Gene Symbol: Nkx6-2
Description: NK6 homeobox 2
Alias: Gtx, Nkx6.2, homeobox protein Nkx-6.2, Drosophila NK transcription factor related, gene family 6, locus 2, NK6 transcription factor related, locus 2, glial and testis specific homeobox
Species: mouse
Products:     Nkx6-2

Top Publications

  1. Flames N, Pla R, Gelman D, Rubenstein J, Puelles L, Marin O. Delineation of multiple subpallial progenitor domains by the combinatorial expression of transcriptional codes. J Neurosci. 2007;27:9682-95 pubmed
    ..Furthermore, the results of microtransplantation experiments in vivo corroborate that anatomically defined regions of the mouse subpallium, such as the medial ganglionic eminence, can be subdivided into functionally distinct domains. ..
  2. Cai J, Qi Y, Wu R, Modderman G, Fu H, Liu R, et al. Mice lacking the Nkx6.2 (Gtx) homeodomain transcription factor develop and reproduce normally. Mol Cell Biol. 2001;21:4399-403 pubmed
    ..Expression of Nkx6.2 (Gtx) was previously observed in the embryonic neural tube, testis, and differentiating oligodendrocytes...
  3. Vallstedt A, Muhr J, Pattyn A, Pierani A, Mendelsohn M, Sander M, et al. Different levels of repressor activity assign redundant and specific roles to Nkx6 genes in motor neuron and interneuron specification. Neuron. 2001;31:743-55 pubmed
  4. Fogarty M, Grist M, Gelman D, Marin O, Pachnis V, Kessaris N. Spatial genetic patterning of the embryonic neuroepithelium generates GABAergic interneuron diversity in the adult cortex. J Neurosci. 2007;27:10935-46 pubmed
  5. Southwood C, He C, Garbern J, Kamholz J, Arroyo E, Gow A. CNS myelin paranodes require Nkx6-2 homeoprotein transcriptional activity for normal structure. J Neurosci. 2004;24:11215-25 pubmed
  6. Stenman J, Wang B, Campbell K. Tlx controls proliferation and patterning of lateral telencephalic progenitor domains. J Neurosci. 2003;23:10568-76 pubmed
    ..Our results show that, although Gsh2 and Tlx have additive effects on striatal development, they differentially regulate the establishment of ventral pallial identity. ..
  7. Coppola E, Pattyn A, Guthrie S, Goridis C, Studer M. Reciprocal gene replacements reveal unique functions for Phox2 genes during neural differentiation. EMBO J. 2005;24:4392-403 pubmed
    ..Therefore, our analysis strongly indicates that biochemical differences between the proteins rather than temporal regulation of their expression account for the specific function of each paralogue. ..
  8. Alanentalo T, Chatonnet F, Karlen M, Sulniute R, Ericson J, Andersson E, et al. Cloning and analysis of Nkx6.3 during CNS and gastrointestinal development. Gene Expr Patterns. 2006;6:162-70 pubmed
    ..2 both in the CNS and in the gut. Transient Nkx6.2 expression was also detected in the developing pancreas. However, analysis of Nkx6.2(-/-) mice did not display any obvious aberrations of pancreatic or stomach development. ..
  9. Gelman D, Griveau A, Dehorter N, Teissier A, Varela C, Pla R, et al. A wide diversity of cortical GABAergic interneurons derives from the embryonic preoptic area. J Neurosci. 2011;31:16570-80 pubmed publisher
    ..Together with earlier findings, our results also suggest that the POA generates nearly 10% of the GABAergic interneurons in the cerebral cortex of the mouse. ..

More Information


  1. Cai J, Qi Y, Hu X, Tan M, Liu Z, Zhang J, et al. Generation of oligodendrocyte precursor cells from mouse dorsal spinal cord independent of Nkx6 regulation and Shh signaling. Neuron. 2005;45:41-53 pubmed
    ..In addition, we provide genetic evidence that oligodendrogenesis can occur in the absence of hedgehog receptor Smoothened, which is essential for all hedgehog signaling. ..
