Disease relevance of gcm

• Recent data point to an involvement of GCM proteins in different pathological contexts, such as preeclampsia, hyper- or hypoparathyroidism, and parathyroid gland tumors [1].
• After division, the medial daughter cell expressed GCM protein to produce three glial cells, while the lateral daughter cell with no GCM expression produced ganglion mother cells, secondary precursors of neurons [2].

High impact information on gcm

• We have identified a gene, glial cells missing (gcm), that encodes a novel nuclear protein expressed transiently in early glial cells [3].
• glial cells missing and gcm2 cell autonomously regulate both glial and neuronal development in the visual system of Drosophila [4].
• Our findings further suggest that gcm genes regulate neurogenesis through collaboration with the Hedgehog-signaling pathway [4].
• We show that the transcriptional regulator Dachshund acts downstream of gcm genes and is required to make lamina precursor cells and lamina neurons competent for neuronal differentiation through regulation of epidermal growth factor receptor levels [4].
• We demonstrate that Gcm and Gcm2 are expressed in both glial and neuronal precursors within the optic lobe [4].

Biological context of gcm

• Furthermore, we show that prohemocytes are bipotent progenitors, and that downregulation of gcm/gcm2 is required for lz-induced crystal cell formation [5].
• The transcription factors Glial cells missing (Gcm) and Gcm2 are known to play a crucial role in promoting glial-cell differentiation during Drosophila embryogenesis [4].
• By comparing the deduced amino acid sequences of these gene products, we were able to define the "gcm motif," an evolutionarily conserved motif with DNA-binding activity [6].
• In the dorsal bipolar dendritic (dbd) sensory lineage in the embryonic peripheral nervous system (PNS), asymmetric cell division of the dbd precursor produces a neuron and a glial cell, where gcm expression is activated in the glial daughter [7].
• Terminal tendon cell differentiation requires the glide/gcm complex [8].

Anatomical context of gcm

• Removal of gcm and gcm2 function shows that the two genes act redundantly and are required for the formation of a subset of glial cells [4].
• Resolving embryonic blood cell fate choice in Drosophila: interplay of GCM and RUNX factors [5].
• Moreover, we show that glide/gcm activates a new tendon cell gene independently of stripe [8].
• Here we show that glide/gcm is necessary to induce glial differentiation in the peripheral nervous system [9].
• In addition, gcm has a role in the differentiation of the plasmatocyte/macrophage lineage of hemocytes [10].

Associations of gcm with chemical compounds

• In the DNA-binding region of this GCM protein, there is a cysteine-rich region with which divalent metal ions such as Zn(2+) must bind and other proteins belonging to the GCM family have a corresponding region [11].

Physical interactions of gcm

• Eleven such GCM-binding sequences are found in the 5' upstream region of the repo gene, whose expression in early glial cells is dependent on gcm [6].

Regulatory relationships of gcm

• Notably, we demonstrate that GCM/GCM2 play a key role in controlling the size of the crystal cell population by inhibiting lz activation and maintenance [5].
• gcm2 promotes glial cell differentiation and is required with glial cells missing for macrophage development in Drosophila [10].
• In Drosophila lateral glial cell development is initiated by the transcription factor encoded by glial cells missing. glial cells missing activates downstream transcription factors such as repo and pointed which subsequently control terminal glial differentiation [12].
• During subsequent stages of embryonic development gcm and pointed appear to activate loco transcription synergistically [12].
• Within the dbd lineage, Notch is specifically activated in one of the daughter cells and is required for gcm expression and a glial fate [7].

Other interactions of gcm

• We show that, surprisingly, gcm is initially expressed in all prohemocytes but is rapidly downregulated in the anterior-most row of prohemocytes, which then initiates lz expression [5].
• This suggests that the GCM protein is a transcriptional regulator directly controlling repo [6].
• CycE, which is asymmetrically expressed after the first division of NB6-4t, functions upstream of pros and gcm to specify the neuronal sublineage [13].
• The expression of loco is initially dependent on gcm [12].
• Huckebein-mediated autoregulation of Glide/Gcm triggers glia specification [14].

Analytical, diagnostic and therapeutic context of gcm

• By PCR amplification, we obtained evidence for the existence of additional gcm-motif genes in mouse as well as in Drosophila [6].
• To identify gcm downstream genes in a comprehensive manner, we used genome-wide oligonucleotide arrays to analyze differential gene expression in wild-type embryos versus embryos in which gcm is misexpressed throughout the neuroectoderm [15].
• Sequence analysis suggested the presence of gcm and pointed DNA binding sites [12].
• Validation by in situ hybridization revealed expression in glial cells, macrophages, and tendon cells (all three cell types depend on gcm) for 70 genes, of which more than 50 had been unknown to be under gcm control [16].

References