View source for Eomesodermin

{{Infobox_gene}}
'''Eomesodermin''' also known as '''T-box brain protein 2''' (Tbr2) is a [[protein]] that in humans is encoded by the ''EOMES'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: Eomesodermin| url = https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=retrieve&list_uids=8320| accessdate = 2011-11-01 <!-- T22:27:07.474-07:00 --> }}</ref>

[[File:T box DNA binding domain.png|thumb|A representation of the T box DNA binding domain]]

The Eomesodermin/Tbr2 gene, ''EOMES'', encodes a member of a [[Conserved sequence|conserved protein family]] that shares a common DNA-binding domain, the [[T-box transcription factor TBX1|T-box]].<ref name="Arnold_2008" /> T-box genes encode  [[transcription factor]]s, which control [[gene expression]], involved in the regulation of developmental processes. Eomesodermin/Tbr2 itself controls regulation of [[Neural stem cell|radial glia,]] as well as other related cells.<ref name="Arnold_2008">{{cite journal | vauthors = Arnold SJ, Huang GJ, Cheung AF, Era T, Nishikawa S, Bikoff EK, Molnár Z, Robertson EJ, Groszer M | title = The T-box transcription factor Eomes/Tbr2 regulates neurogenesis in the cortical subventricular zone | journal = Genes & Development | volume = 22 | issue = 18 | pages = 2479–84 | year = 2008 | pmid = 18794345 | pmc = 2546697 | doi = 10.1101/gad.475408 }}</ref> Eomesodermin/Tbr2 has also been found to have a role in [[Immune system|immune response]], and there exists some loose evidence for its connections in other systems.<ref name="Zhu_2010" />

== Development ==

Eomesodermin/Tbr2 is expressed highly in the intermediate progenitor stage of the developing [[neuron]].<ref name="Englund_2005" /> Neurons, the primary functional cells of the brain, are developed from r[[Radial glial cell|adial glia cells]]. This process of cells developing into other types of cells is called [[Cellular differentiation|differentiation.]] Radial glia are present in the ventricular zone of the [[brain]], which are on the lateral walls of the [[lateral ventricles]].<ref>{{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 = 415–34 | date = Jan 2006 | pmid = 16320258 | doi = 10.1002/cne.20798 }}</ref> Radial glia [[Cell division|divide]] and migrate towards the surface of the brain, the cerebral [[Cortex (anatomy)|cortex]]. During this migration, there are three stages of cellular development: radial glia, intermediate progenitors, and postmitotic projection neurons.<ref name="Englund_2005" /> Radial glia express [[PAX6|Pax6]], while intermediate progenitor cells express Eomesodermin/Tbr2, and postmitotic projection neurons express [[TBR1|Tbr1]].<ref name="Englund_2005" /> 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 [[Neural development|neurodevelopment]].<ref name="Englund_2005">{{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 = 247–51 | date = Jan 2005 | pmid = 15634788 | doi = 10.1523/JNEUROSCI.2899-04.2005 }}</ref> However, neurogenesis has been found to occur to some extent in the ventricular zone in fully developed organisms.<ref>{{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 }}</ref>

[[File:Human subventricular zone.jpg|thumb|Subventricular Zone|left]]
[[File:Cerebral Cortex location.jpg|thumb|Cerebral Cortex]]

It has been found experimentally through [[Gene knockout|knock out studies]], that mice lacking Eomesodermin/Tbr2 during early development have a reduced number of actively dividing cells, called [[Cell growth|proliferating cells]], in the [[subventricular zone]], a key area of neurogenesis in the brain.<ref name="Sessa_2008" /> This, may lead to the [[microcephaly]] (small head size due to improper brain development) seen in Eomesodermin/Tbr2 deficient mice.<ref name="Sessa_2008" /> Eomesodermin/Tbr2 lacking mice have smaller upper [[Cerebral cortex|cortical layers]] and a smaller [[Subventricular zone|sub ventricular zone]] in the brain, and have an absence of a [[Olfactory bulb mitral cell|mitral cell]] (neurons involved in the olfactory pathway) layer, with mitral cells instead being scattered about.<ref name="Sessa_2008" /> On the behavioral side, Eomesodermin/Tbr2 lacking mice show high [[anger]] levels and perform [[infanticide]].<ref name="Arnold_2008" /> Eomesodermin/Tbr2 lacking mice also seem to have problems with long [[axon]] connections.<ref name="Sessa_2008" /> Axons are projections from neurons that connect with other cells in what is called a [[synapse]] and send [[neurotransmitter]]s. 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 fiber]]s, which connect the two [[Hemispheres of the brain|hemispheres]] of the brain, and lack the [[corpus callosum]], another region of the brain involved in hemisphere connections.<ref name="Sessa_2008">{{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 glish | journal = Neuron | volume = 60 | issue = 1 | pages = 56–69 | date = Oct 2008 | pmid = 18940588 | pmc = 2887762 | doi = 10.1016/j.neuron.2008.09.028 }}</ref>