  2. Yu W, Wang Y, McDonnell K, Stephen D, Bai C. Patterning of ventral telencephalon requires positive function of Gli transcription factors. Dev Biol. 2009;334:264-75 pubmed publisher
    ..Together, these studies unravel a role for Gli transcription factors in mediating Shh signaling to control specification, differentiation and positioning of ventral telencephalic neurons. ..
  3. Lieberam I, Agalliu D, Nagasawa T, Ericson J, Jessell T. A Cxcl12-CXCR4 chemokine signaling pathway defines the initial trajectory of mammalian motor axons. Neuron. 2005;47:667-79 pubmed
    ..In its absence, these neurons adopt a dMN-like trajectory, despite preservation of their vMN transcriptional identity. Thus, the status of Cxcr4 signaling helps to determine the initial axonal trajectory of mammalian motor neurons. ..
  4. De Marco Garcia N, Jessell T. Early motor neuron pool identity and muscle nerve trajectory defined by postmitotic restrictions in Nkx6.1 activity. Neuron. 2008;57:217-31 pubmed publisher
    ..Our findings provide genetic evidence that neurons within motor pools possess an early transcriptional identity that controls target muscle specificity. ..
  5. Stuebner S, Faus Kessler T, Fischer T, Wurst W, Prakash N. Fzd3 and Fzd6 deficiency results in a severe midbrain morphogenesis defect. Dev Dyn. 2010;239:246-60 pubmed publisher
    ..Fzd3 and Fzd6 thus control proper midbrain morphogenesis by a yet unknown mechanism in the mouse. ..
  6. Waite M, Skidmore J, Billi A, Martin J, Martin D. GABAergic and glutamatergic identities of developing midbrain Pitx2 neurons. Dev Dyn. 2011;240:333-46 pubmed publisher
    ..Our data suggest that PITX2 is present in regionally restricted subpopulations of midbrain neurons and may have unique functions that promote GABAergic and glutamatergic differentiation. ..
  7. Awatramani R, Beesley J, Yang H, Jiang H, Cambi F, Grinspan J, et al. Gtx, an oligodendrocyte-specific homeodomain protein, has repressor activity. J Neurosci Res. 2000;61:376-87 pubmed
    ..b>Gtx, a member of the homeodomain family of transcriptional factors, is a candidate regulator of myelin gene expression, ..
  8. Madrigal M, Moreno Bravo J, Martínez López J, Martínez S, Puelles E. Mesencephalic origin of the rostral Substantia nigra pars reticulata. Brain Struct Funct. 2016;221:1403-12 pubmed publisher
    ..Understanding the development, molecular identity and functional characteristics of these diverse neuronal populations might lead to better diagnosis and treatment of several forms of neurological and psychiatric disease. ..
  9. Lei Q, Zelman A, Kuang E, Li S, Matise M. Transduction of graded Hedgehog signaling by a combination of Gli2 and Gli3 activator functions in the developing spinal cord. Development. 2004;131:3593-604 pubmed
    ..Thus, multiple ventral neuronal types can develop in the absence of Gli function, but require balanced Gli protein activities for their correct patterning and differentiation. ..
  10. Vernersson E, Khoo N, Henriksson M, Roos G, Palmer R, Hallberg B. Characterization of the expression of the ALK receptor tyrosine kinase in mice. Gene Expr Patterns. 2006;6:448-61 pubmed
    ..Furthermore, ALK is also expressed in the eye, nasal epithelium, olfactory nerve, tongue, skin, tissue surrounding the esophagus, stomach and midgut but not the hindgut. Expression of ALK is also found in testis and ovary. ..
