Genomes and Genes
Gene Symbol: Tlx3
Description: T cell leukemia, homeobox 3
Alias: Hox11l2, Rnx, Tlx1l2, T-cell leukemia homeobox protein 3, homeo box 11-like 2, homeobox TLX-3, homeobox protein Hox-11L2, respiratory neuron homeobox protein
- Lopes C, Liu Z, Xu Y, Ma Q. Tlx3 and Runx1 act in combination to coordinate the development of a cohort of nociceptors, thermoceptors, and pruriceptors. J Neurosci. 2012;32:9706-15 pubmed publisher..Here we showed that the homeodomain transcription factor Tlx3, expressed broadly in DRG neurons, is required to establish most Runx1-dependent phenotypes, including the ..
- Hori K, Cholewa Waclaw J, Nakada Y, Glasgow S, Masui T, Henke R, et al. A nonclassical bHLH Rbpj transcription factor complex is required for specification of GABAergic neurons independent of Notch signaling. Genes Dev. 2008;22:166-78 pubmed publisher..its ability to interact with E-protein, is incapable of inducing GABAergic (Pax2)- and suppressing glutamatergic (Tlx3)-expressing cells in the chick and mouse neural tube...
- Divya T, Lalitha S, Parvathy S, Subashini C, Sanalkumar R, Dhanesh S, et al. Regulation of Tlx3 by Pax6 is required for the restricted expression of ChrnÎ±3 in Cerebellar Granule Neuron progenitors during development. Sci Rep. 2016;6:30337 pubmed publisherHomeobox gene Tlx3 is known to promote glutamatergic differentiation and is expressed in post-mitotic neurons of CNS...
- Zou M, Li S, Klein W, Xiang M. Brn3a/Pou4f1 regulates dorsal root ganglion sensory neuron specification and axonal projection into the spinal cord. Dev Biol. 2012;364:114-27 pubmed publisher..Our results together demonstrate a critical role for Brn3a in generating DRG sensory neuron diversity and regulating sensory afferent projections to the central targets. ..
- D Autréaux F, Coppola E, Hirsch M, Birchmeier C, Brunet J. Homeoprotein Phox2b commands a somatic-to-visceral switch in cranial sensory pathways. Proc Natl Acad Sci U S A. 2011;108:20018-23 pubmed publisher..Thus, the cranial sensory pathways, somatic and visceral, are related, and Phox2b serves as a developmental switch from the former to the latter...
- Wildner H, Muller T, Cho S, Bröhl D, Cepko C, Guillemot F, et al. dILA neurons in the dorsal spinal cord are the product of terminal and non-terminal asymmetric progenitor cell divisions, and require Mash1 for their development. Development. 2006;133:2105-13 pubmed..Our data allow us to assign to Mash1 a function in asymmetric cell divisions, and indicate that the factor coordinates cell cycle exit and specification in the one daughter that gives rise to a dILA neuron. ..
- Ravindran E, Hu H, Yuzwa S, Hernández Miranda L, Kraemer N, Ninnemann O, et al. Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-hindbrain malformation. PLoS Genet. 2017;13:e1006746 pubmed publisher..Our results highlight the crucial function of ARHGEF2 in human brain development and identify a mutation in ARHGEF2 as novel cause of a neurodevelopmental disorder. ..
- Liu Z, Li H, Hu X, Yu L, Liu H, Han R, et al. Control of precerebellar neuron development by Olig3 bHLH transcription factor. J Neurosci. 2008;28:10124-33 pubmed publisher..Therefore, Olig3 plays an important role in the fate specification and differentiation of caudal RL-derived neurons. ..
- Stubbusch J, Narasimhan P, Hennchen M, Huber K, Unsicker K, Ernsberger U, et al. Lineage and stage specific requirement for Dicer1 in sympathetic ganglia and adrenal medulla formation and maintenance. Dev Biol. 2015;400:210-23 pubmed publisher..noradrenergic and cholinergic sympathetic neurons is demonstrated by the selective increase in the expression of Tlx3 and the cholinergic marker genes VAChT and ChAT at E16.5...
