Genomes and Genes
Gene Symbol: Gbx2
Description: gastrulation brain homeobox 2
Alias: D130058E05Rik, Gbx-2, MMoxA, Stra7, homeobox protein GBX-2, gastrulation and brain-specific homeobox protein 2, stimulated by retinoic acid gene 7 protein
- Vue T, Aaker J, Taniguchi A, Kazemzadeh C, Skidmore J, Martin D, et al. Characterization of progenitor domains in the developing mouse thalamus. J Comp Neurol. 2007;505:73-91 pubmed..These results establish the molecular heterogeneity within the progenitor cells of the thalamus, and suggest that such heterogeneity contributes to the specification of thalamic nuclei. ..
- Hashimoto Torii K, Motoyama J, Hui C, Kuroiwa A, Nakafuku M, Shimamura K. Differential activities of Sonic hedgehog mediated by Gli transcription factors define distinct neuronal subtypes in the dorsal thalamus. Mech Dev. 2003;120:1097-111 pubmed..As a first step to this end, we focused on two transcription factors Sox14 and Gbx2 that are expressed in the specific brain nuclei in the chick DT...
- Inoue F, Kurokawa D, Takahashi M, Aizawa S. Gbx2 directly restricts Otx2 expression to forebrain and midbrain, competing with class III POU factors. Mol Cell Biol. 2012;32:2618-27 pubmed publisherOtx2 plays essential roles in rostral brain development, and its counteraction with Gbx2 has been suggested to determine the midbrain-hindbrain boundary (MHB) in vertebrates...
- Kurokawa D, Takasaki N, Kiyonari H, Nakayama R, Kimura Yoshida C, Matsuo I, et al. Regulation of Otx2 expression and its functions in mouse epiblast and anterior neuroectoderm. Development. 2004;131:3307-17 pubmed..The AN enhancer region is conserved among mouse, human and Xenopus; moreover, the counterpart region in Xenopus exhibited an enhancer activity in mouse anterior neuroectoderm. ..
- Bramblett D, Copeland N, Jenkins N, Tsai M. BHLHB4 is a bHLH transcriptional regulator in pancreas and brain that marks the dimesencephalic boundary. Genomics. 2002;79:402-12 pubmed..Together, these data suggest that BHLHB4 may modulate the expression of genes required for the differentiation and/or maintenance of pancreatic and neuronal cell types. ..
- Ye W, Bouchard M, Stone D, Liu X, Vella F, Lee J, et al. Distinct regulators control the expression of the mid-hindbrain organizer signal FGF8. Nat Neurosci. 2001;4:1175-81 pubmed..A network of transcription and secreted factors, including En1, Otx2, Gbx2, Grg4 and Wnt1&4, that is established independently of Pax2, further refines the expression domain and level of ..
- Boyl P, Signore M, Acampora D, Martinez Barbera J, Ilengo C, Annino A, et al. Forebrain and midbrain development requires epiblast-restricted Otx2 translational control mediated by its 3' UTR. Development. 2001;128:2989-3000 pubmed..This leads us to hypothesise that this control might have important evolutionary implications. ..
- Prakash N, Brodski C, Naserke T, Puelles E, Gogoi R, Hall A, et al. A Wnt1-regulated genetic network controls the identity and fate of midbrain-dopaminergic progenitors in vivo. Development. 2006;133:89-98 pubmed..They also suggest the Wnt1-controlled signaling pathway as a promising target for new therapeutic strategies in the treatment of Parkinson's disease. ..
- Acampora D, Boyl P, Signore M, Martinez Barbera J, Ilengo C, Puelles E, et al. OTD/OTX2 functional equivalence depends on 5' and 3' UTR-mediated control of Otx2 mRNA for nucleo-cytoplasmic export and epiblast-restricted translation. Development. 2001;128:4801-13 pubmed..These data provide novel in vivo evidence supporting the concept that during evolution pre-existing gene functions have been recruited into new developmental pathways by modifying their regulatory control. ..
- Randall V, McCue K, Roberts C, Kyriakopoulou V, Beddow S, Barrett A, et al. Great vessel development requires biallelic expression of Chd7 and Tbx1 in pharyngeal ectoderm in mice. J Clin Invest. 2009;119:3301-10 pubmed publisher..We could not rescue PAA morphogenesis by restoring neural crest Chd7 expression. Rather, biallelic expression of Chd7 and Tbx1 in the pharyngeal ectoderm was required for normal PAA development...
