Eomesodermin

Eomesodermin/Tbr2 is expressed highly in the intermediate progenitor stage of the developing neuron. 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.{{cite journal | vauthors = Quiñones-Hinojosa A, Sanai N, Soriano-Navarro M, Gonzalez-Perez O, Mirzadeh Z, Gil-Perotin S, Romero-Rodriguez R, Berger MS, Garcia-Verdugo JM, Alvarez-Buylla A | title = Cellular composition and cytoarchitecture of the adult human subventricular zone: a niche of neural stem cells | journal = The Journal of Comparative Neurology | volume = 494 | issue = 3 | pages = 415–434 | date = January 2006 | pmid = 16320258 | doi = 10.1002/cne.20798 | s2cid = 11713373 }} 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. Radial glia express Pax6, while intermediate progenitor cells express Eomesodermin/Tbr2, and postmitotic projection neurons express Tbr1. 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.

File:Microcephaly-comparison-500px.jpg

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. {{cite journal | vauthors = Hodge RD, Kowalczyk TD, Wolf SA, Encinas JM, Rippey C, Enikolopov G, Kempermann G, Hevner RF | title = Intermediate progenitors in adult hippocampal neurogenesis: Tbr2 expression and coordinate regulation of neuronal output | journal = The Journal of Neuroscience | volume = 28 | issue = 14 | pages = 3707–3717 | date = April 2008 | pmid = 18385329 | pmc = 6671086 | doi = 10.1523/JNEUROSCI.4280-07.2008 | doi-access = free }}

Tbr2 inactivation has also been tied to deficiencies in cortical neurogenesis further suggesting the importance of the cascade in activating and maintaining neuron production.{{cite journal | vauthors = Kowalczyk T, Pontious A, Englund C, Daza RA, Bedogni F, Hodge R, Attardo A, Bell C, Huttner WB, Hevner RF | title = Intermediate neuronal progenitors (basal progenitors) produce pyramidal-projection neurons for all layers of cerebral cortex | journal = Cerebral Cortex | volume = 19 | issue = 10 | pages = 2439–2450 | date = October 2009 | pmid = 19168665 | pmc = 2742596 | doi = 10.1093/cercor/bhn260 }} 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. This, may lead to the microcephaly (small head size due to improper brain development) seen in Eomesodermin/Tbr2 deficient mice. 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. Phenotypically, Eomesodermin/Tbr2 lacking mice show high anger levels and perform infanticide. Eomesodermin/Tbr2 lacking mice also seem to have problems with long axon connections. 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.{{cite journal | vauthors = Sessa A, Mao CA, Hadjantonakis AK, Klein WH, Broccoli V | title = Tbr2 directs conversion of radial glia into basal precursors and guides neuronal amplification by indirect neurogenesis in the developing neocortex | journal = Neuron | volume = 60 | issue = 1 | pages = 56–69 | date = October 2008 | pmid = 18940588 | pmc = 2887762 | doi = 10.1016/j.neuron.2008.09.028 }}

There are locations within the brain that have been discovered to perform neurogenesis into adulthood,{{cite journal | vauthors = Englund C, Fink A, Lau C, Pham D, Daza RA, Bulfone A, Kowalczyk T, Hevner RF | title = Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex | journal = The Journal of Neuroscience | volume = 25 | issue = 1 | pages = 247–251 | date = January 2005 | pmid = 15634788 | pmc = 6725189 | doi = 10.1523/JNEUROSCI.2899-04.2005 | doi-access = free }} including the ventricular zone.{{cite journal | vauthors = Ming GL, Song H | title = Adult neurogenesis in the mammalian brain: significant answers and significant questions | journal = Neuron | volume = 70 | issue = 4 | pages = 687–702 | date = May 2011 | pmid = 21609825 | pmc = 3106107 | doi = 10.1016/j.neuron.2011.05.001 }} The hippocampus, which is involved in memory formation, shows decreased neurogenesis when Eomesodermin/Tbr2 is removed.{{cite journal | vauthors = Hodge RD, Nelson BR, Kahoud RJ, Yang R, Mussar KE, Reiner SL, Hevner RF | title = Tbr2 is essential for hippocampal lineage progression from neural stem cells to intermediate progenitors and neurons | journal = The Journal of Neuroscience | volume = 32 | issue = 18 | pages = 6275–6287 | date = May 2012 | pmid = 22553033 | pmc = 3366485 | doi = 10.1523/JNEUROSCI.0532-12.2012 }} It was also found that Eomesodermin/Tbr2 functions by reducing amounts of Sox2, which is associated with radial glia. Another study found that mice without Eomesodermin/Tbr2 lacked long term memory formation, which may relate to Eomesodermin/Tbr2's effects on the hippocampus.{{cite journal | vauthors = Knox JJ, Cosma GL, Betts MR, McLane LM | title = Characterization of T-bet and eomes in peripheral human immune cells | journal = Frontiers in Immunology | volume = 5 | pages = 217 | date = 2014-05-14 | pmid = 24860576 | pmc = 4030168 | doi = 10.3389/fimmu.2014.00217 | doi-access = free }}

Early in development, Eomesodermin/Tbr2 controls early differentiation of the cardiac mesoderm. 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.{{cite journal | vauthors = Costello I, Pimeisl IM, Dräger S, Bikoff EK, Robertson EJ, Arnold SJ | title = The T-box transcription factor Eomesodermin acts upstream of Mesp1 to specify cardiac mesoderm during mouse gastrulation | journal = Nature Cell Biology | volume = 13 | issue = 9 | pages = 1084–1091 | date = August 2011 | pmid = 21822279 | pmc = 4531310 | doi = 10.1038/ncb2304 }}

Eomesodermin/Tbr2 is highly expressed in CD8+ T cells, but not CD4+ T cells. 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. 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. 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.

