|, TBR2, Eomesodermin|
|Genetically Related Diseases|
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The Eomesodermin/Tbr2 gene, EOMES, encodes a member of a conserved protein family that shares a common DNA-binding domain, the T-box. 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. 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.
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 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. However, neurogenesis has been found to occur to some extent in the ventricular zone in fully developed organisms.
It has been found experimentally through knock out studies, that mice lacking Eomesodermin/Tbr2 during early development have a reduced number of actively dividing cells, called proliferating cells, in the subventricular zone, a key area of neurogenesis in the brain. 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. On the behavioral side, 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.
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, which are heart muscle cells. 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 into adulthood. One of these areas, the hippocampus, which is involved in memory formation, 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, which may relate to Eomesodermin/Tbr2's effects on the hippocampus.
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 proteincaused 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. 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.
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