  11. Thélie A, Desiderio S, Hanotel J, Quigley I, Van Driessche B, Rodari A, et al. Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus. Development. 2015;142:3416-28 pubmed publisher
  12. Lih C, Cohen S, Wang C, Lin Chao S. The platelet-derived growth factor alpha-receptor is encoded by a growth-arrest-specific (gas) gene. Proc Natl Acad Sci U S A. 1996;93:4617-22 pubmed
    ..We suggest that accumulation of the PDGFalphaR gene product may facilitate the exiting of cells from growth arrest upon mitogenic stimulation by PDGF, leading to the state of "competence" required for cell cycling. ..
  13. Dias J, Alekseenko Z, Applequist J, Ericson J. Tgfβ signaling regulates temporal neurogenesis and potency of neural stem cells in the CNS. Neuron. 2014;84:927-39 pubmed publisher
    ..Our study establishes Tgfβ as a regulator of temporal identity and potency of neural stem cells, and provides proof of concept that Tgfβ can be applied to modulate temporal specification of neurons in stem cell engineering. ..
  14. Snouffer A, Brown D, Lee H, Walsh J, Lupu F, Norman R, et al. Cell Cycle-Related Kinase (CCRK) regulates ciliogenesis and Hedgehog signaling in mice. PLoS Genet. 2017;13:e1006912 pubmed publisher
  15. Pedersen J, Nelson S, Jorgensen M, Henseleit K, Fujitani Y, Wright C, et al. Endodermal expression of Nkx6 genes depends differentially on Pdx1. Dev Biol. 2005;288:487-501 pubmed
    ..2 or Nkx6.3 expression in anterior chicken endoderm. These results demonstrate that Nkx6.1 lies downstream of Pdx1 in a genetic pathway and that Pdx1 is required and sufficient for Nkx6.1 expression in the early foregut endoderm. ..
  16. Uhler J, Garbern J, Yang L, Kamholz J, Mellerick D. Nk6, a novel Drosophila homeobox gene regulated by vnd. Mech Dev. 2002;116:105-16 pubmed
    ..Conversely, vnd-overexpression leads to ectopic Nk6 expression in the brain. These findings further highlight the importance of interactions between Nk(x)-type genes in regulating their expression. ..
  17. Vallstedt A, Klos J, Ericson J. Multiple dorsoventral origins of oligodendrocyte generation in the spinal cord and hindbrain. Neuron. 2005;45:55-67 pubmed
    ..Based on these findings, we propose that oligodendrocytes derive from several distinct positional origins and that the activation of Olig1/2 at different positions is controlled by distinct genetic programs. ..
  18. Sousa V, Miyoshi G, Hjerling Leffler J, Karayannis T, Fishell G. Characterization of Nkx6-2-derived neocortical interneuron lineages. Cereb Cortex. 2009;19 Suppl 1:i1-10 pubmed publisher
  19. Pattyn A, Vallstedt A, Dias J, Sander M, Ericson J. Complementary roles for Nkx6 and Nkx2 class proteins in the establishment of motoneuron identity in the hindbrain. Development. 2003;130:4149-59 pubmed
    ..Thus, both visceral and somatic motoneuron differentiation appear to rely on the combined activity of cell intrinsic determinants, rather than on a single key determinant of neuronal cell fate. ..
  20. Awatramani R, Scherer S, Grinspan J, Collarini E, Skoff R, O HAGAN D, et al. Evidence that the homeodomain protein Gtx is involved in the regulation of oligodendrocyte myelination. J Neurosci. 1997;17:6657-68 pubmed
    We have investigated the patterns of postnatal brain expression and DNA binding of Gtx, a homeodomain transcription factor...
  21. Baudet C, Pozas E, Adameyko I, Andersson E, Ericson J, Ernfors P. Retrograde signaling onto Ret during motor nerve terminal maturation. J Neurosci. 2008;28:963-75 pubmed publisher
    ..Thus, Ret transmits a signal in motor nerve terminals that participate in the organization and maturation of presynaptic specializations during development and during regeneration in the adult. ..
