Gene Symbol: Irx3
Description: Iroquois related homeobox 3
Alias: AI894186, iroquois-class homeodomain protein IRX-3, homeodomain protein IRXB1, iroquois homeobox protein 3
Species: mouse
Products:     Irx3

Top Publications

  1. Bosse A, Zülch A, Becker M, Torres M, Gomez Skarmeta J, Modolell J, et al. Identification of the vertebrate Iroquois homeobox gene family with overlapping expression during early development of the nervous system. Mech Dev. 1997;69:169-81 pubmed
    ..These patterns implicate them in a number of embryonic developmental processes: the A/P and D/V patterning of specific regions of the central nervous system (CNS), and regionalization of the otic vesicle, branchial epithelium and limbs. ..
  2. Mukouyama Y, Deneen B, Lukaszewicz A, Novitch B, Wichterle H, Jessell T, et al. Olig2+ neuroepithelial motoneuron progenitors are not multipotent stem cells in vivo. Proc Natl Acad Sci U S A. 2006;103:1551-6 pubmed
    ..These results do not support the commonly held view that most neuroepithelial cells in the embryonic CNS VZ are stem cells in vivo. ..
  3. Niederreither K, Vermot J, Messaddeq N, Schuhbaur B, Chambon P, Dolle P. Embryonic retinoic acid synthesis is essential for heart morphogenesis in the mouse. Development. 2001;128:1019-31 pubmed
    ..However, cardiac neural crest cells cannot be properly rescued in Raldh2(-/- )embryos, leading to outflow tract septation defects. ..
  4. Stratigopoulos G, Padilla S, LeDuc C, Watson E, Hattersley A, McCarthy M, et al. Regulation of Fto/Ftm gene expression in mice and humans. Am J Physiol Regul Integr Comp Physiol. 2008;294:R1185-96 pubmed publisher
    ..Animals and humans with various genetic interruptions of FTO or FTM have phenotypes reminiscent of aspects of the Bardet-Biedl obesity syndrome, a confirmed "ciliopathy." FTM has recently been shown to be a ciliary basal body protein...
  5. Zhang S, Kim K, Rosén A, Smyth J, Sakuma R, Delgado Olguin P, et al. Iroquois homeobox gene 3 establishes fast conduction in the cardiac His-Purkinje network. Proc Natl Acad Sci U S A. 2011;108:13576-81 pubmed publisher
    ..Here we show that Iroquois homeobox gene 3 (Irx3) is critical for efficient conduction in this specialized tissue by antithetically regulating two gap junction-..
  6. Houweling A, Dildrop R, Peters T, Mummenhoff J, Moorman A, Ruther U, et al. Gene and cluster-specific expression of the Iroquois family members during mouse development. Mech Dev. 2001;107:169-74 pubmed
    ..of the murine family were found to be organized in two cognate clusters of three genes each, Irx1, -2, -4 and Irx3, -5, -6, respectively (Peters et al., 2000)...
  7. van Tuyl M, Liu J, Groenman F, Ridsdale R, Han R, Venkatesh V, et al. Iroquois genes influence proximo-distal morphogenesis during rat lung development. Am J Physiol Lung Cell Mol Physiol. 2006;290:L777-L789 pubmed
    ..Collectively, these results suggest that Irx genes are involved in the regulation of proximo-distal morphogenesis of the developing lung but are likely not linked to the FGF, BMP, or Shh signaling pathways. ..
  8. Gaborit N, Sakuma R, Wylie J, Kim K, Zhang S, Hui C, et al. Cooperative and antagonistic roles for Irx3 and Irx5 in cardiac morphogenesis and postnatal physiology. Development. 2012;139:4007-19 pubmed publisher
    ..for certain postnatal cardiac functions, including cardiac repolarization (Irx5) and rapid ventricular conduction (Irx3). Irx genes are expressed in dynamic and partially overlapping patterns in the developing heart...
  9. Yeung J, Ha T, Swanson D, Goldowitz D. A Novel and Multivalent Role of Pax6 in Cerebellar Development. J Neurosci. 2016;36:9057-69 pubmed publisher
    ..The present study shows how Pax6 is key to the development of glutamatergic cells in the cerebellum. ..

More Information


  1. Li J, Miao L, Shieh D, Spiotto E, Li J, Zhou B, et al. Single-Cell Lineage Tracing Reveals that Oriented Cell Division Contributes to Trabecular Morphogenesis and Regional Specification. Cell Rep. 2016;15:158-170 pubmed publisher
    ..Furthermore, N-Cadherin deletion in labeled clones disrupted the clonal patterns. In summary, our data demonstrate that OCD contributes to trabecular morphogenesis and specification. ..
