Gene Symbol: Gcm2
Description: glial cells missing homolog 2
Alias: Gcm-rs1, Gcm1, Gcm1-rs2, chorion-specific transcription factor GCMb, GCM motif protein 2, mGCMb
Species: mouse
Products:     Gcm2

Top Publications

  1. Zou D, Silvius D, Davenport J, Grifone R, Maire P, Xu P. Patterning of the third pharyngeal pouch into thymus/parathyroid by Six and Eya1. Dev Biol. 2006;293:499-512 pubmed
    ..cells of the thymus/parathyroid rudiments fail to maintain the expression of the parathyroid-specific gene Gcm2 and the thymus-specific gene Foxn1 and subsequently undergo abnormal apoptosis, leading to a complete disappearance ..
  2. Corbeaux T, Hess I, Swann J, Kanzler B, Haas Assenbaum A, Boehm T. Thymopoiesis in mice depends on a Foxn1-positive thymic epithelial cell lineage. Proc Natl Acad Sci U S A. 2010;107:16613-8 pubmed publisher
    ..Our findings therefore support the notion that Foxn1 is the essential transcription factor regulating the differentiation of TECs and that its expression marks the major functional lineage of TECs in embryonic and adult thymic tissue...
  3. Gordon J, Bennett A, Blackburn C, Manley N. Gcm2 and Foxn1 mark early parathyroid- and thymus-specific domains in the developing third pharyngeal pouch. Mech Dev. 2001;103:141-3 pubmed
    ..The molecular mechanism that specifies this primordium into distinct organ domains is not known. The Gcm2 and Foxn1 transcription factors are required for development of the parathyroid and thymus respectively, and are ..
  4. Su D, Ellis S, Napier A, Lee K, Manley N. Hoxa3 and pax1 regulate epithelial cell death and proliferation during thymus and parathyroid organogenesis. Dev Biol. 2001;236:316-29 pubmed
    ..third pouch in Hoxa3(+/-)Pax1(-/-) compound mutants initiates normal expression of the parathyroid-specific Gcm2 and thymus-specific Foxn1 genes. However, Gcm2 expression is reduced at E11...
  5. Xu P, Zheng W, Laclef C, Maire P, Maas R, Peters H, et al. Eya1 is required for the morphogenesis of mammalian thymus, parathyroid and thyroid. Development. 2002;129:3033-44 pubmed
    ..In addition, we show that in Eya1(-/-) embryos, the expression of Gcm2 in the 3rd pouch endoderm is undetectable at E10...
  6. Zamisch M, Moore Scott B, Su D, Lucas P, Manley N, Richie E. Ontogeny and regulation of IL-7-expressing thymic epithelial cells. J Immunol. 2005;174:60-7 pubmed
  7. Tu Q, Pi M, Karsenty G, Simpson L, Liu S, Quarles L. Rescue of the skeletal phenotype in CasR-deficient mice by transfer onto the Gcm2 null background. J Clin Invest. 2003;111:1029-37 pubmed
    ..CasR deficiency was transferred onto the glial cells missing 2-deficient (Gcm2-deficient) background by intercrossing CasR- and Gcm2-deficient mice...
  8. Manley N, Selleri L, Brendolan A, Gordon J, Cleary M. Abnormalities of caudal pharyngeal pouch development in Pbx1 knockout mice mimic loss of Hox3 paralogs. Dev Biol. 2004;276:301-12 pubmed
    ..However, some aspects of the Pbx1 mutant phenotype included specific defects that were less severe than those found in known Hox mutant mice, suggesting that some functions of Hox proteins in this region are Pbx1-independent...
  9. Liu Z, Yu S, Manley N. Gcm2 is required for the differentiation and survival of parathyroid precursor cells in the parathyroid/thymus primordia. Dev Biol. 2007;305:333-46 pubmed
    ..5. Gcm2, a mouse ortholog of the Drosophila Glial Cells Missing gene, is expressed in the parathyroid-specific domains in ..

More Information


  1. Simmonds C, Karsenty G, Karaplis A, Kovacs C. Parathyroid hormone regulates fetal-placental mineral homeostasis. J Bone Miner Res. 2010;25:594-605 pubmed publisher
    ..Pth null mice have enlarged parathyroids that are incapable of making PTH, whereas Gcm2 null mice lack parathyroids but have PTH that arises from the thymus...
  2. Grigorieva I, Mirczuk S, Gaynor K, Nesbit M, Grigorieva E, Wei Q, et al. Gata3-deficient mice develop parathyroid abnormalities due to dysregulation of the parathyroid-specific transcription factor Gcm2. J Clin Invest. 2010;120:2144-55 pubmed publisher
    ..parathyroid-thymus primordia with fewer cells expressing the parathyroid-specific gene glial cells missing 2 (Gcm2), the homolog of human GCMB. In contrast, E11.5 Gata3-/- embryos had no Gcm2 expression and by E12...
