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 HIF1A
Homo sapiens
 Pax6
Mus musculus
 PAX6
Homo sapiens
 Snai2
Mus musculus
 PPARA
Homo sapiens
 Ppara
Mus musculus
 Thrb
Mus musculus
 SNAI2
Homo sapiens
 Tbr1
Mus musculus
 SIX3
Homo sapiens
Transcription Factor Encyclopedia  BETA
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Overview

TBR1 (T-Brain-1), EOMES (Eomesodermin), and TBX21 together form the TBR1 subfamily of T-box genes in vertebrates (see review by Naiche et al., 2005, in Papers tab)[1]. EOMES is also known as TBR2; TBX21 is also known as T-BET. T-box genes are also found in invertebrate animals, but not outside the animal kingdom. However, TBR1 subfamily genes are not present in Drosophila or C. elegans.

Like other members of the T-box family (17 in mammals), TBR1 subfamily genes are mainly important for development and differentiation of specific cell types in various organs. Expression mapping and targeted mutations in mice have revealed both overlapping and non-overlapping roles for Tbr1 subfamily genes in the development of brain, eye, immune system, mesoderm, and placenta. Examples of specific functions mediated by TBR1 family genes include the following. Eomes and Tbr1 implement a program of glutamatergic neuronal differentiation in developing mouse brain (Hevner et al., Neurosci. Res., 2006)[2]. Tbx21 activates the program of Th1 differentiation in T-cells, and represses Th2 fate (Szabo et al., Cell, 2000)[3]. Indeed, Tbx21 and Eomes are critical regulators in a number of immune cell types (Glimcher et al., Nat. Rev. Immunol., 2004)[4].

In contrast to the fascinating phenotypes in mice, much less is known about TBR1 subfamily functions in humans. Only EOMES has been linked to a specific human disorder, severely affecting the brain (see Baala et al., 2007, in Papers tab)[5]. Frogs and zebrafish have also been important model systems for studying these genes, which have been identified in many vertebrates. Insights into the evolution of the TBR1 subfamily have come from studies in Amphioxus, where a single orthologous gene is expressed (Horton and Gibson-Brown, J. Exp. Zool., 2002)[6].

References
  1. Naiche LA et al. T-box genes in vertebrate development. Annu. Rev. Genet., 39:219-39. (PMID 16285859)
  2. Hevner RF et al. Transcription factors in glutamatergic neurogenesis: conserved programs in neocortex, cerebellum, and adult hippocampus. Neurosci. Res., 55(3):223-33. (PMID 16621079)
  3. Szabo SJ et al. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell, 100(6):655-69. (PMID 10761931)
  1. Glimcher LH et al. Recent developments in the transcriptional regulation of cytolytic effector cells. Nat. Rev. Immunol., 4(11):900-11. (PMID 15516969)
  2. Baala L et al. Homozygous silencing of T-box transcription factor EOMES leads to microcephaly with polymicrogyria and corpus callosum agenesis. Nat. Genet., 39(4):454-6. (PMID 17353897)
  3. Horton AC and Gibson-Brown JJ. Evolution of developmental functions by the Eomesodermin, T-brain-1, Tbx21 subfamily of T-box genes: insights from amphioxus. J. Exp. Zool., 294(2):112-21. (PMID 12210112)
Figures
FIGURE 1 Expression of Tbr1, Eomes, and Tbx21 in embryonic mouse brain.
All three TBR1 subfamily genes are expressed in the developing olfactory bulb. In addition, Tbr1 and Eomes are expressed in the developing cerebral cortex, in the glutamatergic neuron lineage. Eomes is expressed by intermediate neuronal progenitors, while Tbr1 is expressed by postmitotic cortical neurons[1]. Tbr1 and Eomes are furthermore important for glutamatergic neurogenesis in the developing cerebellum[2][3]. Also shown is Tbx20, expressed in some hindbrain neurons[4].
References
  1. Englund C et al. Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex. J. Neurosci., 25(1):247-51. (PMID 15634788)
  2. Englund C et al. Unipolar brush cells of the cerebellum are produced in the rhombic lip and migrate through developing white matter. J. Neurosci., 26(36):9184-95. (PMID 16957075)
  1. Fink AJ et al. Development of the deep cerebellar nuclei: transcription factors and cell migration from the rhombic lip. J. Neurosci., 26(11):3066-76. (PMID 16540585)
  2. Song MR et al. T-Box transcription factor Tbx20 regulates a genetic program for cranial motor neuron cell body migration. Development, 133(24):4945-55. (PMID 17119020)
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