  2. Scardigli R, Schuurmans C, Gradwohl G, Guillemot F. Crossregulation between Neurogenin2 and pathways specifying neuronal identity in the spinal cord. Neuron. 2001;31:203-17 pubmed
    ..Thus, neuronal differentiation involves crossregulatory interactions between a bHLH-driven program of neurogenesis and genetic pathways specifying progenitor and neuronal identity in the spinal cord. ..
  3. Vierkotten J, Dildrop R, Peters T, Wang B, Ruther U. Ftm is a novel basal body protein of cilia involved in Shh signalling. Development. 2007;134:2569-77 pubmed
    ..Furthermore, the absence of Ftm in arthropods underlines the divergence between vertebrate and Drosophila Hh pathways...
  4. Sun T, Hafler B, Kaing S, Kitada M, Ligon K, Widlund H, et al. Evidence for motoneuron lineage-specific regulation of Olig2 in the vertebrate neural tube. Dev Biol. 2006;292:152-64 pubmed
    ..Our findings indicate complex regulation of Olig2 by stage- and lineage-specific regulatory elements. They further suggest that transcriptional regulation of Olig2 is involved in segregation of pMN neuroblasts. ..
  5. Lebel M, Agarwal P, Cheng C, Kabir M, Chan T, Thanabalasingham V, et al. The Iroquois homeobox gene Irx2 is not essential for normal development of the heart and midbrain-hindbrain boundary in mice. Mol Cell Biol. 2003;23:8216-25 pubmed
    ..Further studies of mutant mice of other Irx genes as well as compound mutant mice will be necessary to uncover the functional roles of these evolutionarily conserved transcriptional regulators in development and disease. ..
  6. Bell S, Schreiner C, Wert S, Mucenski M, Scott W, Whitsett J. R-spondin 2 is required for normal laryngeal-tracheal, lung and limb morphogenesis. Development. 2008;135:1049-58 pubmed publisher
    ..reduced branching, a reduction in TOPGAL reporter activity, and reduced expression of the downstream Wnt target Irx3. Interbreeding the Rspo2(Tg) and Lrp6(-) alleles resulted in more severe defects consisting of marked lung ..
  7. 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. ..
  8. 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. ..
  9. Smemo S, Tena J, Kim K, Gamazon E, Sakabe N, G mez Mar n C, et al. Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature. 2014;507:371-5 pubmed publisher
    ..noncoding sequences within FTO are functionally connected, at megabase distances, with the homeobox gene IRX3. The obesity-associated FTO region directly interacts with the promoters of IRX3 as well as FTO in the human, mouse ..
  10. Zhulyn O, Li D, Deimling S, Vakili N, Mo R, Puviindran V, et al. A switch from low to high Shh activity regulates establishment of limb progenitors and signaling centers. Dev Cell. 2014;29:241-9 pubmed publisher
  11. Cohen D, Cheng C, Cheng S, Hui C. Expression of two novel mouse Iroquois homeobox genes during neurogenesis. Mech Dev. 2000;91:317-21 pubmed
    ..Three mouse Irx genes, Irx1, Irx2 and Irx3, have been previously identified and are expressed with distinct spatio-temporal patterns during neurogenesis...
  12. Christoffels V, Keijser A, Houweling A, Clout D, Moorman A. Patterning the embryonic heart: identification of five mouse Iroquois homeobox genes in the developing heart. Dev Biol. 2000;224:263-74 pubmed
    ..b>Irx3 was found to be expressed specifically in the trabeculated myocardium of the ventricles...
  13. Takata N, Sakakura E, Sasai Y. IGF-2/IGF-1R signaling has distinct effects on Sox1, Irx3, and Six3 expressions during ES cell derived-neuroectoderm development in vitro. In Vitro Cell Dev Biol Anim. 2016;52:607-15 pubmed publisher
    ..cell lines and we found that the IGF-2/IGF-1R signaling upregulated the expression of the posterior neural marker Irx3. In contrast, the anterior neural marker Six3 was downregulated by IGF-2/IGF-1R signaling...
  14. Kim K, Rosén A, Hussein S, Puviindran V, Korogyi A, Chiarello C, et al. Irx3 is required for postnatal maturation of the mouse ventricular conduction system. Sci Rep. 2016;6:19197 pubmed publisher
    ..We have previously established that the Irx3 homeobox gene regulates rapid electrical propagation in the VCS by modulating the transcription of gap junction ..