  3. Gunther T, Chen Z, Kim J, Priemel M, Rueger J, Amling M, et al. Genetic ablation of parathyroid glands reveals another source of parathyroid hormone. Nature. 2000;406:199-203 pubmed
    ..Expression and ablation studies identified the thymus, where Gcm1, another Gcm homologue, is expressed, as the additional, downregulatable source of PTH...
  4. Kanemura Y, Hiraga S, Arita N, Ohnishi T, Izumoto S, Mori K, et al. Isolation and expression analysis of a novel human homologue of the Drosophila glial cells missing (gcm) gene. FEBS Lett. 1999;442:151-6 pubmed
    ..Our data suggest that humans have two homologues of gcm like mice and that human gcm genes form a novel family which may function not only during fetal development but also in the postnatal or pathological stage. ..
  5. Grevellec A, Graham A, Tucker A. Shh signalling restricts the expression of Gcm2 and controls the position of the developing parathyroids. Dev Biol. 2011;353:194-205 pubmed publisher
    ..pouches, and show that Hh signalling may be involved in restricting the expression of the parathyroid marker Gcm2 in the pharyngeal epithelium...
  6. Ivins S, Lammerts van Beuren K, Roberts C, James C, Lindsay E, Baldini A, et al. Microarray analysis detects differentially expressed genes in the pharyngeal region of mice lacking Tbx1. Dev Biol. 2005;285:554-69 pubmed
    ..Real-time quantitative PCR and in situ hybridization validated diminished expression of Pax9 and Gcm2, genes known to be required for normal thymus and parathyroid gland morphogenesis, whereas Pax1, Hoxa3, Eya1, and ..
  7. Okubo T, Kawamura A, Takahashi J, Yagi H, Morishima M, Matsuoka R, et al. Ripply3, a Tbx1 repressor, is required for development of the pharyngeal apparatus and its derivatives in mice. Development. 2011;138:339-48 pubmed publisher
    ..Together, our results show that Ripply3 plays a role in pharyngeal development, probably by regulating Tbx1 activity. ..
  8. Li Y, Kong J, Wei M, Chen Z, Liu S, Cao L. 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest. 2002;110:229-38 pubmed
    ..Its apparent critical role in electrolytes, volume, and blood pressure homeostasis suggests that vitamin D analogues could help prevent or ameliorate hypertension. ..
  9. Takahashi K, Ishida M, Hirokawa K, Takahashi H. Expression of the semaphorins Sema 3D and Sema 3F in the developing parathyroid and thymus. Dev Dyn. 2008;237:1699-708 pubmed publisher
    ..The expression of Sema 3D and Sema 3F was compared with that of gcm2, Pax1, and Neuropilin-1 and -2, and genes encoding a variety of Plexins by in situ hybridization during mouse ..
  10. Griffith A, Cardenas K, Carter C, Gordon J, Iberg A, Engleka K, et al. Increased thymus- and decreased parathyroid-fated organ domains in Splotch mutant embryos. Dev Biol. 2009;327:216-27 pubmed publisher
    ..Analyses of Foxn1 and Gcm2 expression revealed a dorsal shift in the border between parathyroid- and thymus-fated domains at E11...
  11. Guris D, Duester G, Papaioannou V, Imamoto A. Dose-dependent interaction of Tbx1 and Crkl and locally aberrant RA signaling in a model of del22q11 syndrome. Dev Cell. 2006;10:81-92 pubmed
    ..Thus, we suggest that del22q11 is a contiguous gene syndrome involving dose-sensitive interaction of CRKL and TBX1 and locally aberrant RA signaling. ..
  12. 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
    ..1996; this communication). Here we report the molecular organization of the murine Gcm1, its spatio-temporal pattern of expression in developing placenta, and its map position at E1-E3 on murine ..
  13. Hitoshi S, Ishino Y, Kumar A, Jasmine S, Tanaka K, Kondo T, et al. Mammalian Gcm genes induce Hes5 expression by active DNA demethylation and induce neural stem cells. Nat Neurosci. 2011;14:957-64 pubmed publisher
    ..We found that mammalian Gcm1 and Gcm2 (glial cells missing 1 and 2) are involved in the epigenetic regulation of Hes5 transcription by DNA demethylation ..
  14. Kim J, Jones B, Zock C, Chen Z, Wang H, Goodman C, et al. Isolation and characterization of mammalian homologs of the Drosophila gene glial cells missing. Proc Natl Acad Sci U S A. 1998;95:12364-9 pubmed
    ..We report here the isolation of two mammalian gcm homologs, Gcm1 and Gcm2, and the characterization of their expression patterns during embryonic development...