- Grindley J, Hargett L, Hill R, Ross A, Hogan B. Disruption of PAX6 function in mice homozygous for the Pax6Sey-1Neu mutation produces abnormalities in the early development and regionalization of the diencephalon. Mech Dev. 1997;64:111-26 pubmed..Thus, PAX6 is essential for the normal development and regionalization of the diencephalon. ..
- Bouillet P, Chazaud C, Oulad Abdelghani M, Dolle P, Chambon P. Sequence and expression pattern of the Stra7 (Gbx-2) homeobox-containing gene induced by retinoic acid in P19 embryonal carcinoma cells. Dev Dyn. 1995;204:372-82 pubmed..to the full-length form of the 77 bp homeodomain-encoding cDNA fragment which was previously cloned and termed MMoxA or Gbx-2...
- Hevner R, Miyashita Lin E, Rubenstein J. Cortical and thalamic axon pathfinding defects in Tbr1, Gbx2, and Pax6 mutant mice: evidence that cortical and thalamic axons interact and guide each other. J Comp Neurol. 2002;447:8-17 pubmed..mice with mutations of transcription factor genes expressed specifically in the cortex (Tbr1), the dorsal thalamus (Gbx2), or both (Pax6)...
- Li K, Zhang J, Li J. Gbx2 plays an essential but transient role in the formation of thalamic nuclei. PLoS ONE. 2012;7:e47111 pubmed publisher..Homeodomain transcription factor Gbx2 is specifically expressed in the developing thalamus...
- Seibt J, Schuurmans C, Gradwhol G, Dehay C, Vanderhaeghen P, Guillemot F, et al. Neurogenin2 specifies the connectivity of thalamic neurons by controlling axon responsiveness to intermediate target cues. Neuron. 2003;39:439-52 pubmed..Our results thus demonstrate that in parallel to their well-documented proneural function, bHLH transcription factors also contribute to the specification of neuronal connectivity in the mammalian brain. ..
- Nakagawa Y, O Leary D. Combinatorial expression patterns of LIM-homeodomain and other regulatory genes parcellate developing thalamus. J Neurosci. 2001;21:2711-25 pubmed..which include five LIM-homeodomain transcription factors (Isl1, Lhx1, Lhx2, Lhx5, and Lhx9) and three other genes (Gbx2, Ngn2, and Pax6), that are differentially expressed in dTh and vTh of early postnatal mice in distinct but ..
- Li J, Joyner A. Otx2 and Gbx2 are required for refinement and not induction of mid-hindbrain gene expression. Development. 2001;128:4979-91 pubmedOtx2 and Gbx2 are among the earliest genes expressed in the neuroectoderm, dividing it into anterior and posterior domains with a common border that marks the mid-hindbrain junction...
- Chatterjee M, Li K, Chen L, Maisano X, Guo Q, Gan L, et al. Gbx2 regulates thalamocortical axon guidance by modifying the LIM and Robo codes. Development. 2012;139:4633-43 pubmed publisher..The homeodomain transcription factor Gbx2 is essential for TCA development, as loss of Gbx2 abolishes TCAs in mice...
- Acampora D, Avantaggiato V, Tuorto F, Briata P, Corte G, Simeone A. Visceral endoderm-restricted translation of Otx1 mediates recovery of Otx2 requirements for specification of anterior neural plate and normal gastrulation. Development. 1998;125:5091-104 pubmed..Moreover, our data lead us to hypothesize that the differential post-transcriptional control existing between VE and epiblast cells may potentially contribute to fundamental regulatory mechanisms required for head specification. ..
- Acampora D, Avantaggiato V, Tuorto F, Simeone A. Genetic control of brain morphogenesis through Otx gene dosage requirement. Development. 1997;124:3639-50 pubmed
- Wassarman K, Lewandoski M, Campbell K, Joyner A, Rubenstein J, Martinez S, et al. Specification of the anterior hindbrain and establishment of a normal mid/hindbrain organizer is dependent on Gbx2 gene function. Development. 1997;124:2923-34 pubmedAnalysis of mouse embryos homozygous for a loss-of-function allele of Gbx2 demonstrates that this homeobox gene is required for normal development of the mid/hindbrain region...