  15. Wang B, Weidenfeld J, Lu M, Maika S, Kuziel W, Morrisey E, et al. Foxp1 regulates cardiac outflow tract, endocardial cushion morphogenesis and myocyte proliferation and maturation. Development. 2004;131:4477-87 pubmed
  16. Song M, Sun Y, Bryson A, Gill G, Evans S, Pfaff S. Islet-to-LMO stoichiometries control the function of transcription complexes that specify motor neuron and V2a interneuron identity. Development. 2009;136:2923-32 pubmed publisher
  17. Bellefroid E, Kobbe A, Gruss P, Pieler T, Gurdon J, Papalopulu N. Xiro3 encodes a Xenopus homolog of the Drosophila Iroquois genes and functions in neural specification. EMBO J. 1998;17:191-203 pubmed
    We have identified in Xenopus and in the mouse two highly related genes, Xiro3 and Irx3 respectively, that encode a Drosophila Iroquois-related homeobox transcription factor...
  18. Shekhar A, Lin X, Liu F, Zhang J, Mo H, Bastarache L, et al. Transcription factor ETV1 is essential for rapid conduction in the heart. J Clin Invest. 2016;126:4444-4459 pubmed publisher
    ..Together, these results identify ETV1 as a critical factor in determining fast conduction physiology in the heart. ..
  19. Murdoch J, Doudney K, Gerrelli D, Wortham N, Paternotte C, Stanier P, et al. Genomic organization and embryonic expression of Igsf8, an immunoglobulin superfamily member implicated in development of the nervous system and organ epithelia. Mol Cell Neurosci. 2003;22:62-74 pubmed
    ..Igsf8 is also expressed in the branchial arches, dorsal pancreatic primordium, neural retina, olfactory epithelium, gut, kidney, and lung. ..
  20. Liguori G, Echevarria D, Improta R, Signore M, Adamson E, Martinez S, et al. Anterior neural plate regionalization in cripto null mutant mouse embryos in the absence of node and primitive streak. Dev Biol. 2003;264:537-49 pubmed
    ..These results suggest that, in mouse embryos, the specification of the anterior neural identities can be maintained without an absolute requirement for the embryonic mesoderm and the node. ..
  21. Kim B, Kim Y, Cooke P, Ruther U, Jorgensen J. The fused toes locus is essential for somatic-germ cell interactions that foster germ cell maturation in developing gonads in mice. Biol Reprod. 2011;84:1024-32 pubmed publisher
    ..Previously, we discovered that Irx3 expression was localized specifically to female gonads during embryonic development; therefore, we sought to ..
  22. Sugimori M, Nagao M, Bertrand N, Parras C, Guillemot F, Nakafuku M. Combinatorial actions of patterning and HLH transcription factors in the spatiotemporal control of neurogenesis and gliogenesis in the developing spinal cord. Development. 2007;134:1617-29 pubmed
    ..We propose a molecular code model whereby the combinatorial actions of two classes of transcription factors coordinately regulate the domain-specific temporal sequence of neurogenesis and gliogenesis in the developing spinal cord. ..
  23. Bosse A, Stoykova A, Nieselt Struwe K, Chowdhury K, Copeland N, Jenkins N, et al. Identification of a novel mouse Iroquois homeobox gene, Irx5, and chromosomal localisation of all members of the mouse Iroquois gene family. Dev Dyn. 2000;218:160-74 pubmed
    ..Together, with the data obtained from the chromosomal mapping analysis, the results indicate that these genes have appeared in vertebrates during evolution as a result of gene duplication. ..
  24. Padua M, Fox S, Jiang T, Morse D, Tevosian S. Simultaneous gene deletion of gata4 and gata6 leads to early disruption of follicular development and germ cell loss in the murine ovary. Biol Reprod. 2014;91:24 pubmed publisher
    ..the ovary results in a strong down-regulation of genes involved in the ovarian developmental pathway (Fst and Irx3) as well as diminished expression of the pregranulosa and granulosa cell markers SPRR2 and FOXL2, respectively...
  25. McDonald L, Gerrelli D, Fok Y, Hurst L, Tickle C. Comparison of Iroquois gene expression in limbs/fins of vertebrate embryos. J Anat. 2010;216:683-91 pubmed publisher
    ..In zebrafish, Irx genes of all but six of the families are expressed in early stage pectoral fin buds but not at later stages, suggesting that these genes are not involved in patterning distal structures in zebrafish fins. ..