- Stolt C, Schlierf A, Lommes P, Hillgärtner S, Werner T, Kosian T, et al. SoxD proteins influence multiple stages of oligodendrocyte development and modulate SoxE protein function. Dev Cell. 2006;11:697-709 pubmed..Our studies reveal a complex regulatory network between different groups of Sox proteins that is essential for proper progression of oligodendrocyte development. ..
- Onimaru H, Arata A, Arata S, Shirasawa S, Cleary M. In vitro visualization of respiratory neuron activity in the newborn mouse ventral medulla. Brain Res Dev Brain Res. 2004;153:275-9 pubmed..We also demonstrated optical images of the respiratory activity of two different lines of knock-out mice (Tlx3-/-, Pbx3-/-) that exhibit respiratory failure leading to neonatal death from dysfunction of central respiratory ..
- Pattyn A, Guillemot F, Brunet J. Delays in neuronal differentiation in Mash1/Ascl1 mutants. Dev Biol. 2006;295:67-75 pubmed..Finally, we provide evidence that the acceleration imposed by Mash1, regardless of the production of post-mitotic cells, affects differentiation itself, both generic and type-specific. ..
- Dauger S, Pattyn A, Lofaso F, Gaultier C, Goridis C, Gallego J, et al. Phox2b controls the development of peripheral chemoreceptors and afferent visceral pathways. Development. 2003;130:6635-42 pubmed
- 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. ..
- Wildner H, Gierl M, Strehle M, Pla P, Birchmeier C. Insm1 (IA-1) is a crucial component of the transcriptional network that controls differentiation of the sympatho-adrenal lineage. Development. 2008;135:473-81 pubmed..We demonstrate that the fetal lethality of Insm1 mutant mice is caused by catecholamine deficiency, which highlights the importance of Insm1 in the development of the sympatho-adrenal lineage. ..
- Espana A, Clotman F. Onecut factors control development of the Locus Coeruleus and of the mesencephalic trigeminal nucleus. Mol Cell Neurosci. 2012;50:93-102 pubmed publisher..Hence, we propose that OC factors are required at early developmental stages for differentiation of the MTN neurons that are in turn necessary for maintenance of the LC. ..
- Ding Y, Yin J, Xu H, Jacquin M, Chen Z. Formation of whisker-related principal sensory nucleus-based lemniscal pathway requires a paired homeodomain transcription factor, Drg11. J Neurosci. 2003;23:7246-54 pubmed..Our results demonstrate that Drg11 is essential for proper cellular differentiation and, subsequently, for the formation of the whisker-related lemniscal and cortical structures. ..
- Millen K, Steshina E, Iskusnykh I, Chizhikov V. Transformation of the cerebellum into more ventral brainstem fates causes cerebellar agenesis in the absence of Ptf1a function. Proc Natl Acad Sci U S A. 2014;111:E1777-86 pubmed publisher..Further, we propose that cerebellar agenesis represents a new, dorsal-to-ventral, cell fate misspecification phenotype in humans. ..
- Shirasawa S, Arata A, Onimaru H, Roth K, Brown G, Horning S, et al. Rnx deficiency results in congenital central hypoventilation. Nat Genet. 2000;24:287-90 pubmedThe genes Tlx1 (Hox11), Enx (Hox11L2, Tlx-2) and Rnx (Hox11L2, Tlx-3) constitute a family of orphan homeobox genes...
- Schüller U, Heine V, Mao J, Kho A, Dillon A, Han Y, et al. Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell. 2008;14:123-34 pubmed publisher..Thus, oncogenic Hh signaling promotes medulloblastoma from lineage-restricted granule cell progenitors. ..
- Bröhl D, Strehle M, Wende H, Hori K, Bormuth I, Nave K, et al. A transcriptional network coordinately determines transmitter and peptidergic fate in the dorsal spinal cord. Dev Biol. 2008;322:381-93 pubmed publisher..We conclude that a transcriptional network operates in maturing dorsal horn neurons that coordinately determines transmitter and peptidergic fate. ..
- Roberts C, Sonder A, Lumsden A, Korsmeyer S. Development expression of Hox11 and specification of splenic cell fate. Am J Pathol. 1995;146:1089-101 pubmed..1 and Hox1L1.2, were not expressed in a redundant pattern. Neither Hox11L1 nor Hox11L2 was expressed in the branchial arches or their motor nuclei within wild-type or Hox11-/- mice. Beginning at E11...