- Bulfone A, Puelles L, Porteus M, Frohman M, Martin G, Rubenstein J. Spatially restricted expression of Dlx-1, Dlx-2 (Tes-1), Gbx-2, and Wnt-3 in the embryonic day 12.5 mouse forebrain defines potential transverse and longitudinal segmental boundaries. J Neurosci. 1993;13:3155-72 pubmed..These findings are consistent with neuromeric theories of forebrain development, and based upon them we suggest a model for forebrain segmentation. ..
- Bonnin A, Torii M, Wang L, Rakic P, Levitt P. Serotonin modulates the response of embryonic thalamocortical axons to netrin-1. Nat Neurosci. 2007;10:588-97 pubmed..These data demonstrate that serotonergic signaling has a previously unrecognized role in the modulation of axonal responsiveness to a classic guidance cue. ..
- Basson M, Echevarria D, Ahn C, Sudarov A, Joyner A, Mason I, et al. Specific regions within the embryonic midbrain and cerebellum require different levels of FGF signaling during development. Development. 2008;135:889-98 pubmed publisher..We suggest a molecular explanation for this phenomenon by providing evidence that FGF signaling functions to inhibit the BMP signaling that promotes roof plate development. ..
- Chen L, Guo Q, Li J. Transcription factor Gbx2 acts cell-nonautonomously to regulate the formation of lineage-restriction boundaries of the thalamus. Development. 2009;136:1317-26 pubmed publisher..We demonstrate here that Gbx2-expressing cells in mouse diencephalon contribute to the entire thalamic nuclear complex...
- Chi C, Martinez S, Wurst W, Martin G. The isthmic organizer signal FGF8 is required for cell survival in the prospective midbrain and cerebellum. Development. 2003;130:2633-44 pubmed..75). This resulted in a failure to maintain expression of Wnt1 as well as Fgf17, Fgf18, and Gbx2 in the mes/met at early somite stages, and in the absence of the midbrain and cerebellum at E17.5...
- Trokovic R, Trokovic N, Hernesniemi S, Pirvola U, Vogt Weisenhorn D, Rossant J, et al. FGFR1 is independently required in both developing mid- and hindbrain for sustained response to isthmic signals. EMBO J. 2003;22:1811-23 pubmed..In addition, FGFR1 appears to modify cell adhesion properties critical for maintaining a coherent organizing center. This may be achieved by regulating expression of specific cell-adhesion molecules at the midbrain-hindbrain border. ..
- Garel S, Yun K, Grosschedl R, Rubenstein J. The early topography of thalamocortical projections is shifted in Ebf1 and Dlx1/2 mutant mice. Development. 2002;129:5621-34 pubmed..These observations suggest that the topography of thalamocortical projections is not strictly determined by cues located within the neocortex and may be regulated by the relative positioning of thalamic axons inside the basal ganglia. ..
- Li J, Lao Z, Joyner A. Changing requirements for Gbx2 in development of the cerebellum and maintenance of the mid/hindbrain organizer. Neuron. 2002;36:31-43 pubmedWe examined whether Gbx2 is required after embryonic day 9 (E9) to repress Otx2 in the cerebellar anlage and position the midbrain/hindbrain organizer...
- Tian E, Kimura C, Takeda N, Aizawa S, Matsuo I. Otx2 is required to respond to signals from anterior neural ridge for forebrain specification. Dev Biol. 2002;242:204-23 pubmed..These results further suggest that Otx2 dosage may be crucial in the neural plate with respect to response to inductive signals primarily from the ANR for forebrain specification. ..
- Sakurai Y, Kurokawa D, Kiyonari H, Kajikawa E, Suda Y, Aizawa S. Otx2 and Otx1 protect diencephalon and mesencephalon from caudalization into metencephalon during early brain regionalization. Dev Biol. 2010;347:392-403 pubmed publisher..In contrast, the medial pallium requires Otx1 and Otx2 for its development later than E9.5, and the Otx2 expression in diencepalon and mesencephalon later than E9.5 is also directed by an enhancer other than FM1 and FM2 enhancers. ..