  26. Paschaki M, Lin S, Wong R, Finnell R, Dolle P, Niederreither K. Retinoic acid-dependent signaling pathways and lineage events in the developing mouse spinal cord. PLoS ONE. 2012;7:e32447 pubmed publisher
  27. Wataya T, Ando S, Muguruma K, Ikeda H, Watanabe K, Eiraku M, et al. Minimization of exogenous signals in ES cell culture induces rostral hypothalamic differentiation. Proc Natl Acad Sci U S A. 2008;105:11796-801 pubmed publisher
    ..These findings indicate that, instead of the addition of inductive signals, minimization of exogenous patterning signaling plays a key role in rostral hypothalamic specification of neural progenitors derived from pluripotent cells. ..
  28. Sirbu I, Gresh L, Barra J, Duester G. Shifting boundaries of retinoic acid activity control hindbrain segmental gene expression. Development. 2005;132:2611-22 pubmed
    ..These two pulses of RA activity function to establish expression of Hoxb1 and vHnf1 on opposite sides of the r4/r5 boundary. ..
  29. Yan Y, Sabharwal P, Rao M, Sockanathan S. The antioxidant enzyme Prdx1 controls neuronal differentiation by thiol-redox-dependent activation of GDE2. Cell. 2009;138:1209-21 pubmed publisher
    ..These findings define Prdx1 as a pivotal regulator of GDE2 activity and suggest roles for coupled thiol-redox-dependent cascades in controlling neuronal differentiation in the spinal cord. ..
  30. Naillat F, Prunskaite Hyyryläinen R, Pietilä I, Sormunen R, Jokela T, Shan J, et al. Wnt4/5a signalling coordinates cell adhesion and entry into meiosis during presumptive ovarian follicle development. Hum Mol Genet. 2010;19:1539-50 pubmed publisher
    ..ovary, in fact, rescues the female property to a certain degree, as seen by inhibition of Cyp26b1 and induction of Irx3 gene expression...
  31. Dykes I, Tempest L, Lee S, Turner E. Brn3a and Islet1 act epistatically to regulate the gene expression program of sensory differentiation. J Neurosci. 2011;31:9789-99 pubmed publisher
  32. Morales D, Hatten M. Molecular markers of neuronal progenitors in the embryonic cerebellar anlage. J Neurosci. 2006;26:12226-36 pubmed
    ..These results identify molecular pathways that offer new insights on the development of the nuclear and cortical structures of the cerebellum, as well as components of the cerebellar circuitry. ..
  33. Satoh K, Kasai M, Ishidao T, Tago K, Ohwada S, Hasegawa Y, et al. Anteriorization of neural fate by inhibitor of beta-catenin and T cell factor (ICAT), a negative regulator of Wnt signaling. Proc Natl Acad Sci U S A. 2004;101:8017-21 pubmed
    ..These results suggest that ICAT plays an important role in the anteriorization of neural cells by inhibiting the posteriorizing activity of Wnt signaling. ..
  34. Götz K, Briscoe J, Ruther U. Homozygous Ft embryos are affected in floor plate maintenance and ventral neural tube patterning. Dev Dyn. 2005;233:623-30 pubmed
  35. 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. ..
  36. Tai G, Hohenstein P, Davies J. FAK-Src signalling is important to renal collecting duct morphogenesis: discovery using a hierarchical screening technique. Biol Open. 2013;2:416-23 pubmed publisher
    ..We demonstrate the utility of the screen by using it to identify the FAK-Src-pathway signalling as being important for collecting duct development, specifically for the cell proliferation on which this development depends. ..
  37. Takata N, Sakakura E, Eiraku M, Kasukawa T, Sasai Y. Self-patterning of rostral-caudal neuroectoderm requires dual role of Fgf signaling for localized Wnt antagonism. Nat Commun. 2017;8:1339 pubmed publisher
    ..embryonic stem cell (ESC), we report that ESC-derived neuroectoderm self-generates a Six3+ rostral and a Irx3+ caudal bipolarized patterning...
  38. Chen J, Huang Y, Mazzoni E, Tan G, Zavadil J, Wichterle H. Mir-17-3p controls spinal neural progenitor patterning by regulating Olig2/Irx3 cross-repressive loop. Neuron. 2011;69:721-35 pubmed publisher
    ..neurons (pMN) and V2 interneurons (p2) are specified by a pair of cross-repressive transcription factors, Olig2 and Irx3. Lineage tracing revealed that many p2 progenitors transiently express the pMN marker Olig2 during spinal cord ..
  39. Kim B, Kim Y, Sakuma R, Hui C, Ruther U, Jorgensen J. Primordial germ cell proliferation is impaired in Fused Toes mutant embryos. Dev Biol. 2011;349:417-26 pubmed publisher
    ..5. The six genes within the Ft locus include the IrxB cluster (Irx3, -5, -6), Fts, Ftm, and Fto, of which only Ftm, Fto, and Fts are expressed in primordial germ cells of the early ..
