Genomes and Genes
Gene Symbol: Tbr1
Description: T-box brain gene 1
Alias: T-box brain protein 1, T-brain-1, TBR-1, TES-56
- Batista Brito R, Rossignol E, Hjerling Leffler J, Denaxa M, Wegner M, Lefebvre V, et al. The cell-intrinsic requirement of Sox6 for cortical interneuron development. Neuron. 2009;63:466-81 pubmed publisher..It is, however, necessary for their normal positioning and maturation. As a consequence, the specific removal of Sox6 from this population results in a severe epileptic encephalopathy. ..
- Li S, Jin Z, Koirala S, Bu L, Xu L, Hynes R, et al. GPR56 regulates pial basement membrane integrity and cortical lamination. J Neurosci. 2008;28:5817-26 pubmed publisher..Furthermore, a putative ligand of GPR56 is localized in the marginal zone or overlying extracellular matrix. These observations provide compelling evidence that GPR56 functions in regulating pial BM integrity during cortical development...
- Harrison S, Nishinakamura R, Monaghan A. Sall1 regulates mitral cell development and olfactory nerve extension in the developing olfactory bulb. Cereb Cortex. 2008;18:1604-17 pubmed..In Sall1-mutant animals, these patterns of neurogenesis were disrupted. These findings suggest a role for Sall1 in regulating neuronal differentiation and maturation in developing neural structures. ..
- Hevner R, Hodge R, Daza R, Englund C. Transcription factors in glutamatergic neurogenesis: conserved programs in neocortex, cerebellum, and adult hippocampus. Neurosci Res. 2006;55:223-33 pubmed..Our work has focused on Pax6, Tbr2/Eomes, NeuroD, and Tbr1, which are expressed sequentially during the neurogenesis of pyramidal-projection neurons...
- Molyneaux B, Arlotta P, Hirata T, Hibi M, Macklis J. Fezl is required for the birth and specification of corticospinal motor neurons. Neuron. 2005;47:817-31 pubmed
- Bulfone A, Wang F, Hevner R, Anderson S, Cutforth T, Chen S, et al. An olfactory sensory map develops in the absence of normal projection neurons or GABAergic interneurons. Neuron. 1998;21:1273-82 pubmed..These observations suggest that the establishment of a topographic map is not dependent upon cues provided by, or synapse formation with, the major neuronal cell types in the olfactory bulb. ..
- Dominguez M, Ayoub A, Rakic P. POU-III transcription factors (Brn1, Brn2, and Oct6) influence neurogenesis, molecular identity, and migratory destination of upper-layer cells of the cerebral cortex. Cereb Cortex. 2013;23:2632-43 pubmed publisher..Finally, we demonstrate that Pou3fs influence multiple stages of neurogenesis by suppressing Notch effector Hes5, and promoting the expression of proneural transcription factors Tbr2 and Tbr1.
- Remedios R, Huilgol D, Saha B, Hari P, Bhatnagar L, Kowalczyk T, et al. A stream of cells migrating from the caudal telencephalon reveals a link between the amygdala and neocortex. Nat Neurosci. 2007;10:1141-50 pubmed..The CAS and the neocortex share mechanisms for specification (transcription factors Tbr1, Lhx2 and Emx1/2) and migration (reelin and Cdk5)...
- Hevner R, Shi L, Justice N, Hsueh Y, Sheng M, Smiga S, et al. Tbr1 regulates differentiation of the preplate and layer 6. Neuron. 2001;29:353-66 pubmed..b>Tbr1 is a putative transcription factor that is highly expressed in glutamatergic early-born cortical neurons...
- Shu T, Butz K, Plachez C, Gronostajski R, Richards L. Abnormal development of forebrain midline glia and commissural projections in Nfia knock-out mice. J Neurosci. 2003;23:203-12 pubmed..2001) appear relatively normal. These results support an essential role for midline glia in callosum development and a role for Nfia in the formation of midline glial structures. ..
