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

• Northern blot and mRNA in situ hybridization studies showed that Gcm1 expression was readily detectable only in the placenta [14].

References