- Chen L, Chatterjee M, Li J. The mouse homeobox gene Gbx2 is required for the development of cholinergic interneurons in the striatum. J Neurosci. 2010;30:14824-34 pubmed publisher..fate mapping, here we examined the developmental fate of cells that express the homeodomain transcription factor Gbx2 in the MGE...
- Yu T, Yaguchi Y, Echevarria D, Martinez S, Basson M. Sprouty genes prevent excessive FGF signalling in multiple cell types throughout development of the cerebellum. Development. 2011;138:2957-68 pubmed publisher..Taken together, our data demonstrate that FGF signalling levels have to be tightly controlled throughout cerebellar development in order to maintain the normal development of multiple cell types. ..
- Szabó N, Zhao T, Zhou X, Alvarez Bolado G. The role of Sonic hedgehog of neural origin in thalamic differentiation in the mouse. J Neurosci. 2009;29:2453-66 pubmed publisher..We show that the transcription factor Gbx2, required for thalamic development downstream Shh, is expressed in our mutant in a restricted thalamic region and ..
- Panhuysen M, Vogt Weisenhorn D, Blanquet V, Brodski C, Heinzmann U, Beisker W, et al. Effects of Wnt1 signaling on proliferation in the developing mid-/hindbrain region. Mol Cell Neurosci. 2004;26:101-11 pubmed..We suggest that Wnt1 acts as a regulator of proliferation of specific precursor populations in the developing mid-/hindbrain region and is only secondarily involved in maintenance of the mid-/hindbrain organizer. ..
- Yang J, Brown A, Ellisor D, Paul E, Hagan N, Zervas M. Dynamic temporal requirement of Wnt1 in midbrain dopamine neuron development. Development. 2013;140:1342-52 pubmed publisher..Collectively, our analyses resolve the spatial and temporal function of Wnt1 in Mb and Cb patterning and in MbDA neuron development in vivo. ..
- Zhou C, Pinson K, Pleasure S. Severe defects in dorsal thalamic development in low-density lipoprotein receptor-related protein-6 mutants. J Neurosci. 2004;24:7632-9 pubmed..This study provides compelling in vivo evidence that thalamic development requires normal activity of the LRP6-mediated canonical Wnt signaling pathway. ..
- Lilleväli K, Haugas M, Matilainen T, Pussinen C, Karis A, Salminen M. Gata3 is required for early morphogenesis and Fgf10 expression during otic development. Mech Dev. 2006;123:415-29 pubmed..Inactivation of Gata3 leads also to a loss of Fgf10 expression in otic epithelium and auditory ganglion demonstrating that Gata3 is an important regulator of Fgf-signalling during otic development. ..
- Marcos Mondejar P, Peregrin S, Li J, Carlsson L, Tole S, Lopez Bendito G. The lhx2 transcription factor controls thalamocortical axonal guidance by specific regulation of robo1 and robo2 receptors. J Neurosci. 2012;32:4372-85 pubmed publisher..By regulating axon guidance receptors, such as Robo1 and Robo2, Lhx2 differentially regulates the axon guidance program of distinct populations of thalamic neurons, thus enabling the establishment of specific neural connections. ..
- Chatterjee M, Guo Q, Weber S, Scholpp S, LI J. Pax6 regulates the formation of the habenular nuclei by controlling the temporospatial expression of Shh in the diencephalon in vertebrates. BMC Biol. 2014;12:13 pubmed publisher..Furthermore, Shh mediates Pax6 function in regulating the partition of the p2 domain into the epithalamus and thalamus. ..
- Acampora D, Annino A, Puelles E, Alfano I, Tuorto F, Simeone A. OTX1 compensates for OTX2 requirement in regionalisation of anterior neuroectoderm. Gene Expr Patterns. 2003;3:497-501 pubmed..Patterning and regionalisation of forebrain and midbrain were unaffected as revealed by the expression of diagnostic genes which are highly sensitive to reduction of OTX proteins, such as Fgf8, Pax2 and Gbx2.
