., Martin, T.J., Anderson, D.J., Karsenty, G. Nature (2000) [Pubmed]
  4. Placental but Not Heart Defects Are Associated with Elevated Hypoxia-Inducible Factor {alpha} Levels in Mice Lacking Prolyl Hydroxylase Domain Protein 2. Takeda, K., Ho, V.C., Takeda, H., Duan, L.J., Nagy, A., Fong, G.H. Mol. Cell. Biol. (2006) [Pubmed]
  5. Placental failure in mice lacking the mammalian homolog of glial cells missing, GCMa. Schreiber, J., Riethmacher-Sonnenberg, E., Riethmacher, D., Tuerk, E.E., Enderich, J., Bösl, M.R., Wegner, M. Mol. Cell. Biol. (2000) [Pubmed]
  6. Interactions between trophoblast cells and the maternal and fetal circulation in the mouse placenta. Adamson, S.L., Lu, Y., Whiteley, K.J., Holmyard, D., Hemberger, M., Pfarrer, C., Cross, J.C. Dev. Biol. (2002) [Pubmed]
  7. Gcm1 expression defines three stages of chorio-allantoic interaction during placental development. Stecca, B., Nait-Oumesmar, B., Kelley, K.A., Voss, A.K., Thomas, T., Lazzarini, R.A. Mech. Dev. (2002) [Pubmed]
  8. mGCMa is a murine transcription factor that overrides cell fate decisions in Drosophila. Reifegerste, R., Schreiber, J., Gülland, S., Lüdemann, A., Wegner, M. Mech. Dev. (1999) [Pubmed]
  9. Structural requirements for DNA binding of GCM proteins. Schreiber, J., Enderich, J., Wegner, M. Nucleic Acids Res. (1998) [Pubmed]
  10. Ectopic expression of Gcm1 induces congenital spinal cord abnormalities. Nait-Oumesmar, B., Stecca, B., Fatterpekar, G., Naidich, T., Corbin, J., Lazzarini, R.A. Development (2002) [Pubmed]
  11. Complex patterns of GCM1 mRNA and protein in villous and extravillous trophoblast cells of the human placenta. Baczyk, D., Satkunaratnam, A., Nait-Oumesmar, B., Huppertz, B., Cross, J.C., Kingdom, J.C. Placenta (2004) [Pubmed]
  12. Interaction, cooperative promoter modulation, and renal colocalization of GCMa and Pitx2. Schubert, S.W., Kardash, E., Khan, M.A., Cheusova, T., Kilian, K., Wegner, M., Hashemolhosseini, S. J. Biol. Chem. (2004) [Pubmed]
  13. Protein stability and domain topology determine the transcriptional activity of the mammalian glial cells missing homolog, GCMb. Tuerk, E.E., Schreiber, J., Wegner, M. J. Biol. Chem. (2000) [Pubmed]
  14. Murine Gcm1 gene is expressed in a subset of placental trophoblast cells. Basyuk, E., Cross, J.C., Corbin, J., Nakayama, H., Hunter, P., Nait-Oumesmar, B., Lazzarini, R.A. Dev. Dyn. (1999) [Pubmed]
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