- Iskusnykh I, Steshina E, Chizhikov V. Loss of Ptf1a Leads to a Widespread Cell-Fate Misspecification in the Brainstem, Affecting the Development of Somatosensory and Viscerosensory Nuclei. J Neurosci. 2016;36:2691-710 pubmed publisher..Since loss-of-function PTF1A mutations were described in human patients, we suggest Ptf1a-dependent cell-fate misspecification as a novel mechanism of human brainstem pathology. ..
- Xu Y, Lopes C, Wende H, Guo Z, Cheng L, Birchmeier C, et al. Ontogeny of excitatory spinal neurons processing distinct somatic sensory modalities. J Neurosci. 2013;33:14738-48 pubmed publisher..Here we generated a new line of conditional knock-out (CKO) mice, in which the homeobox gene Tlx3 was removed in dI5 and dIL(B) cells...
- Iulianella A, Sharma M, Vanden Heuvel G, Trainor P. Cux2 functions downstream of Notch signaling to regulate dorsal interneuron formation in the spinal cord. Development. 2009;136:2329-34 pubmed publisher..Together with the requirement for Cux2 in cell cycle progression, our work highlights the mechanistic complexity in balancing neural progenitor maintenance and differentiation during spinal cord neurogenesis...
- Regadas I, Soares Dos Reis R, Falcão M, Matos M, Monteiro F, Lima D, et al. Dual role of Tlx3 as modulator of Prrxl1 transcription and phosphorylation. Biochim Biophys Acta. 2014;1839:1121-31 pubmed publisher..cord nociceptive circuitry depends on a group of homeodomain transcription factors that includes Prrxl1, Brn3a and Tlx3. By the use of epistatic analysis, it was suggested that Tlx3 and Brn3a, which highly co-localize with Prrxl1 in ..
- Rebelo S, Reguenga C, Osório L, Pereira C, Lopes C, Lima D. DRG11 immunohistochemical expression during embryonic development in the mouse. Dev Dyn. 2007;236:2653-60 pubmed..5 up to the same early post-natal ages in several cranial sensory ganglia and brain nuclei. These results suggest that DRG11 is required for the establishment of the first neuronal sensory relay along development. ..
- Kondo T, Sheets P, Zopf D, Aloor H, Cummins T, Chan R, et al. Tlx3 exerts context-dependent transcriptional regulation and promotes neuronal differentiation from embryonic stem cells. Proc Natl Acad Sci U S A. 2008;105:5780-5 pubmed publisherThe T cell leukemia 3 (Tlx3) gene has been implicated in specification of glutamatergic sensory neurons in the spinal cord. In cranial sensory ganglia, Tlx3 is highly expressed in differentiating neurons during early embryogenesis...
- Rojas A, Schachterle W, Xu S, Martin F, Black B. Direct transcriptional regulation of Gata4 during early endoderm specification is controlled by FoxA2 binding to an intronic enhancer. Dev Biol. 2010;346:346-55 pubmed publisher..These studies identify Gata4 as a direct transcriptional target of FoxA2 in the hierarchy of the transcriptional regulatory network that controls the development of the definitive endoderm. ..
- Xiang C, Zhang K, Yin J, Arends J, Erzurumlu R, Jacquin M, et al. The transcription factor, Lmx1b, is necessary for the development of the principal trigeminal nucleus-based lemniscal pathway. Mol Cell Neurosci. 2010;44:394-403 pubmed publisher..Rescued PrV cells in Lmx1b/Bax double (-)(/)(-)s failed to rescue whisker-related PrV pattern formation. Thus, Lmx1b and Drg11 may act in the same genetic signaling pathway that is essential for PrV pattern formation. ..
- Shimomura A, Patel D, Wilson S, Koehler K, Khanna R, Hashino E. Tlx3 promotes glutamatergic neuronal subtype specification through direct interactions with the chromatin modifier CBP. PLoS ONE. 2015;10:e0135060 pubmed publisher..The homeodomain transcription factor, T-cell leukemia 3 (Tlx3), functions as the master neuronal fate regulator by instructively promoting the specification of glutamatergic ..