[[File:Microcephaly-comparison-500px.jpg|thumb|Microcephaly|left]]

Eomesodermin/Tbr2 has also been implicated in other key development systems. It was found

that early in development, Eomesodermin/Tbr2 controls early differentiation of the [[Heart|cardiac]] [[mesoderm]].<ref name="Costello_2011" /> In fact, lack of Eomesodermin/Tbr2 seems to cause cells to fail to differentiate into [[Cardiac muscle cell|cardiomyocytes]], which are heart muscle cells. Eomesodermin/Tbr2 controls the expression of cardiac specific genes [[MESP1|Mesp1]], [[MYL7|Myl7]], [[MYL2|Myl2]], [[Myocardin]],Nkx2.5 and [[MEF2C|Mef2c]].<ref name="Costello_2011">{{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 = 1084–91 | date = Sep 2011 | pmid = 21822279 | pmc = 4531310 | doi = 10.1038/ncb2304 }}</ref>

 [[File:Human heart.png|left|thumb|The human heart, with cardiac muscles]]

Additionally, although neurogenesis occurs primarily in the early stages of development, there are locations within the brain that have been discovered to perform neurogenesis into [[adult]]hood.<ref name="Zhu_2010" /> One of these areas, the [[hippocampus]], which is involved in [[memory]] formation, shows decreased neurogenesis when Eomesodermin/Tbr2 is removed.<ref name="Hodge_2012" /> It was also found that Eomesodermin/Tbr2 functions by reducing amounts of [[SOX2|Sox2]], which is associated with radial glia.<ref name="Hodge_2012">{{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 = 6275–87 | date = May 2012 | pmid = 22553033 | pmc = 3366485 | doi = 10.1523/JNEUROSCI.0532-12.2012 }}</ref> Another study found that mice without Eomesodermin/Tbr2 lacked [[Long-term memory|long term memory]] formation, which may relate to Eomesodermin/Tbr2's effects on the hippocampus.

<ref>{{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 }}</ref>

== Immune response ==

[[File:Healthy Human T Cell.jpg|thumb|Scanning electron micrograph of a human T cell]]

Eomesodermin/Tbr2 is highly expressed in [[Cytotoxic T cell|CD8+ T cells]], but not [[T helper cell|CD4+ T cells]].<ref name="Zhu_2010" /> CD4+ T cells are the helper [[T cell]]s 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.<ref name="Zhu_2010" /> Lack of Eomesodermin/Tbr2, alongside [[TBX21|T bet]]  another T box protein caused CD8+ T cells to not penetrate [[tumors]] so they could perform their anti cancer duties.<ref name="Zhu_2010" /> 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.<ref name="Zhu_2010" /> Despite Eomesodermin/Tbr2 playing a role in the ability of CD8+ T cells to penetrate tumors, it only plays a small role in production of [[Interferon-gamma]], which is a molecule that communicates to other immune cells during an immune response.<ref name="Zhu_2010">{{cite journal | vauthors = Zhu Y, Ju S, Chen E, Dai S, Li C, Morel P, Liu L, Zhang X, Lu B | title = T-bet and eomesodermin are required for T cell-mediated antitumor immune responses  | journal = Journal of Immunology | volume = 185 | issue = 6 | pages = 3174–83 | date = Sep 2010 | pmid = 20713880 | doi = 10.4049/jimmunol.1000749 }}</ref>

== See also ==
* [[T-box]] family
* [[TBR1]]

== References ==
{{reflist|33em}}

==Further reading ==
 {{refbegin |33em}}
* {{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 = 183–93 | date = Jun 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 = 1236–44 | date = Dec 2005 | pmid = 16273099 | doi = 10.1038/ni1268 }}
* {{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 = 454–6 | date = Apr 2007 | pmid = 17353897 | doi = 10.1038/ng1993 }}
* {{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 = 1572–8 | date = Nov 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 = 8102–8 | date = Jun 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 = Oct 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 = 92–8 | date = Apr 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 = 31–4 | date = Jan 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 | year = 2010 | pmid = 20498708 | pmc = 2869357 | doi = 10.1371/journal.pone.0010636 | editor1-last = Unutmaz | 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 = 7151–5 | date = Dec 2010 | pmid = 21076068 | pmc = 2997140 | doi = 10.4049/jimmunol.1003193 }}
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{{Transcription factors|g4}}

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[[Category:Transcription factors]]