• T-box family
• TBR1

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• {{cite journal | vauthors = Kimura N, Nakashima K, Ueno M, Kiyama H, Taga T | title = A novel mammalian T-box-containing gene, Tbr2, expressed in mouse developing brain | journal = Brain Research. Developmental Brain Research | volume = 115 | issue = 2 | pages = 183–193 | date = June 1999 | pmid = 10407135 | doi = 10.1016/s0165-3806(99)00064-4 }}
• {{cite journal | vauthors = Intlekofer AM, Takemoto N, Wherry EJ, Longworth SA, Northrup JT, Palanivel VR, Mullen AC, Gasink CR, Kaech SM, Miller JD, Gapin L, Ryan K, Russ AP, Lindsten T, Orange JS, Goldrath AW, Ahmed R, Reiner SL | title = Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin | journal = Nature Immunology | volume = 6 | issue = 12 | pages = 1236–1244 | date = December 2005 | pmid = 16273099 | doi = 10.1038/ni1268 | s2cid = 10917617 }}
• {{cite journal | vauthors = Baala L, Briault S, Etchevers HC, Laumonnier F, Natiq A, Amiel J, Boddaert N, Picard C, Sbiti A, Asermouh A, Attié-Bitach T, Encha-Razavi F, Munnich A, Sefiani A, Lyonnet S | title = Homozygous silencing of T-box transcription factor EOMES leads to microcephaly with polymicrogyria and corpus callosum agenesis | journal = Nature Genetics | volume = 39 | issue = 4 | pages = 454–456 | date = April 2007 | pmid = 17353897 | doi = 10.1038/ng1993 | s2cid = 9421118 }}
• {{cite journal | vauthors = Atreya I, Schimanski CC, Becker C, Wirtz S, Dornhoff H, Schnürer E, Berger MR, Galle PR, Herr W, Neurath MF | title = The T-box transcription factor eomesodermin controls CD8 T cell activity and lymph node metastasis in human colorectal cancer | journal = Gut | volume = 56 | issue = 11 | pages = 1572–1578 | date = November 2007 | pmid = 17566017 | pmc = 2095672 | doi = 10.1136/gut.2006.117812 }}
• {{cite journal | vauthors = Araki Y, Fann M, Wersto R, Weng NP | title = Histone acetylation facilitates rapid and robust memory CD8 T cell response through differential expression of effector molecules (eomesodermin and its targets: perforin and granzyme B) | journal = Journal of Immunology | volume = 180 | issue = 12 | pages = 8102–8108 | date = June 2008 | pmid = 18523274 | pmc = 2493419 | doi = 10.4049/jimmunol.180.12.8102 }}
• {{cite journal | vauthors = Sessa A, Mao CA, Hadjantonakis AK, Klein WH, Broccoli V | title = Tbr2 directs conversion of radial glia into basal precursors and guides neuronal amplification by indirect neurogenesis in the developing neocortex | journal = Neuron | volume = 60 | issue = 1 | pages = 56–69 | date = October 2008 | pmid = 18940588 | pmc = 2887762 | doi = 10.1016/j.neuron.2008.09.028 }}
• {{cite journal | vauthors = D'Cruz LM, Rubinstein MP, Goldrath AW | title = Surviving the crash: transitioning from effector to memory CD8+ T cell | journal = Seminars in Immunology | volume = 21 | issue = 2 | pages = 92–98 | date = April 2009 | pmid = 19269192 | pmc = 2671236 | doi = 10.1016/j.smim.2009.02.002 }}
• {{cite journal | vauthors = Wang HT, Ge XS, Xue ZP, Li BQ | title = [Role of transcription factor T-bet and Eomes in IFN-gamma secretion of different human T cell subsets] | journal = Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology | volume = 26 | issue = 1 | pages = 31–34 | date = January 2010 | pmid = 20056084 }}
• {{cite journal | vauthors = Narayanan S, Silva R, Peruzzi G, Alvarez Y, Simhadri VR, Debell K, Coligan JE, Borrego F | title = Human Th1 cells that express CD300a are polyfunctional and after stimulation up-regulate the T-box transcription factor eomesodermin | journal = PLOS ONE | volume = 5 | issue = 5 | pages = e10636 | date = May 2010 | pmid = 20498708 | pmc = 2869357 | doi = 10.1371/journal.pone.0010636 | editor1-last = Unutmaz | doi-access = free | bibcode = 2010PLoSO...510636N | editor1-first = Derya }}
• {{cite journal | vauthors = Kinjyo I, Gordon SM, Intlekofer AM, Dowdell K, Mooney EC, Caricchio R, Grupp SA, Teachey DT, Rao VK, Lindsten T, Reiner SL | title = Cutting edge: Lymphoproliferation caused by Fas deficiency is dependent on the transcription factor eomesodermin | journal = Journal of Immunology | volume = 185 | issue = 12 | pages = 7151–7155 | date = December 2010 | pmid = 21076068 | pmc = 2997140 | doi = 10.4049/jimmunol.1003193 }}

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{{Transcription factors|g4}}

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Category:Transcription factors