Eomesodermin

Template:PBB Eomesodermin also known as T-box brain protein 2 (Tbr2) is a protein that in humans is encoded by the EOMES gene.

The Eomesodermin/Tbr2 gene encodes a member of a conserved protein family that shares a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. Eomesodermin/Tbr2 itself controls regulation of radial glia, amongst other things. 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.

Development

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. Radial glia divide and migrate towards the surface of the 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 occurs mainly in the developing cortex, and thus Eomesodermin/Tbr2 has been implicated in neurodevelopment.

It has been found experimentally that mice lacking Eomesodermin/Tbr2 during early development have a reduced number of proliferating cells in the subventricular zone, a key area of neurogenesis (the production of new neurons) in the brain. This in turn, may lead to the resulting microcephaly seen in Eomesodermin/Tbr2 deficient mice. Eomesodermin/Tbr2 lacking mice show reduced volume in the upper cortical layers and sub ventricular zone of the brain, and an absence of a mitral cell (neurons involved in the olfactory pathway) layer, with mitral cells instead being scattered about. Finally, on the behavioral side, Eomesodermin/Tbr2 lacking mice show high anger levels and perform infanticide. Finally, Eomesodermin/Tbr2 mutants also seem to have problems with long axon connections. Eomesodermin/Tbr2 mutants seem to lack fully formed commissural fibers, which connect the two hemispheres of the brain, and lack the corpus callosum.

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 cardiac mesoderm. In fact, lack of Eomesodermin/Tbr2 seems to cause cells to fail to differentiate into cardiomyocytes. Eomesodermin/Tbr2 controls the expression of cardiac specific genes Mesp1, Myl7, Myl2, Myocardin,Nkx2.5 and Mef2c.

Additionally, although neurogenesis occurs primarily in the early stages of development, there are locations within the brain that have been discovered to perform neurogenesis, even into adulthood. One of these areas, the hippocampus, shows decreased neurogenesis when Eomesodermin/Tbr2 is removed. 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.

A representation of the T box DNA binding domain

Immune Response

It was also found that Eomesodermin/Tbr2 was highly expressed in CD8+ T cells, but not CD4+ T cells. Eomesodermin/Tbr2 was found to play a role in the anti cancer properties of CD8+ T cells. Lack of Eomesodermin/Tbr2, alongside T bet, caused CD8+ T cells to not penetrate tumors. 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. Moreover, despite Eomesodermin/Tbr2 playing a role in the ability of CD8+ T cells penetrating tumors, it does not play a crucial role in Interferon-gamma production, which begins after antigen specific immunity develops, but does play some small role.

See also

• T-box family
• TBR1

Further reading

• Kimura, N.; Nakashima, K.; Ueno, M.; Kiyama, H.; Taga, T. (1999). "A novel mammalian T-box-containing gene, Tbr2, expressed in mouse developing brain". Brain research. Developmental brain research. 115 (2): 183–193. PMID 10407135.
• Intlekofer, A. M.; Takemoto, N.; Wherry, E. J.; Longworth, S. A.; Northrup, J. T.; Palanivel, V. R.; Mullen, A. C.; Gasink, C. R.; Kaech, S. M.; Miller, J. D.; Gapin, L.; Ryan, K.; Russ, A. P.; Lindsten, T.; Orange, J. S.; Goldrath, A. W.; Ahmed, R.; Reiner, S. L. (2005). "Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin". Nature Immunology. 6 (12): 1236–1244. doi:10.1038/ni1268. PMID 16273099.
• Baala, L.; Briault, S.; Etchevers, H. C.; Laumonnier, F. D. R.; Natiq, A.; Amiel, J.; Boddaert, N.; Picard, C.; Sbiti, A.; Asermouh, A.; Attié-Bitach, T.; Encha-Razavi, F. R. C.; Munnich, A.; Sefiani, A.; Lyonnet, S. (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. PMID 17353897.
• Atreya, I.; Schimanski, C. C.; Becker, C.; Wirtz, S.; Dornhoff, H.; Schnürer, E.; Berger, M. R.; Galle, P. R.; Herr, W.; Neurath, M. F. (2007). "The T‐box transcription factor eomesodermin controls CD8 T cell activity and lymph node metastasis in human colorectal cancer". Gut. 56 (11): 1572–1578. doi:10.1136/gut.2006.117812. PMC 2095672. PMID 17566017.
• Araki, Y.; Fann, M.; Wersto, R.; Weng, N. P. (2008). "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 of immunology (Baltimore, Md. : 1950). 180 (12): 8102–8108. doi:10.4049/jimmunol.180.12.8102. PMC 2493419. PMID 18523274.
• Sessa, A.; Mao, C. A.; Hadjantonakis, A. K.; Klein, W. H.; Broccoli, V. (2008). "Tbr2 Directs Conversion of Radial Glia into Basal Precursors and Guides Neuronal Amplification by Indirect Neurogenesis in the Developing Neocortex". Neuron. 60 (1): 56–69. doi:10.1016/j.neuron.2008.09.028. PMC 2887762. PMID 18940588.
• d’Cruz, L. M.; Rubinstein, M. P.; Goldrath, A. W. (2009). "Surviving the crash: Transitioning from effector to memory CD8+ T cell". Seminars in Immunology. 21 (2): 92–98. doi:10.1016/j.smim.2009.02.002. PMC 2671236. PMID 19269192.
• Wang, H. T.; Ge, X. S.; Xue, Z. P.; Li, B. Q. (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. PMID 20056084.
• Narayanan, S.; Silva, R.; Peruzzi, G.; Alvarez, Y.; Simhadri, V. R.; Debell, K.; Coligan, J. E.; Borrego, F. (2010). Unutmaz, Derya (ed.). "Human Th1 Cells That Express CD300a Are Polyfunctional and After Stimulation Up-Regulate the T-Box Transcription Factor Eomesodermin". PLoS ONE. 5 (5): e10636. doi:10.1371/journal.pone.0010636. PMC 2869357. PMID 20498708.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• Kinjyo, I.; Gordon, S. M.; Intlekofer, A. M.; Dowdell, K.; Mooney, E. C.; Caricchio, R.; Grupp, S. A.; Teachey, D. T.; Rao, V. K.; Lindsten, T.; Reiner, S. L. (2010). "Lymphoproliferation Caused by Fas Deficiency is Dependent on the Transcription Factor Eomesodermin". The Journal of Immunology. 185 (12): 7151–7155. doi:10.4049/jimmunol.1003193. PMC 2997140. PMID 21076068.

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