  15. Gordon J, Manley N. Mechanisms of thymus organogenesis and morphogenesis. Development. 2011;138:3865-78 pubmed publisher
    ..These studies are making significant progress in identifying the molecular and cellular mechanisms that control specification, early organogenesis and morphogenesis of the thymus. ..
  16. Yuan Z, Opas E, Vrikshajanani C, Libutti S, Levine M. Generation of mice encoding a conditional null allele of Gcm2. Transgenic Res. 2014;23:631-41 pubmed publisher
    Glial cells missing homolog 2 (GCM2) is a transcription factor that is expressed predominately in the pharyngeal pouches and, at later stages, in the developing and mature parathyroid glands...
  17. Kamitani Kawamoto A, Hamada M, Moriguchi T, Miyai M, Saji F, Hatamura I, et al. MafB interacts with Gcm2 and regulates parathyroid hormone expression and parathyroid development. J Bone Miner Res. 2011;26:2463-72 pubmed publisher
    ..In mice, the expression of transcription factor Glial cell missing 2 (Gcm2) begins in the dorsal/anterior part of the primordium on embryonic day 9.5 (E9...
  18. Bowl M, Mirczuk S, Grigorieva I, Piret S, Cranston T, Southam L, et al. Identification and characterization of novel parathyroid-specific transcription factor Glial Cells Missing Homolog B (GCMB) mutations in eight families with autosomal recessive hypoparathyroidism. Hum Mol Genet. 2010;19:2028-38 pubmed publisher
  19. David V, Dai B, Martin A, Huang J, Han X, Quarles L. Calcium regulates FGF-23 expression in bone. Endocrinology. 2013;154:4469-82 pubmed publisher
    ..FGF-23 expression under basal conditions and in response to PTH, doxercalciferol, or high-calcium diet treatment in Gcm2(-/-) and Cyp27b1(-/-) mutant mice...
  20. Raisz L. The hunting of the snark: the elusive calcium receptor(s). J Clin Invest. 2003;111:945-7 pubmed
  21. Cohen S, Moulin M, Schilling O, Meyer Klaucke W, Schreiber J, Wegner M, et al. The GCM domain is a Zn-coordinating DNA-binding domain. FEBS Lett. 2002;528:95-100 pubmed
    ..Our results define the GCM domain as a new type of Zn-coordinating, sequence-specific DNA-binding domain. ..
  22. Reeh K, Cardenas K, Bain V, Liu Z, LAURENT M, Manley N, et al. Ectopic TBX1 suppresses thymic epithelial cell differentiation and proliferation during thymus organogenesis. Development. 2014;141:2950-8 pubmed publisher
    ..By contrast, ectopic Tbx1 did not alter the expression pattern of Gcm2, a transcription factor restricted to the parathyroid-fated domain and required for parathyroid development...
  23. Huh S, Ornitz D. Beta-catenin deficiency causes DiGeorge syndrome-like phenotypes through regulation of Tbx1. Development. 2010;137:1137-47 pubmed publisher
    ..These findings identify Wnt-beta-catenin signaling as a crucial upstream regulator of a Tbx1-Fgf8 signaling pathway and suggest that factors that affect Wnt-beta-catenin signaling could modify the incidence and severity of DGS...
  24. Patel S, Gordon J, Mahbub F, Blackburn C, Manley N. Bmp4 and Noggin expression during early thymus and parathyroid organogenesis. Gene Expr Patterns. 2006;6:794-9 pubmed
    ..parathyroid-specific organ domains are established within the primordium prior to formation of the organs proper: Gcm2 expression defines the prospective parathyroid cells in the dorsal pouch from E9...
  25. Moore Scott B, Manley N. Differential expression of Sonic hedgehog along the anterior-posterior axis regulates patterning of pharyngeal pouch endoderm and pharyngeal endoderm-derived organs. Dev Biol. 2005;278:323-35 pubmed
    ..Changes in the distribution of Bmp4 and Gcm2 in the third pouch endoderm and subsequent organ phenotypes in Shh-/- mutants suggested that exclusion of Shh from ..
  26. Liu Z, Farley A, Chen L, Kirby B, Kovacs C, Blackburn C, et al. Thymus-associated parathyroid hormone has two cellular origins with distinct endocrine and immunological functions. PLoS Genet. 2010;6:e1001251 pubmed publisher
    ..proposed to provide an auxiliary source of PTH, resulting in a higher than expected survival rate for aparathyroid Gcm2?/? mutants...
  27. Liu S, Tang W, Zhou J, Stubbs J, Luo Q, Pi M, et al. Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D. J Am Soc Nephrol. 2006;17:1305-15 pubmed
    ..In Gcm2 null mice, low 1,25(OH)(2)D(3) levels were associated with a three-fold reduction in FGF23 levels that were ..