- Meechan D, Tucker E, Maynard T, LaMantia A. Diminished dosage of 22q11 genes disrupts neurogenesis and cortical development in a mouse model of 22q11 deletion/DiGeorge syndrome. Proc Natl Acad Sci U S A. 2009;106:16434-45 pubmed publisher..Such developmental disruption may alter cortical circuitry and establish vulnerability for developmental disorders, including schizophrenia and autism. ..
- Puelles L, Kuwana E, Puelles E, Bulfone A, Shimamura K, Keleher J, et al. Pallial and subpallial derivatives in the embryonic chick and mouse telencephalon, traced by the expression of the genes Dlx-2, Emx-1, Nkx-2.1, Pax-6, and Tbr-1. J Comp Neurol. 2000;424:409-38 pubmed..These may underlie similar histogenetic specification processes and field homologies, including some comparable connectivity patterns. ..
- Way S, McKenna J, Mietzsch U, Reith R, Wu H, Gambello M. Loss of Tsc2 in radial glia models the brain pathology of tuberous sclerosis complex in the mouse. Hum Mol Genet. 2009;18:1252-65 pubmed publisher..loss of Tsc2 increased the subventricular Tbr2-positive basal cell progenitor pool at the expense of early born Tbr1-positive post-mitotic neurons...
- Kwan K, Lam M, Krsnik Z, Kawasawa Y, Lefebvre V, Sestan N. SOX5 postmitotically regulates migration, postmigratory differentiation, and projections of subplate and deep-layer neocortical neurons. Proc Natl Acad Sci U S A. 2008;105:16021-6 pubmed publisher..Thus, SOX5 postmitotically regulates the migration, postmigratory differentiation, and subcortical projections of subplate and deep-layer neurons. ..
- Carney R, Cocas L, Hirata T, Mansfield K, Corbin J. Differential regulation of telencephalic pallial-subpallial boundary patterning by Pax6 and Gsh2. Cereb Cortex. 2009;19:745-59 pubmed publisher..Thus, in addition to their well-characterized cross-repressive roles in dorsal/ventral patterning our analyses reveal important novel functions of Gsh2 and Pax6 in the regulation of PSB progenitor pool specification and patterning. ..
- Komada M, Saitsu H, Kinboshi M, Miura T, Shiota K, Ishibashi M. Hedgehog signaling is involved in development of the neocortex. Development. 2008;135:2717-27 pubmed publisher..Reduced Shh immunoreactivity in mutant dorsal telencephalons supports the above phenotypes. Our data indicate that Shh signaling plays an important role in development of the neocortex. ..
- Faedo A, Ficara F, Ghiani M, Aiuti A, Rubenstein J, Bulfone A. Developmental expression of the T-box transcription factor T-bet/Tbx21 during mouse embryogenesis. Mech Dev. 2002;116:157-60 pubmed..15 (1999) 154). We have identified and characterized the expression pattern of a new member of the Tbr1 subfamily of T-box genes; this gene has been recently named T-bet/Tbx21 (Genomics 70 (2000) 41; Cell 17 (2000) 655; ..
- Konno D, Shioi G, Shitamukai A, Mori A, Kiyonari H, Miyata T, et al. Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis. Nat Cell Biol. 2008;10:93-101 pubmed..Our results suggest that planar mitosis ensures the self-renewal of neuroepithelial progenitors by one daughter inheriting both apical and basal compartments during neurogenesis. ..
- Depaepe V, Suarez Gonzalez N, Dufour A, Passante L, Gorski J, Jones K, et al. Ephrin signalling controls brain size by regulating apoptosis of neural progenitors. Nature. 2005;435:1244-50 pubmed..Together, these results identify ephrin/Eph signalling as a physiological trigger for apoptosis that can alter brain size and shape by regulating the number of neural progenitors. ..
- Chenn A, Walsh C. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science. 2002;297:365-9 pubmed
- Schuurmans C, Armant O, Nieto M, Stenman J, Britz O, Klenin N, et al. Sequential phases of cortical specification involve Neurogenin-dependent and -independent pathways. EMBO J. 2004;23:2892-902 pubmed..Our study thus reveals an unanticipated heterogeneity in the genetic mechanisms specifying the identity of neocortical projection neurons. ..