  22. Xu Q, Guo L, Moore H, Waclaw R, Campbell K, Anderson S. Sonic hedgehog signaling confers ventral telencephalic progenitors with distinct cortical interneuron fates. Neuron. 2010;65:328-40 pubmed publisher
    ..These results indicate that cortical interneuron diversity, a major determinant of cortical function, is critically influenced by differential levels of SHH signaling within the ventral telencephalon. ..
  23. Novitch B, Chen A, Jessell T. Coordinate regulation of motor neuron subtype identity and pan-neuronal properties by the bHLH repressor Olig2. Neuron. 2001;31:773-89 pubmed
    ..Together, these studies show that Olig2 has a critical role in integrating diverse features of motor neuron differentiation in the developing spinal cord. ..
  24. Müller M, Jabs N, Lorke D, Fritzsch B, Sander M. Nkx6.1 controls migration and axon pathfinding of cranial branchio-motoneurons. Development. 2003;130:5815-26 pubmed
    ..Taken together, our findings demonstrate a requirement for Nkx6.1 in the development of postmitotic motoneurons, and suggest a cell-autonomous function in the control of branchio-motoneuron migration. ..
  25. 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...
  26. Pachikara A, Dolson D, Martinu L, Riccomagno M, Jeong Y, Epstein D. Activation of Class I transcription factors by low level Sonic hedgehog signaling is mediated by Gli2-dependent and independent mechanisms. Dev Biol. 2007;305:52-62 pubmed
  27. Perez Balaguer A, Puelles E, Wurst W, Martinez S. Shh dependent and independent maintenance of basal midbrain. Mech Dev. 2009;126:301-13 pubmed publisher
    ..Based on our results and recently published data, we suggest the existence of a specific genetic pathway for the specification of the mesencephalic red nucleus. Foxa2 could be the candidate gene that might control this genetic pathway. ..
  28. Nelson S, Schaffer A, Sander M. The transcription factors Nkx6.1 and Nkx6.2 possess equivalent activities in promoting beta-cell fate specification in Pdx1+ pancreatic progenitor cells. Development. 2007;134:2491-500 pubmed
    ..2 in endocrine differentiation are a consequence of their divergent spatiotemporal expression domains rather than their biochemical activities and implies that both Nkx6.1 and Nkx6.2 possess alpha- and beta-cell-specifying activities. ..
  29. Cai J, Zhu Q, Zheng K, Li H, Qi Y, Cao Q, et al. Co-localization of Nkx6.2 and Nkx2.2 homeodomain proteins in differentiated myelinating oligodendrocytes. Glia. 2010;58:458-68 pubmed publisher
    Recent studies have suggested that Nkx6.2/Gtx and Nkx2.2 homeodomain transcription factors are involved in the regulation of oligodendrocyte maturation and/or myelination which occur predominantly in postnatal stages...
  30. Gelman D, Martini F, Nóbrega Pereira S, Pierani A, Kessaris N, Marin O. The embryonic preoptic area is a novel source of cortical GABAergic interneurons. J Neurosci. 2009;29:9380-9 pubmed publisher
  31. Moreno Bravo J, Perez Balaguer A, Martinez S, Puelles E. Dynamic expression patterns of Nkx6.1 and Nkx6.2 in the developing mes-diencephalic basal plate. Dev Dyn. 2010;239:2094-101 pubmed publisher
    ..The nuclei integrated in this domain would be the rostral interstitial nucleus, the interstitial nucleus of Cajal, and a mesencephalic equivalent to these nuclei. ..
  32. Hochstim C, Deneen B, Lukaszewicz A, Zhou Q, Anderson D. Identification of positionally distinct astrocyte subtypes whose identities are specified by a homeodomain code. Cell. 2008;133:510-22 pubmed publisher
  33. Hwang D, Hong S, Jeong J, Choi S, Kim H, Kim J, et al. Vesicular monoamine transporter 2 and dopamine transporter are molecular targets of Pitx3 in the ventral midbrain dopamine neurons. J Neurochem. 2009;111:1202-12 pubmed publisher
  34. Persson M, Stamataki D, te Welscher P, Andersson E, Böse J, Ruther U, et al. Dorsal-ventral patterning of the spinal cord requires Gli3 transcriptional repressor activity. Genes Dev. 2002;16:2865-78 pubmed
    ..Together these data raise the possibility that Gli proteins act as common mediators integrating Shh signals, and other sources of positional information, to control patterning throughout the ventral neural tube. ..