  40. 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. ..
  41. Moorman A, Houweling A, de Boer P, Christoffels V. Sensitive nonradioactive detection of mRNA in tissue sections: novel application of the whole-mount in situ hybridization protocol. J Histochem Cytochem. 2001;49:1-8 pubmed
    ..The radioactive ISH procedure scarcely permitted detection of these sequences, underscoring the value of this novel method. ..
  42. Combes A, Bowles J, Feng C, Chiu H, Khoo P, Jackson A, et al. Expression and functional analysis of Dkk1 during early gonadal development. Sex Dev. 2011;5:124-30 pubmed publisher
    ..Nor did we find significant differences in expression of key markers of testis and ovarian development. We propose that DKK1 may play a protective role that is not unmasked by loss-of-function in the absence of other stressors. ..
  43. Oh S, Huang X, Liu J, Litingtung Y, Chiang C. Shh and Gli3 activities are required for timely generation of motor neuron progenitors. Dev Biol. 2009;331:261-9 pubmed publisher
  44. Reggiani L, Raciti D, Airik R, Kispert A, Brändli A. The prepattern transcription factor Irx3 directs nephron segment identity. Genes Dev. 2007;21:2358-70 pubmed
    ..To date, the genetic basis of regionalization of the nephron has remained largely unknown. Here we show that Irx3, a member of the Iroquois (Irx) gene family, acts as a master regulator of intermediate tubule fate...
  45. Potter S, Hartman H, Kwan K, Behringer R, Patterson L. Laser capture-microarray analysis of Lim1 mutant kidney development. Genesis. 2007;45:432-9 pubmed
    ..It is interesting to note that Lim1 and Dkk1 mutant mice have striking similarities in phenoytpe. These results suggest that the Dkk1 gene might be a key downstream effector of Lim1 function. ..
  46. Jorgensen J, Gao L. Irx3 is differentially up-regulated in female gonads during sex determination. Gene Expr Patterns. 2005;5:756-62 pubmed
    b>Irx3 is a member of the Iroquois homeobox gene family that encodes a protein known for its essential role in spinal cord development. Transcript screening of male and female gonads during the critical period of sex determination (E12-13...
  47. Peters T, Ausmeier K, Dildrop R, Ruther U. The mouse Fused toes (Ft) mutation is the result of a 1.6-Mb deletion including the entire Iroquois B gene cluster. Mamm Genome. 2002;13:186-8 pubmed
    ..6 Mb of genomic sequences on mouse Chromosome 8. Owing to this deletion, six genes, including the entire IroquoisB (IrxB) gene cluster, are directly affected by the Ft mutation. ..
  48. 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
  49. Peters T, Dildrop R, Ausmeier K, Ruther U. Organization of mouse Iroquois homeobox genes in two clusters suggests a conserved regulation and function in vertebrate development. Genome Res. 2000;10:1453-62 pubmed
    ..The maintenance of two cognate Irx gene clusters during vertebrate evolution suggests that their genomic organization is important for the regulation, expression, and function of Irx genes during embryonic development. ..
  50. Yokoyama S, Furukawa S, Kitada S, Mori M, Saito T, Kawakami K, et al. Analysis of transcription factors expressed at the anterior mouse limb bud. PLoS ONE. 2017;12:e0175673 pubmed publisher
    ..5-E11.5 limb bud. Among these genes, Irx3 showed a posteriorly expanded expression domain in Shh-/- limb buds and an anteriorly reduced expression domain in ..
  51. Basta J, Robbins L, Denner D, Kolar G, Rauchman M. A Sall1-NuRD interaction regulates multipotent nephron progenitors and is required for loop of Henle formation. Development. 2017;144:3080-3094 pubmed publisher
    ..These findings highlight an important function of Sall1-NuRD interaction in the regulation of Six2-positive multipotent renal progenitor cells and formation of the loop of Henle. ..
  52. Mahlapuu M, Ormestad M, Enerback S, Carlsson P. The forkhead transcription factor Foxf1 is required for differentiation of extra-embryonic and lateral plate mesoderm. Development. 2001;128:155-66 pubmed
    ..Expression of Foxf1 and the homeobox gene Irx3 defines the splanchnic and somatic mesodermal layers, respectively...
  53. Briscoe J, Pierani A, Jessell T, Ericson J. A homeodomain protein code specifies progenitor cell identity and neuronal fate in the ventral neural tube. Cell. 2000;101:435-45 pubmed
    ..The combinatorial expression of three of these proteins--Nkx6.1, Nkx2.2, and Irx3--specifies the identity of three classes of neurons generated in the ventral third of the neural tube.