- Luo R, Jeong S, Jin Z, Strokes N, Li S, Piao X. G protein-coupled receptor 56 and collagen III, a receptor-ligand pair, regulates cortical development and lamination. Proc Natl Acad Sci U S A. 2011;108:12925-30 pubmed publisher..Thus, collagen III regulates the proper lamination of the cerebral cortex by acting as the major ligand of GPR56 in the developing brain. ..
- Armentano M, Chou S, Tomassy G, Leingartner A, O Leary D, Studer M. COUP-TFI regulates the balance of cortical patterning between frontal/motor and sensory areas. Nat Neurosci. 2007;10:1277-86 pubmed..We conclude that COUP-TFI is required for balancing patterning of neocortex into frontal/motor and sensory areas by acting in its expression domain to repress frontal/motor area identities and to specify sensory area identities. ..
- Westerlund N, Zdrojewska J, Padzik A, Komulainen E, Björkblom B, Rannikko E, et al. Phosphorylation of SCG10/stathmin-2 determines multipolar stage exit and neuronal migration rate. Nat Neurosci. 2011;14:305-13 pubmed publisher..These findings indicate that the phosphorylation of SCG10 by JNK1 is a fundamental mechanism that governs the transition from the multipolar stage and the rate of neuronal cell movement during cortical development. ..
- Vergaño Vera E, Yusta Boyo M, De Castro F, Bernad A, de Pablo F, Vicario Abejón C. Generation of GABAergic and dopaminergic interneurons from endogenous embryonic olfactory bulb precursor cells. Development. 2006;133:4367-79 pubmed..These findings suggest that, in addition to receiving interneurons from the LGE, the embryonic OB contains molecularly distinct local precursor cells that generate mature GABAergic and dopaminergic neurons. ..
- Feng Y, Walsh C. Mitotic spindle regulation by Nde1 controls cerebral cortical size. Neuron. 2004;44:279-93 pubmed..Our data show that mitotic spindle function and orientation are essential for normal development of mammalian cerebral cortex. ..
- Stevens H, Smith K, Maragnoli M, Fagel D, Borok E, Shanabrough M, et al. Fgfr2 is required for the development of the medial prefrontal cortex and its connections with limbic circuits. J Neurosci. 2010;30:5590-602 pubmed publisher..These data demonstrate that FGFR2 signaling expands the number of excitatory neurons in the mPFC and secondarily influences target neurons in subcortical stations of the limbic system. ..
- Storm E, Garel S, Borello U, Hebert J, Martinez S, McConnell S, et al. Dose-dependent functions of Fgf8 in regulating telencephalic patterning centers. Development. 2006;133:1831-44 pubmed..These data suggest that Fgf8 functions to coordinate multiple patterning centers, and that modifications in the relative strength of FGF signaling can have profound effects on the relative size and nature of telencephalic subdivisions. ..
- Fink A, Englund C, Daza R, Pham D, Lau C, Nivison M, et al. Development of the deep cerebellar nuclei: transcription factors and cell migration from the rhombic lip. J Neurosci. 2006;26:3066-76 pubmed..The rhombic lip-derived cells express transcription factors Pax6, Tbr2, and Tbr1 sequentially as they enter the NTZ...
- Lizarraga S, Margossian S, Harris M, Campagna D, Han A, Blevins S, et al. Cdk5rap2 regulates centrosome function and chromosome segregation in neuronal progenitors. Development. 2010;137:1907-17 pubmed publisher..Our findings suggest that the reduction in brain size observed in humans with mutations in CDK5RAP2 is associated with impaired centrosomal function and with changes in mitotic spindle orientation during progenitor proliferation. ..
- Englund C, Fink A, Lau C, Pham D, Daza R, Bulfone A, et al. Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex. J Neurosci. 2005;25:247-51 pubmed..from intermediate progenitor cell to postmitotic neuron is marked by downregulation of Tbr2 and upregulation of Tbr1, another T-domain transcription factor...
