Alternative titles; symbols
HGNC Approved Gene Symbol: GCM1
Cytogenetic location: 6p12.1 Genomic coordinates (GRCh38) : 6:53,126,961-53,148,841 (from NCBI)
In the Drosophila nervous system, the 'glial cells missing' (gcm) gene is transiently expressed in glial precursors to switch their fate from the neuronal default to glia. Akiyama et al. (1996) demonstrated that the N-terminal region of gcm binds to DNA in a sequence-specific manner. Eleven gcm-binding sites are found in the 5-prime region of the 'repo' gene, whose expression is dependent on gcm.
By searching an EST database and by using RACE, Akiyama et al. (1996) identified cDNAs encoding GCMA, a human homolog of gcm. The predicted GCMA protein contains 436 amino acids. They also isolated cDNAs encoding 2 mouse gcm homologs, Gcma and Gcmb. The mammalian proteins share a conserved N-terminal region of approximately 150 amino acids that corresponds to the DNA-binding domain of gcm. The gcm motif of GCMA exhibited specific DNA-binding activity similar to that of gcm. Akiyama et al. (1996) concluded that the gcm motif defines a family of novel DNA-binding proteins, and may function in various aspects of cell fate determination.
Yamada et al. (2000) determined that the GCM1 gene contains 6 exons, spans about 22 kb, and is similar in overall organization to the mouse homolog. The gene contains several potential binding sites for transcriptions factors, including GATA-binding proteins, OCT1 (POU2F1; 164175), and basic helix-loop-helix proteins. The 5-prime flanking region includes a motif for GCM protein binding.
By FISH, Yamada et al. (2000) mapped the GCM1 gene to chromosome 6p.
Trophoblast cells of the placenta are established at the blastocyst stage and differentiate into specialized subtypes after implantation. In mammals, the placenta is the major, if not exclusive, site of GCM1 expression. Anson-Cartwright et al. (2000) showed that mouse 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. Mutation of Gcm1 in mice causes a complete block to branching of the chorioallantoic interface, resulting in embryonic mortality by embryonic day 10 due to absence of the placental labyrinth. In addition, chorionic trophoblast cells in Gcm1-deficient placentas do not fuse to form syncytiotrophoblast. Abnormal development of placental villi is frequently associated with fetal death and intrauterine growth restriction in humans.
Schreiber et al. (2000) reported a similar study indicating that mice lacking Gcm1 failed to form the labyrinthine layer and succumbed to placental insufficiency. Rinkenberger and Werb (2000) pointed out that fetal nutrition is dependent on the branching of a layer of placental trophoblast cells that sits between the maternal blood and fetal blood vessels. The discovery that expression of the transcription factor Gcm1 in trophoblast stem cells regulates branching of this specialized epithelium offered new insights into a process of pivotal importance to the function of the placenta.
Gunther et al. (2000) generated mice deficient in Gcm2 (603716) by targeted disruption. These mice had no parathyroid glands; however, they had normal parathyroid hormone levels. Expression and ablation studies identified the thymus, where Gcm1 is expressed, as an additional, downregulatable source of PTH.
Akiyama, Y., Hosoya, T., Poole, A. M., Hotta, Y. The gcm-motif: a novel DNA-binding motif conserved in Drosophila and mammals. Proc. Nat. Acad. Sci. 93: 14912-14916, 1996. [PubMed: 8962155] [Full Text: https://doi.org/10.1073/pnas.93.25.14912]
Anson-Cartwright, L., Dawson, K., Holmyard, D., Fisher, S. J., Lazzarini, R. A., Cross, J. C. The glial cells missing-1 protein is essential for branching morphogenesis in the chorioallantoic placenta. Nature Genet. 25: 311-314, 2000. [PubMed: 10888880] [Full Text: https://doi.org/10.1038/77076]
Gunther, T., Chen, Z.-F., Kim, J., Priemel, M., Rueger, J. M., Amling, M., Moseley, J. M., Martin, T. J., Anderson, D. J., Karsenty, G. Genetic ablation of parathyroid glands reveals another source of parathyroid hormone. Nature 406: 199-203, 2000. [PubMed: 10910362] [Full Text: https://doi.org/10.1038/35018111]
Rinkenberger, J., Werb, Z. The labyrinthine placenta. Nature Genet. 25: 248-250, 2000. [PubMed: 10888863] [Full Text: https://doi.org/10.1038/76985]
Schreiber, J., Riethmacher-Sonnenberg, E., Riethmacher, D., Tuerk, E. E., Enderich, J., Bosl, M. R., Wegner, M. Placental failure in mice lacking the mammalian homolog of glial cells missing, GCMa. Molec. Cell. Biol. 20: 2466-2474, 2000. [PubMed: 10713170] [Full Text: https://doi.org/10.1128/MCB.20.7.2466-2474.2000]
Yamada, K., Ogawa, H., Tamiya, G., Ikeno, M., Morita, M., Asakawa, S., Shimizu, N., Okazaki, T. Genomic organization, chromosomal localization, and the complete 22 kb DNA sequence of the human GCMa/GCM1, a placenta-specific transcription factor gene. Biochem. Biophys. Res. Commun. 278: 134-139, 2000. [PubMed: 11071865] [Full Text: https://doi.org/10.1006/bbrc.2000.3775]