Eomesodermin

EOMES
Identifiers
Aliases	EOMES, TBR2, Eomesodermin
External IDs	OMIM: 604615; MGI: 1201683; HomoloGene: 3971; GeneCards: EOMES; OMA:EOMES - orthologs
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3p24.1 Start 27,715,949 bp[1] End 27,722,711 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9 70.21 cM|9 F3 Start 118,307,280 bp[2] End 118,315,200 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ganglionic eminence ventricular zone granulocyte cerebellar vermis cerebellar hemisphere testicle right hemisphere of cerebellum lymph node blood spleen Top expressed in ventricular zone olfactory bulb epiblast blastocyst blastocyst embryo cerebellar vermis mesoderm blood embryo More reference expression data BioGPS n/a
Gene ontology Molecular function RNA polymerase II transcription regulatory region sequence-specific DNA binding chromatin binding sequence-specific DNA binding DNA-binding transcription factor activity DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleus intracellular anatomical structure Biological process stem cell population maintenance regulation of transcription by RNA polymerase II positive regulation of transcription, DNA-templated regulation of neurogenesis gastrulation trophectodermal cell differentiation skeletal muscle cell differentiation adaptive immune response multicellular organism development cell differentiation blastocyst development regulation of transcription, DNA-templated cerebral cortex neuron differentiation regulation of neuron differentiation CD8-positive, alpha-beta T cell differentiation involved in immune response transcription, DNA-templated olfactory bulb development endodermal cell fate specification cerebral cortex regionalization cardioblast differentiation immune system process positive regulation of cell differentiation positive regulation of transcription by RNA polymerase II brain development regulation of gene expression mesoderm formation negative regulation of transcription by RNA polymerase II mesodermal to mesenchymal transition involved in gastrulation endoderm formation cell differentiation involved in embryonic placenta development negative regulation of DNA-binding transcription factor activity neurogenesis neuron differentiation endoderm development anatomical structure morphogenesis mesendoderm development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8320 13813 Ensembl ENSG00000163508 ENSMUSG00000032446 UniProt O95936 O54839 RefSeq (mRNA) NM_001278182 NM_001278183 NM_005442 NM_001164789 NM_010136 RefSeq (protein) NP_001265111 NP_001265112 NP_005433 NP_001158261 NP_034266 Location (UCSC) Chr 3: 27.72 – 27.72 Mb Chr 9: 118.31 – 118.32 Mb PubMed search [3] [4]
Wikidata
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Eomesodermin also known as T-box brain protein 2 (Tbr2) is a protein that in humans is encoded by the EOMES gene.^[5]

The Eomesodermin/Tbr2 gene, EOMES, encodes a member of a conserved protein family that shares a common DNA-binding domain, the T-box.^[6] T-box genes encode transcription factors, which control gene expression, involved in the regulation of developmental processes. Eomesodermin/Tbr2 itself controls regulation of radial glia, as well as other related cells.^[6] Eomesodermin/Tbr2 has also been found to have a role in immune response, and there exists some loose evidence for its connections in other systems.^[7]

Eomesodermin/Tbr2 is expressed highly in the intermediate progenitor stage of the developing neuron.^[8] Neurons, the primary functional cells of the brain, are developed from radial glia cells. This process of cells developing into other types of cells is called differentiation. Radial glia are present in the ventricular zone of the brain, which are on the lateral walls of the lateral ventricles.^[9] Radial glia divide and migrate towards the surface of the brain, the cerebral cortex. During this migration, there are three stages of cellular development: radial glia, intermediate progenitors, and postmitotic projection neurons.^[8] Radial glia express Pax6, while intermediate progenitor cells express Eomesodermin/Tbr2, and postmitotic projection neurons express Tbr1.^[8] This process, known as neurogenesis, occurs mainly in the developing cortex before the organism has fully developed, and thus Eomesodermin/Tbr2 has been implicated in neurodevelopment.

Tbr2 has been observed in a transcription factor cascade to enable to development of glutamatergic neurons. Pax6, as expressed by radial glia cells, activates the transcription of Neurogenin-2 which then activates the generation of intermediate progenitor cells (IPC) expressing Tbr2. These cells are localized within the subventricular zone. The IPCs then undergo symmetric division to produce NeuroD expressing cells that can differentiate in TBR1 neurons. Similar mechanisms have been observed in both embryonic and adult neurogenesis.^[10]

Tbr2 inactivation has also been tied to deficiencies in cortical neurogenesis further suggesting the importance of the cascade in activating and maintaining neuron production.^[11] It has been found experimentally through knockout studies that mice lacking Eomesodermin/Tbr2 during early development have a reduced number of actively dividing cells, called proliferating cells, in the subventricular zone.^[12] This, may lead to the microcephaly (small head size due to improper brain development) seen in Eomesodermin/Tbr2 deficient mice.^[12] Eomesodermin/Tbr2 lacking mice have smaller upper cortical layers and a smaller sub ventricular zone in the brain, and have an absence of a mitral cell (neurons involved in the olfactory pathway) layer, with mitral cells instead being scattered about.^[12] Phenotypically, Eomesodermin/Tbr2 lacking mice show high anger levels and perform infanticide.^[6] Eomesodermin/Tbr2 lacking mice also seem to have problems with long axon connections.^[12] Axons are projections from neurons that connect with other cells in what is called a synapse and send neurotransmitters. In this way, they can communicate with other cells, and form the processing that allows are brains to function. Eomesodermin/Tbr2 lacking mice seem to lack fully formed commissural fibers, which connect the two hemispheres of the brain, and lack the corpus callosum, another region of the brain involved in hemisphere connections.^[12]

There are locations within the brain that have been discovered to perform neurogenesis into adulthood,^[7][8] including the ventricular zone.^[13] The hippocampus, which is involved in memory formation, shows decreased neurogenesis when Eomesodermin/Tbr2 is removed.^[14] It was also found that Eomesodermin/Tbr2 functions by reducing amounts of Sox2, which is associated with radial glia.^[14] Another study found that mice without Eomesodermin/Tbr2 lacked long term memory formation, which may relate to Eomesodermin/Tbr2's effects on the hippocampus.^[15]

Early in development, Eomesodermin/Tbr2 controls early differentiation of the cardiac mesoderm.^[16] Lack of Eomesodermin/Tbr2 appears to be correlated with failure to differentiate into cardiomyocytes. Eomesodermin/Tbr2 controls the expression of cardiac specific genes Mesp1, Myl7, Myl2, Myocardin, Nkx2.5 and Mef2c.^[16]

Eomesodermin/Tbr2 is highly expressed in CD8+ T cells, but not CD4+ T cells.^[7] CD4+ T cells are the helper T cells which detect foreign particles in the body, and call CD8+ T cells to facilitate death of the foreign particles. Eomesodermin/Tbr2 was found to play a role in the anti cancer properties of CD8+ T cells.^[7] Lack of Eomesodermin/Tbr2, alongside T bet, another T box protein, caused CD8+ T cells to not penetrate tumors so they could perform their anti cancer duties.^[7] Eomesodermin/Tbr2 prevents CD8+ cells from differentiating into other types of T cells, but does not play a role in the production of CD8+ T cells itself.^[7]

• T-box family
• TBR1

This article incorporates text from the United States National Library of Medicine, which is in the public domain.