- Wang V, Rose M, Zoghbi H. Math1 expression redefines the rhombic lip derivatives and reveals novel lineages within the brainstem and cerebellum. Neuron. 2005;48:31-43 pubmed
- Sessa A, Mao C, Hadjantonakis A, Klein W, Broccoli V. Tbr2 directs conversion of radial glia into basal precursors and guides neuronal amplification by indirect neurogenesis in the developing neocortex. Neuron. 2008;60:56-69 pubmed publisher..Together, these findings identify Tbr2 as a critical factor for the specification of IPCs during corticogenesis. ..
- García Moreno F, Pedraza M, Di Giovannantonio L, Di Salvio M, López Mascaraque L, Simeone A, et al. A neuronal migratory pathway crossing from diencephalon to telencephalon populates amygdala nuclei. Nat Neurosci. 2010;13:680-9 pubmed publisher..The diencephalic transcription factor OTP was necessary for this migratory behavior. ..
- Faedo A, Tomassy G, Ruan Y, Teichmann H, Krauss S, Pleasure S, et al. COUP-TFI coordinates cortical patterning, neurogenesis, and laminar fate and modulates MAPK/ERK, AKT, and beta-catenin signaling. Cereb Cortex. 2008;18:2117-31 pubmed publisher..We suggest that COUP-TFI controls these processes by repressing Mapk/Erk, Akt, and beta-catenin signaling. ..
- Barnes A, Lilley B, Pan Y, Plummer L, Powell A, Raines A, et al. LKB1 and SAD kinases define a pathway required for the polarization of cortical neurons. Cell. 2007;129:549-63 pubmed..Thus, we provide evidence in vivo and in vitro for a multikinase pathway that links extracellular signals to the intracellular machinery required for axon specification. ..
- Barry G, Piper M, Lindwall C, Moldrich R, Mason S, Little E, et al. Specific glial populations regulate hippocampal morphogenesis. J Neurosci. 2008;28:12328-40 pubmed publisher..These data demonstrate a role for Nfib in hippocampal fissure and dentate gyrus formation, and that distinct glial bundles are critical for correct hippocampal morphogenesis. ..
- Seah C, Levy M, Jiang Y, Mokhtarzada S, Higgs D, Gibbons R, et al. Neuronal death resulting from targeted disruption of the Snf2 protein ATRX is mediated by p53. J Neurosci. 2008;28:12570-80 pubmed publisher..Together, these findings show that ATRX deficiency leads to p53-dependent neuronal apoptosis which is responsible for some but not all of the phenotypic consequences of ATRX deficiency in the forebrain. ..
- Kolk S, Whitman M, Yun M, Shete P, Donoghue M. A unique subpopulation of Tbr1-expressing deep layer neurons in the developing cerebral cortex. Mol Cell Neurosci. 2006;32:200-14 pubmed..Here, we provide a tool to illuminate a unique subset of SP and deep CP neurons: expression of a Tbrain-1 (Tbr1)-driven transgene...
- Radakovits R, Barros C, Belvindrah R, Patton B, Muller U. Regulation of radial glial survival by signals from the meninges. J Neurosci. 2009;29:7694-705 pubmed publisher..Our findings demonstrate that attachment of RGC processes at the meninges is important for RGC survival and the control of cortical size. ..
- Pulvers J, Huttner W. Brca1 is required for embryonic development of the mouse cerebral cortex to normal size by preventing apoptosis of early neural progenitors. Development. 2009;136:1859-68 pubmed publisher..Our results show that Brca1 is required for the cerebral cortex to develop to normal size by preventing the apoptosis of early cortical progenitors and their immediate progeny. ..
- Xu Q, Wonders C, Anderson S. Sonic hedgehog maintains the identity of cortical interneuron progenitors in the ventral telencephalon. Development. 2005;132:4987-98 pubmed..These results combine in vitro and ex vivo analyses to link embryonic abnormalities in Shh signaling to postnatal alterations in cortical interneuron composition. ..
- Cocas L, Miyoshi G, Carney R, Sousa V, Hirata T, Jones K, et al. Emx1-lineage progenitors differentially contribute to neural diversity in the striatum and amygdala. J Neurosci. 2009;29:15933-46 pubmed publisher..Thus, both the timing of neurogenesis and differential combinatorial gene expression appear to be key determinants of striatal versus amygdala fate decisions of Emx1-lineage cells. ..