- Avraham O, Hadas Y, Vald L, Hong S, Song M, Klar A. Motor and dorsal root ganglion axons serve as choice points for the ipsilateral turning of dI3 axons. J Neurosci. 2010;30:15546-57 pubmed publisher..The axonal patterning of dI3 neurons, revealed in this study, highlights the role of established axonal cues-the DRG and motor axons-as intermediate guidepost cues for dI3 axons. ..
- Rebelo S, Reguenga C, Lopes C, Lima D. Prrxl1 is required for the generation of a subset of nociceptive glutamatergic superficial spinal dorsal horn neurons. Dev Dyn. 2010;239:1684-94 pubmed publisher..Here we demonstrate that the differential expression of the homeodomain transcription factors Prrxl1 (DRG11), Tlx3, and Lmx1b defines various subpopulations of spinal cord dorsal horn glutamatergic early born and late born neurons...
- Xu Y, Lopes C, Qian Y, Liu Y, Cheng L, Goulding M, et al. Tlx1 and Tlx3 coordinate specification of dorsal horn pain-modulatory peptidergic neurons. J Neurosci. 2008;28:4037-46 pubmed publisher..Here, we used genetic fate mapping to show that Tlx3(+) spinal cord neurons and their derivatives represent a heterogeneous population of neurons, marked by partially ..
- Kriks S, Lanuza G, Mizuguchi R, Nakafuku M, Goulding M. Gsh2 is required for the repression of Ngn1 and specification of dorsal interneuron fate in the spinal cord. Development. 2005;132:2991-3002 pubmed..Our results provide evidence that genetic interactions involving repression of Ngn1 by Gsh2 promote the differentiation of dI3 neurons from class A progenitors. ..
- Peirs C, Williams S, Zhao X, Walsh C, Gedeon J, Cagle N, et al. Dorsal Horn Circuits for Persistent Mechanical Pain. Neuron. 2015;87:797-812 pubmed publisher..Lastly, using inflammatory and neuropathic pain models, we show that multiple microcircuits in the dorsal horn encode this form of pain. ..
- Dear T, Sanchez Garcia I, Rabbitts T. The HOX11 gene encodes a DNA-binding nuclear transcription factor belonging to a distinct family of homeobox genes. Proc Natl Acad Sci U S A. 1993;90:4431-5 pubmed..These all contain a threonine residue in place of the more common isoleucine or valine in helix 3 of the homeodomain. HOX11 therefore appears to belong to a family of DNA-binding transactivators of transcription. ..
- Le Dreau G, Garcia Campmany L, Rabadán M, Ferronha T, Tozer S, Briscoe J, et al. Canonical BMP7 activity is required for the generation of discrete neuronal populations in the dorsal spinal cord. Development. 2012;139:259-68 pubmed publisher..Together, these data establish a novel role for BMP7 in primary neurogenesis, the process by which a neural progenitor exits the cell cycle and enters the terminal differentiation pathway. ..
- Rhee J, Arata A, Selleri L, Jacobs Y, Arata S, Onimaru H, et al. Pbx3 deficiency results in central hypoventilation. Am J Pathol. 2004;165:1343-50 pubmed..This partially phenocopies the defect in mice deficient for Rnx, a metaHox homeodomain transcription factor, that we demonstrate here is capable of forming a DNA-binding complex ..
- Jacob J, Storm R, Castro D, Milton C, Pla P, Guillemot F, et al. Insm1 (IA-1) is an essential component of the regulatory network that specifies monoaminergic neuronal phenotypes in the vertebrate hindbrain. Development. 2009;136:2477-85 pubmed publisher..Thus, Insm1 regulates the synthesis of distinct monoaminergic neurotransmitters by acting combinatorially with, or independently of, Ascl1 in specific monoaminergic populations. ..
- Liu B, Liu Z, Chen T, Li H, Qiang B, Yuan J, et al. Selective expression of Bhlhb5 in subsets of early-born interneurons and late-born association neurons in the spinal cord. Dev Dyn. 2007;236:829-35 pubmed..At late stages of development, Bhlhb5 expression is detected in a subset of late-born dorsal association interneurons that migrate into the uppermost layer of the dorsal horn. ..