  35. Qiu M, Shimamura K, Sussel L, Chen S, Rubenstein J. Control of anteroposterior and dorsoventral domains of Nkx-6.1 gene expression relative to other Nkx genes during vertebrate CNS development. Mech Dev. 1998;72:77-88 pubmed
    ..1 expression. While the notochord can induce Nkx-6.1 expression in the anterior neural plate, sonic hedgehog protein does not, suggesting that the notochord produces additional molecules that can regulate ventral patterning. ..
  36. Komuro I, Schalling M, Jahn L, Bodmer R, Jenkins N, Copeland N, et al. Gtx: a novel murine homeobox-containing gene, expressed specifically in glial cells of the brain and germ cells of testis, has a transcriptional repressor activity in vitro for a serum-inducible promoter. EMBO J. 1993;12:1387-401 pubmed
    ..We describe here a novel murine homeobox gene, denoted Gtx, which in adult animals is specifically expressed within glial cells of the central nervous system, including the ..
  37. Schaffer A, Freude K, Nelson S, Sander M. Nkx6 transcription factors and Ptf1a function as antagonistic lineage determinants in multipotent pancreatic progenitors. Dev Cell. 2010;18:1022-9 pubmed publisher
    ..Thus, cross-antagonism between Nkx6 and Ptf1a in multipotent progenitors governs the equilibrium between endocrine and acinar cell neogenesis required for normal pancreas development. ..
  38. Pattyn A, Vallstedt A, Dias J, Samad O, Krumlauf R, Rijli F, et al. Coordinated temporal and spatial control of motor neuron and serotonergic neuron generation from a common pool of CNS progenitors. Genes Dev. 2003;17:729-37 pubmed
    ..These findings assign new roles for Nkx, Hox, and Phox2 proteins in the control of temporal neuronal fate determination, and link spatial and temporal patterning of CNS neuronal fates. ..
  39. Jacob J, Ferri A, Milton C, Prin F, Pla P, Lin W, et al. Transcriptional repression coordinates the temporal switch from motor to serotonergic neurogenesis. Nat Neurosci. 2007;10:1433-9 pubmed
    ..Moreover, the subsequent differentiation of central serotonergic neurons required both the suppression of VMN neurogenesis and the induction of downstream intrinsic determinants of serotonergic identity by Foxa2. ..
  40. Henseleit K, Nelson S, Kuhlbrodt K, Hennings J, Ericson J, Sander M. NKX6 transcription factor activity is required for alpha- and beta-cell development in the pancreas. Development. 2005;132:3139-49 pubmed
    ..We demonstrate that expression of Myt1 depends on overall Nkx6 gene dose, and therefore identify Myt1 as a possible downstream target of Nkx6 genes in the endocrine differentiation pathway. ..
  41. 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. ..
  42. Kaltezioti V, Antoniou D, Stergiopoulos A, Rozani I, Rohrer H, Politis P. Prox1 regulates Olig2 expression to modulate binary fate decisions in spinal cord neurons. J Neurosci. 2014;34:15816-31 pubmed publisher
    ..These observations indicate that Prox1 controls binary fate decisions between MNs and V2 interneurons in NPCs via direct repression of Olig2 gene regulatory elements. ..
  43. Hu J, Vogt D, Lindtner S, Sandberg M, Silberberg S, Rubenstein J. Coup-TF1 and Coup-TF2 control subtype and laminar identity of MGE-derived neocortical interneurons. Development. 2017;144:2837-2851 pubmed publisher
    ..These results have identified, in mouse, a transcriptional pathway that controls SST-PV fate. ..