Eomesodermin also known asT-box brain protein 2 (Tbr2) is aprotein that in humans is encoded by theEOMESgene.[5]
A representation of the T box DNA binding domain
The Eomesodermin/Tbr2 gene,EOMES, encodes a member of aconserved protein family that shares a common DNA-binding domain, theT-box.[6] T-box genes encodetranscription factors, which controlgene expression, involved in the regulation of developmental processes. Eomesodermin/Tbr2 itself controls regulation ofradial glia, as well as other related cells.[6] Eomesodermin/Tbr2 has also been found to have a role inimmune 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 developingneuron.[8] Neurons, the primary functional cells of the brain, are developed fromradial glia cells. This process of cells developing into other types of cells is calleddifferentiation. Radial glia are present in the ventricular zone of thebrain, which are on the lateral walls of thelateral ventricles.[9] Radial gliadivide and migrate towards the surface of the brain, the cerebralcortex. During this migration, there are three stages of cellular development: radial glia,intermediate progenitors, and postmitotic projection neurons.[8] Radial glia expressPax6, while intermediate progenitor cells express Eomesodermin/Tbr2, and postmitotic projection neurons expressTbr1.[8] This process, known asneurogenesis, occurs mainly in the developing cortex before the organism has fully developed, and thus Eomesodermin/Tbr2 has been implicated inneurodevelopment.
Microcephaly
Tbr2 has been observed in a transcription factor cascade to enable to development ofglutamatergic neurons. Pax6, as expressed by radial glia cells, activates the transcription ofNeurogenin-2 which then activates the generation of intermediate progenitor cells (IPC) expressing Tbr2. These cells are localized within thesubventricular zone. The IPCs then undergosymmetric division to produceNeuroD expressing cells that can differentiate inTBR1 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 throughknockout studies that mice lacking Eomesodermin/Tbr2 during early development have a reduced number of actively dividing cells, calledproliferating cells, in thesubventricular zone.[12] This, may lead to themicrocephaly (small head size due to improper brain development) seen in Eomesodermin/Tbr2 deficient mice.[12] Eomesodermin/Tbr2 lacking mice have smaller uppercortical layers and a smallersub ventricular zone in the brain, and have an absence of amitral cell (neurons involved in the olfactory pathway) layer, with mitral cells instead being scattered about.[12] Phenotypically, Eomesodermin/Tbr2 lacking mice show highanger levels and performinfanticide.[6] Eomesodermin/Tbr2 lacking mice also seem to have problems with longaxon connections.[12] Axons are projections from neurons that connect with other cells in what is called asynapse and sendneurotransmitters. 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 formedcommissural fibers, which connect the twohemispheres of the brain, and lack thecorpus callosum, another region of the brain involved in hemisphere connections.[12]
There are locations within the brain that have been discovered to perform neurogenesis intoadulthood,[7][8] including the ventricular zone.[13] Thehippocampus, which is involved inmemory formation, shows decreased neurogenesis when Eomesodermin/Tbr2 is removed.[14] It was also found that Eomesodermin/Tbr2 functions by reducing amounts ofSox2, which is associated with radial glia.[14] Another study found that mice without Eomesodermin/Tbr2 lackedlong term memory formation, which may relate to Eomesodermin/Tbr2's effects on the hippocampus.[15]
Early in development, Eomesodermin/Tbr2 controls early differentiation of thecardiacmesoderm.[16] Lack of Eomesodermin/Tbr2 appears to be correlated with failure to differentiate intocardiomyocytes. Eomesodermin/Tbr2 controls the expression of cardiac specific genesMesp1,Myl7,Myl2,Myocardin, Nkx2.5 andMef2c.[16]
Eomesodermin/Tbr2 is highly expressed inCD8+ T cells, but notCD4+ T cells.[7] CD4+ T cells are the helperT 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 anticancer properties of CD8+ T cells.[7] Lack of Eomesodermin/Tbr2, alongsideT bet, another T box protein, caused CD8+ T cells to not penetratetumors 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]
^Quiñones-Hinojosa A, Sanai N, Soriano-Navarro M, Gonzalez-Perez O, Mirzadeh Z, Gil-Perotin S, et al. (January 2006). "Cellular composition and cytoarchitecture of the adult human subventricular zone: a niche of neural stem cells".The Journal of Comparative Neurology.494 (3):415–434.doi:10.1002/cne.20798.PMID16320258.S2CID11713373.
Kimura N, Nakashima K, Ueno M, Kiyama H, Taga T (June 1999). "A novel mammalian T-box-containing gene, Tbr2, expressed in mouse developing brain".Brain Research. Developmental Brain Research.115 (2):183–193.doi:10.1016/s0165-3806(99)00064-4.PMID10407135.
Intlekofer AM, Takemoto N, Wherry EJ, Longworth SA, Northrup JT, Palanivel VR, et al. (December 2005). "Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin".Nature Immunology.6 (12):1236–1244.doi:10.1038/ni1268.PMID16273099.S2CID10917617.
Baala L, Briault S, Etchevers HC, Laumonnier F, Natiq A, Amiel J, et al. (April 2007). "Homozygous silencing of T-box transcription factor EOMES leads to microcephaly with polymicrogyria and corpus callosum agenesis".Nature Genetics.39 (4):454–456.doi:10.1038/ng1993.PMID17353897.S2CID9421118.
Wang HT, Ge XS, Xue ZP, Li BQ (January 2010). "[Role of transcription factor T-bet and Eomes in IFN-gamma secretion of different human T cell subsets]".Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology.26 (1):31–34.PMID20056084.
