Eomesodermin also known as T-box brain protein 2 (Tbr2) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''EOMES''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

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 refers to a group of transcription factors involved in embryo, embryonic limb development, limb and heart development. Every T-box protein has a relatively large DNA-binding domain, generally comprising about a third of the entire protein ...

. T-box genes encode

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...

s, which control

gene expression Gene expression is the process (including its Regulation of gene expression, regulation) by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, ...

, involved in the regulation of developmental processes. Eomesodermin/Tbr2 itself controls regulation of

radial glia Radial glial cells, or radial glial progenitor cells (RGPs), are bipolar-shaped progenitor cells that are responsible for producing all of the neurons in the cerebral cortex. RGPs also produce certain lineages of glia, including astrocytes and ol ...

, as well as other related cells. Eomesodermin/Tbr2 has also been found to have a role in

immune response An immune response is a physiological reaction which occurs within an organism in the context of inflammation for the purpose of defending against exogenous factors. These include a wide variety of different toxins, viruses, intra- and extracellula ...

, and there exists some loose evidence for its connections in other systems.

Nervous system development

Neurogenesis

Eomesodermin/Tbr2 is expressed highly in the intermediate progenitor stage of the developing

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

. 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 The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

, which are on the lateral walls of the

lateral ventricles The lateral ventricles are the two largest ventricles of the brain and contain cerebrospinal fluid. Each cerebral hemisphere contains a lateral ventricle, known as the left or right lateral ventricle, respectively. Each lateral ventricle resemb ...

. Radial glia divide and migrate towards the surface of the brain, the cerebral

cortex Cortex or cortical may refer to: Biology * Cortex (anatomy), the outermost layer of an organ ** Cerebral cortex, the outer layer of the vertebrate cerebrum, part of which is the ''forebrain'' *** Motor cortex, the regions of the cerebral cortex i ...

. 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 Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). This occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells ( ...

, occurs mainly in the developing cortex before the organism has fully developed, and thus Eomesodermin/Tbr2 has been implicated in

neurodevelopment The development of the nervous system in humans, or neural development, or neurodevelopment involves the studies of embryology, developmental biology, and neuroscience. These describe the cellular and molecular mechanisms by which the complex ...

Tbr2 has been observed in a transcription factor cascade to enable to development of

glutamatergic Glutamatergic means "related to glutamate". A glutamatergic agent (or drug) is a chemical that directly modulates the excitatory amino acid (glutamate/aspartate) system in the body or brain. Examples include excitatory amino acid receptor agonist ...

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 subventricular zone (SVZ) is a region situated on the outside wall of each lateral ventricle of the vertebrate brain. It is present in both the embryonic and adult brain. In embryonic life, the SVZ refers to a secondary proliferative zon ...

. The IPCs then undergo symmetric division to produce

NeuroD NeuroD, also called Beta2, is a basic helix-loop-helix transcription factor expressed in certain parts of brain, beta pancreatic cells and enteroendocrine cells. It is involved in the differentiation of nervous system and development of pancreas. ...

expressing cells that can differentiate in TBR1 neurons. Similar mechanisms have been observed in both embryonic and adult neurogenesis. Tbr2 inactivation has also been tied to deficiencies in cortical neurogenesis further suggesting the importance of the cascade in activating and maintaining neuron production. 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

. This, may lead to the

microcephaly Microcephaly (from Neo-Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it m ...

(small head size due to improper brain development) seen in Eomesodermin/Tbr2 deficient mice. Eomesodermin/Tbr2 lacking mice have smaller upper

cortical layers The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. It is the largest site of neural integration in the central nervous system, and plays a key ...

and a smaller sub ventricular zone in the brain, and have an absence of a

mitral cell Mitral cells are neurons that are part of the olfactory system. They are located in the olfactory bulb in the mammalian central nervous system. They receive information from the axons of olfactory receptor neurons, forming synapses in neuropils ...

(neurons involved in the olfactory pathway) layer, with mitral cells instead being scattered about. Phenotypically, Eomesodermin/Tbr2 lacking mice show high

anger Anger, also known as wrath ( ; ) or rage (emotion), rage, is an intense emotional state involving a strong, uncomfortable and non-cooperative response to a perceived provocation, hurt, or threat. A person experiencing anger will often experie ...

levels and perform

infanticide Infanticide (or infant homicide) is the intentional killing of infants or offspring. Infanticide was a widespread practice throughout human history that was mainly used to dispose of unwanted children, its main purpose being the prevention of re ...

. Eomesodermin/Tbr2 lacking mice also seem to have problems with long

axon An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences) is a long, slender cellular extensions, projection of a nerve cell, or neuron, ...

connections. Axons are projections from neurons that connect with other cells in what is called a

synapse In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending o ...

and send

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

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 The commissural fibers or transverse fibers are axons that connect the two hemispheres of the brain. Huge numbers of commissural fibers make up the commissural tracts in the brain, the largest of which is the corpus callosum. In contrast to ...

s, which connect the two

hemispheres Hemisphere may refer to: In geometry * Hemisphere (geometry), a half of a sphere As half of Earth or any spherical astronomical object * A hemispheres of Earth, hemisphere of Earth ** Northern Hemisphere ** Southern Hemisphere ** Eastern Hemisphe ...

of the brain, and lack the

corpus callosum The corpus callosum (Latin for "tough body"), also callosal commissure, is a wide, thick nerve tract, consisting of a flat bundle of commissural fibers, beneath the cerebral cortex in the brain. The corpus callosum is only found in placental ...

, another region of the brain involved in hemisphere connections.

Role in adult development

There are locations within the brain that have been discovered to perform neurogenesis into

adult An adult is an animal that has reached full growth. The biological definition of the word means an animal reaching sexual maturity and thus capable of reproduction. In the human context, the term ''adult'' has meanings associated with social an ...

hood, including the ventricular zone. The

hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...

, which is involved in

memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembe ...

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 Long-term memory (LTM) is the stage of the Atkinson–Shiffrin memory model in which informative knowledge is held indefinitely. It is defined in contrast to sensory memory, the initial stage, and Short-term memory, short-term or working memory, ...

formation, which may relate to Eomesodermin/Tbr2's effects on the hippocampus.

Cardiac development

Early in development, Eomesodermin/Tbr2 controls early differentiation of the

cardiac The heart is a muscular organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrients to the tissu ...

mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical ...

. Lack of Eomesodermin/Tbr2 appears to be correlated with failure to differentiate into

cardiomyocytes Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall of ...

. Eomesodermin/Tbr2 controls the expression of cardiac specific genes Mesp1, Myl7,

Myl2 Myosin regulatory light chain 2, ventricular/cardiac muscle isoform (MLC-2) also known as the regulatory light chain of myosin (RLC) is a protein that in humans is encoded by the ''MYL2'' gene. This cardiac ventricular RLC isoform is distinct fro ...

, Myocardin, Nkx2.5 and

Mef2c Myocyte-specific enhancer factor 2C also known as MADS box transcription enhancer factor 2, polypeptide C is a protein that in humans is encoded by the ''MEF2C'' gene. MEF2C is a transcription factor in the Mef2 family. Genomics The gene is l ...

Immune response

Eomesodermin/Tbr2 is highly expressed in

CD8+ T cells A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pa ...

, but not

CD4+ T cells The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...

. CD4+ T cells are the helper

T cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their 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 Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

properties of CD8+ T cells. Lack of Eomesodermin/Tbr2, alongside T bet, another T box protein, caused CD8+ T cells to not penetrate

tumors A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

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.

Nervous system development

Neurogenesis

Role in adult development

Cardiac development

Immune response

See also

References

Further reading