- Fode C, Ma Q, Casarosa S, Ang S, Anderson D, Guillemot F. A role for neural determination genes in specifying the dorsoventral identity of telencephalic neurons. Genes Dev. 2000;14:67-80 pubmed
- Postiglione M, Jüschke C, Xie Y, Haas G, Charalambous C, Knoblich J. Mouse inscuteable induces apical-basal spindle orientation to facilitate intermediate progenitor generation in the developing neocortex. Neuron. 2011;72:269-84 pubmed publisher..Our results indicate that the orientation of progenitor cell divisions is important for correct lineage specification in the developing mammalian brain. ..
- Bulfone A, Smiga S, Shimamura K, Peterson A, Puelles L, Rubenstein J. T-brain-1: a homolog of Brachyury whose expression defines molecularly distinct domains within the cerebral cortex. Neuron. 1995;15:63-78 pubmed..Tbr-1 expression is analyzed in the context of the prosomeric model. Topological maps are proposed for the organization of the dorsal telencephalon. ..
- Yokota Y, Kim W, Chen Y, Wang X, Stanco A, Komuro Y, et al. The adenomatous polyposis coli protein is an essential regulator of radial glial polarity and construction of the cerebral cortex. Neuron. 2009;61:42-56 pubmed publisher..Thus, APC is an essential regulator of radial glial polarity and is critical for the construction of cerebral cortex in mammals. ..
- Franco S, Gil Sanz C, Martinez Garay I, Espinosa A, Harkins Perry S, Ramos C, et al. Fate-restricted neural progenitors in the mammalian cerebral cortex. Science. 2012;337:746-9 pubmed publisher..Because upper cortical layers were expanded during primate evolution, amplification of this RGC pool may have facilitated human brain evolution. ..
- Lehtinen M, Zappaterra M, Chen X, Yang Y, Hill A, Lun M, et al. The cerebrospinal fluid provides a proliferative niche for neural progenitor cells. Neuron. 2011;69:893-905 pubmed publisher..The temporal control of CSF composition may have critical relevance to normal development and neuropathological conditions...
- Kawase Koga Y, Otaegi G, Sun T. Different timings of Dicer deletion affect neurogenesis and gliogenesis in the developing mouse central nervous system. Dev Dyn. 2009;238:2800-12 pubmed publisher..Our studies of different timings of Dicer deletion demonstrate the importance of the Dicer-mediated microRNA pathway in regulating distinct phases of neurogenesis and gliogenesis during the CNS development. ..
- Hebert J, Hayhurst M, Marks M, Kulessa H, Hogan B, McConnell S. BMP ligands act redundantly to pattern the dorsal telencephalic midline. Genesis. 2003;35:214-9 pubmed
- Britanova O, de Juan Romero C, Cheung A, Kwan K, Schwark M, Gyorgy A, et al. Satb2 is a postmitotic determinant for upper-layer neuron specification in the neocortex. Neuron. 2008;57:378-92 pubmed publisher..Satb2 therefore is required for the initiation of the UL1-specific genetic program and for the inactivation of DL- and UL2-specific genes. ..
- Kohwi M, Petryniak M, Long J, Ekker M, Obata K, Yanagawa Y, et al. A subpopulation of olfactory bulb GABAergic interneurons is derived from Emx1- and Dlx5/6-expressing progenitors. J Neurosci. 2007;27:6878-91 pubmed..Our results suggest that some OB interneurons are derived from progenitors outside the LGE and that precursors expressing what has classically been considered a pallial transcription factor generate GABAergic interneurons. ..
- Zarbalis K, Siegenthaler J, Choe Y, May S, Peterson A, Pleasure S. Cortical dysplasia and skull defects in mice with a Foxc1 allele reveal the role of meningeal differentiation in regulating cortical development. Proc Natl Acad Sci U S A. 2007;104:14002-7 pubmed..Furthermore, we provide evidence that defects in meningeal differentiation can lead to severe cortical dysplasia. ..