- Mori T, Yuxing Z, Takaki H, Takeuchi M, Iseki K, Hagino S, et al. The LIM homeobox gene, L3/Lhx8, is necessary for proper development of basal forebrain cholinergic neurons. Eur J Neurosci. 2004;19:3129-41 pubmed..Neurotransmitter phenotypes other than cholinergic in the basal forebrain appeared intact. From these results, we suggested that L3/Lhx8 has a pivotal and specific role in the development and/or maintenance of BFCNs. ..
- Cheng G, Salerno J, Cao Z, Pagano P, Lambeth J. Identification and characterization of VPO1, a new animal heme-containing peroxidase. Free Radic Biol Med. 2008;45:1682-94 pubmed publisher..5 mM. When co-expressed in cells, VPO1 can use H(2)O(2) produced by NADPH oxidase enzymes. VPO1 is likely to carry out peroxidative reactions previously attributed exclusively to myeloperoxidase in the vascular system. ..
- Waters S, Wilson C, Lewandoski M. Cloning and embryonic expression analysis of the mouse Gbx1 gene. Gene Expr Patterns. 2003;3:313-7 pubmed..of a cDNA encoding the complete mouse Gbx1 coding region as well as a comparative expression analysis of Gbx1 and Gbx2 during murine development...
- Koo S, Hill J, Hwang C, Lin Z, Millen K, Wu D. Lmx1a maintains proper neurogenic, sensory, and non-sensory domains in the mammalian inner ear. Dev Biol. 2009;333:14-25 pubmed publisher..Furthermore, aberrant and ectopic sensory organs are observed; most striking among these is vestibular-like hair cells located in the cochlear duct. ..
- Riccomagno M, Martinu L, Mulheisen M, Wu D, Epstein D. Specification of the mammalian cochlea is dependent on Sonic hedgehog. Genes Dev. 2002;16:2365-78 pubmed..Taken together, our data support a model whereby auditory cell fates in the otic vesicle are established by the direct action of Shh. ..
- Calmont A, Ivins S, van Bueren K, Papangeli I, Kyriakopoulou V, Andrews W, et al. Tbx1 controls cardiac neural crest cell migration during arch artery development by regulating Gbx2 expression in the pharyngeal ectoderm. Development. 2009;136:3173-83 pubmed publisher..We investigated the crucial role played by the homeobox-containing transcription factor Gbx2 downstream of Tbx1...
- Achim K, Peltopuro P, Lahti L, Li J, Salminen M, Partanen J. Distinct developmental origins and regulatory mechanisms for GABAergic neurons associated with dopaminergic nuclei in the ventral mesodiencephalic region. Development. 2012;139:2360-70 pubmed publisher..These results suggest unique migratory pathways for the precursors of important GABAergic neuron subpopulations, and provide the basis for understanding diversity within midbrain GABAergic neurons. ..
- Liu A, Losos K, Joyner A. FGF8 can activate Gbx2 and transform regions of the rostral mouse brain into a hindbrain fate. Development. 1999;126:4827-38 pubmed..5 (E9.5) caudal forebrain explants, but also can induce the hindbrain gene Gbx2 and alter the expression of Wnt1 in both midbrain and caudal forebrain explants...
- Szabó N, Zhao T, Cankaya M, Stoykova A, Zhou X, Alvarez Bolado G. Interaction between axons and specific populations of surrounding cells is indispensable for collateral formation in the mammillary system. PLoS ONE. 2011;6:e20315 pubmed publisher..mouse lines carrying mutant alleles of genes expressed in defined subpopulations (including Pax6, Foxb1, Lrp6 and Gbx2) together with the use of an unambiguous genetic marker of mammillary axons revealed: 1) a specific group of Pax6-..
- Caprio C, Baldini A. p53 Suppression partially rescues the mutant phenotype in mouse models of DiGeorge syndrome. Proc Natl Acad Sci U S A. 2014;111:13385-90 pubmed publisher..We found that the Tbx1 and p53 proteins do not interact directly but both occupy a genetic element of Gbx2, which is required for aortic arch and cardiac outflow tract development, and is a known genetic interactor of Tbx1...
- Iwafuchi Doi M, Matsuda K, Murakami K, Niwa H, Tesar P, Aruga J, et al. Transcriptional regulatory networks in epiblast cells and during anterior neural plate development as modeled in epiblast stem cells. Development. 2012;139:3926-37 pubmed publisher..The direct interaction of these factors with enhancers of Otx2, Hesx1 and Sox2 genes was demonstrated. Thus, a combination of regulatory processes that suppresses non-ANP lineages and promotes neural plate development determines the ANP...