- Zechner D, Muller T, Wende H, Walther I, Taketo M, Crenshaw E, et al. Bmp and Wnt/beta-catenin signals control expression of the transcription factor Olig3 and the specification of spinal cord neurons. Dev Biol. 2007;303:181-90 pubmed..We conclude that Wnt/beta-catenin and BMP signals coordinately control the specification of dorsal neurons in the spinal cord. ..
- Furlan A, Lübke M, Adameyko I, Lallemend F, Ernfors P. The transcription factor Hmx1 and growth factor receptor activities control sympathetic neurons diversification. EMBO J. 2013;32:1613-25 pubmed publisher..The homeobox transcription factor HMX1 represses Tlx3 and Ret, induces TrkA and maintains tyrosine hydroxylase (Th) expression in precursors, thus driving segregation of ..
- Horner V, Caspary T. Disrupted dorsal neural tube BMP signaling in the cilia mutant Arl13b hnn stems from abnormal Shh signaling. Dev Biol. 2011;355:43-54 pubmed publisher..We demonstrate that Arl13b is required non-autonomously for BMP signaling and Wnt ligand expression, indicating that the abnormal Shh signaling environment in Arl13b(hnn) embryos indirectly causes dorsal defects. ..
- Ross S, Mardinly A, McCord A, Zurawski J, Cohen S, Jung C, et al. Loss of inhibitory interneurons in the dorsal spinal cord and elevated itch in Bhlhb5 mutant mice. Neuron. 2010;65:886-98 pubmed publisher..Our findings suggest that Bhlhb5 is required for the survival of a specific population of inhibitory interneurons that regulate pruritus, and provide evidence that the loss of inhibitory synaptic input results in abnormal itch. ..
- Chen Y, Takano Maruyama M, Fritzsch B, Gaufo G. Hoxb1 controls anteroposterior identity of vestibular projection neurons. PLoS ONE. 2012;7:e34762 pubmed publisher..Moreover, at the expense of Phox2a, the glutamatergic determinants Lmx1b and Tlx3 were ectopically expressed by dB2 neurons...
- Bernard O, Busson LeConiat M, Ballerini P, Mauchauffe M, Della Valle V, Monni R, et al. A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia. Leukemia. 2001;15:1495-504 pubmed..The Hox11L2 gene was found to be transcriptionally activated as a result of the translocation, probably under the influence ..
- Qian Y, Fritzsch B, Shirasawa S, Chen C, Choi Y, Ma Q. Formation of brainstem (nor)adrenergic centers and first-order relay visceral sensory neurons is dependent on homeodomain protein Rnx/Tlx3. Genes Dev. 2001;15:2533-45 pubmed..precursor cells, and can be prospectively identified by combinatorial expression of two homeobox genes, Rnx and Phox2 (Phox2a or Phox2b). It was previously shown that Rnx-deficient mice die from respiratory failure...
- Huang M, Huang T, Xiang Y, Xie Z, Chen Y, Yan R, et al. Ptf1a, Lbx1 and Pax2 coordinate glycinergic and peptidergic transmitter phenotypes in dorsal spinal inhibitory neurons. Dev Biol. 2008;322:394-405 pubmed publisher..Our studies therefore suggest a coordinated and hierarchical specification of a variety of neurotransmitters in dorsal spinal inhibitory neurons. ..
- Wildner H, Das Gupta R, Bröhl D, Heppenstall P, Zeilhofer H, Birchmeier C. Genome-wide expression analysis of Ptf1a- and Ascl1-deficient mice reveals new markers for distinct dorsal horn interneuron populations contributing to nociceptive reflex plasticity. J Neurosci. 2013;33:7299-307 pubmed publisher..Functional experiments in isolated spinal cords showed that the Ascl1-dependent inhibitory interneurons are key players of nociceptive reflex plasticity. ..
- Huang T, Hu J, Wang B, Nie Y, Geng J, Cheng L. Tlx3 controls cholinergic transmitter and Peptide phenotypes in a subset of prenatal sympathetic neurons. J Neurosci. 2013;33:10667-75 pubmed publisher..In this study, we found that the expression of transcription factor Tlx3 was progressively restricted to a small population of embryonic sympathetic neurons in mice...