  28. Chen L, Zhao P, Wells L, Amemiya C, Condie B, Manley N. Mouse and zebrafish Hoxa3 orthologues have nonequivalent in vivo protein function. Proc Natl Acad Sci U S A. 2010;107:10555-60 pubmed publisher
    ..The inability of zfhoxa3a to perform all of the normal roles of mouse Hoxa3 illustrates that Hox orthologues are not always functionally interchangeable. ..
  29. Iwasaki Y, Hosoya T, Takebayashi H, Ogawa Y, Hotta Y, Ikenaka K. The potential to induce glial differentiation is conserved between Drosophila and mammalian glial cells missing genes. Development. 2003;130:6027-35 pubmed
    ..Expression of these genes appeared to influence fibroblast features. In particular, mouse Gcm1 induced the expression of astrocyte-specific Ca(2+)-binding protein, S100beta, in those cells...
  30. Hunter P, Swanson B, Haendel M, Lyons G, Cross J. Mrj encodes a DnaJ-related co-chaperone that is essential for murine placental development. Development. 1999;126:1247-58 pubmed
    ..However, expression of the chorionic trophoblast-specific transcription factor genes Err2 and Gcm1 was significantly reduced...
  31. Wei Q, Condie B. A focused in situ hybridization screen identifies candidate transcriptional regulators of thymic epithelial cell development and function. PLoS ONE. 2011;6:e26795 pubmed publisher
    ..Our results also demonstrate heterogeneity of TECs marked by the differential expression of transcription factors, potentially providing new insights into the regulation of TEC differentiation. ..
  32. Chojnowski J, Masuda K, Trau H, Thomas K, Capecchi M, Manley N. Multiple roles for HOXA3 in regulating thymus and parathyroid differentiation and morphogenesis in mouse. Development. 2014;141:3697-708 pubmed publisher
    ..Expression of the parathyroid marker Gcm2 was initiated but was quickly downregulated and differentiation failed; by contrast, thymus markers were delayed ..
  33. Bain V, Gordon J, O Neil J, Ramos I, Richie E, Manley N. Tissue-specific roles for sonic hedgehog signaling in establishing thymus and parathyroid organ fate. Development. 2016;143:4027-4037 pubmed
    ..However, ectopic SHH signaling was insufficient to expand the GCM2-positive parathyroid domain, indicating that multiple inputs, some of which might be independent of SHH signaling, ..
  34. Akiyama Y, Hosoya T, Poole A, Hotta Y. The gcm-motif: a novel DNA-binding motif conserved in Drosophila and mammals. Proc Natl Acad Sci U S A. 1996;93:14912-6 pubmed
    ..The gcm-motif, therefore, forms a family of novel DNA-binding proteins, and may function in various aspects of cell fate determination. ..
  35. Gardiner J, Jackson A, Gordon J, Lickert H, Manley N, Basson M. Localised inhibition of FGF signalling in the third pharyngeal pouch is required for normal thymus and parathyroid organogenesis. Development. 2012;139:3456-66 pubmed publisher
  36. Foster K, Gordon J, Cardenas K, Veiga Fernandes H, Makinen T, Grigorieva E, et al. EphB-ephrin-B2 interactions are required for thymus migration during organogenesis. Proc Natl Acad Sci U S A. 2010;107:13414-9 pubmed publisher
    ..This implies a NC-derived cell-specific role of EphB-ephrin-B2 interactions in the collective migration of the thymic rudiment during organogenesis. ..
  37. Geibel J, Sritharan K, Geibel R, Geibel P, Persing J, Seeger A, et al. Calcium-sensing receptor abrogates secretagogue- induced increases in intestinal net fluid secretion by enhancing cyclic nucleotide destruction. Proc Natl Acad Sci U S A. 2006;103:9390-7 pubmed
    ..The reversal of cholera toxin- and STa endotoxin-induced fluid secretion by a small-molecule CaSR agonist suggests that these compounds may provide a unique therapy for secretory diarrheas. ..
  38. Liu C, Saito F, Liu Z, Lei Y, Uehara S, Love P, et al. Coordination between CCR7- and CCR9-mediated chemokine signals in prevascular fetal thymus colonization. Blood. 2006;108:2531-9 pubmed
    ..Unexpectedly, CCL21, a CCR7 ligand, was expressed not by Foxn1-dependent thymic primordium but by Gcm2-dependent parathyroid primordium, whereas CCL25, a CCR9 ligand, was predominantly expressed by Foxn1-dependent ..
  39. Altshuller Y, Copeland N, Gilbert D, Jenkins N, Frohman M. Gcm1, a mammalian homolog of Drosophila glial cells missing. FEBS Lett. 1996;393:201-4 pubmed
    ..Mouse Gcm1 demonstrates extensive similarity to Drosophila gcm but is expressed at very low levels during neuro- and ..