- Yamaguchi T, Bradley A, McMahon A, Jones S. A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development. 1999;126:1211-23 pubmed..The reduced number of proliferating cells in both the progress zone and the primitive streak mesoderm suggests that one function of Wnt5a is to regulate the proliferation of progenitor cells. ..
- Raft S, Andrade L, Shao D, Akiyama H, Henkemeyer M, Wu D. Ephrin-B2 governs morphogenesis of endolymphatic sac and duct epithelia in the mouse inner ear. Dev Biol. 2014;390:51-67 pubmed publisher..We propose that developmental dysplasias described here are a gene dose-sensitive cause of the vestibular dysfunction observed in EphB-Efnb2 signaling-deficient mice. ..
- Chapman G, Rathjen P. Sequence and evolutionary conservation of the murine Gbx-2 homeobox gene. FEBS Lett. 1995;364:289-92 pubmed..The homeodomain differs at only three positions out of 60 and these can be used to subdivide the GBX class homeodomains into 2 sub-classes. ..
- Fossat N, Le Greneur C, Beby F, Vincent S, Godement P, Chatelain G, et al. A new GFP-tagged line reveals unexpected Otx2 protein localization in retinal photoreceptors. BMC Dev Biol. 2007;7:122 pubmed..This opens up the way to live imaging of a highly dynamic actor of brain development and can be adapted to any mutant background to probe for genetic interaction between Otx2 and the mutated gene. ..
- Kitajima S, Takagi A, Inoue T, Saga Y. MesP1 and MesP2 are essential for the development of cardiac mesoderm. Development. 2000;127:3215-26 pubmed..These results strongly indicate that the defect in the cranial-cardiac mesoderm is cell-autonomous, whereas the defect in the paraxial mesoderm is a non-cell-autonomous secondary consequence. ..
- Gottlieb S, Hanes S, Golden J, Oakey R, Budarf M. Goosecoid-like, a gene deleted in DiGeorge and velocardiofacial syndromes, recognizes DNA with a bicoid-like specificity and is expressed in the developing mouse brain. Hum Mol Genet. 1998;7:1497-505 pubmed
- Huffman K, Garel S, Rubenstein J. Fgf8 regulates the development of intra-neocortical projections. J Neurosci. 2004;24:8917-23 pubmed..we found that the neonatal intra-neocortical projection pattern was not perturbed when thalamic input was absent in Gbx2 mutants...
- Hirata H, Tomita K, Bessho Y, Kageyama R. Hes1 and Hes3 regulate maintenance of the isthmic organizer and development of the mid/hindbrain. EMBO J. 2001;20:4454-66 pubmed..These results indicate that Hes1 and Hes3 prevent premature differentiation and maintain the organizer activity of the isthmic cells, thereby regulating the development of the midbrain and anterior hindbrain. ..
- Schwarz M, Alvarez Bolado G, Dressler G, Urbanek P, Busslinger M, Gruss P. Pax2/5 and Pax6 subdivide the early neural tube into three domains. Mech Dev. 1999;82:29-39 pubmed..of Pax6, (the molecular determinant of posterior commissure), and a rostral shift of the territory of expression of Gbx2 and Otp (markers for the pons), towards the caudal diencephalon...
- Morello F, Prasad A, Rehberg K, Vieira de SÃ¡ R, AntÃ³n BolaÃ±os N, Leyva Díaz E, et al. Frizzled3 Controls Axonal Polarity and Intermediate Target Entry during Striatal Pathway Development. J Neurosci. 2015;35:14205-19 pubmed publisher..e., striatal and thalamocortical axons). ..
- Cunningham T, Colas A, Duester G. Early molecular events during retinoic acid induced differentiation of neuromesodermal progenitors. Biol Open. 2016;5:1821-1833 pubmed publisher..using RA-deficient Raldh2-/- embryos identified novel examples of RA activation (Nkx1-2, Zfp503, Zfp703, Gbx2, Fgf15, Nt5e) or RA repression (Id1) of genes expressed in the NMP niche or progeny...