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Gene Review

Irx3  -  Iroquois related homeobox 3

Mus musculus

Synonyms: AI894186, Homeodomain protein IRXB1, Iroquois homeobox protein 3, Iroquois-class homeodomain protein IRX-3, Irxb1
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Psychiatry related information on Irx3

  • Transcript screening of male and female gonads during the critical period of sex determination (E12-13.5) revealed a sexually dimorphic expression pattern for Irx3 with female gonads exhibiting a sixfold increase in expression over time [1].

High impact information on Irx3

  • We further show that differential competence of thalamic and prethalamic primordia in responding to Shh signaling is regulated by the transcription factor Irx3 [2].
  • In contrast, hypermethylation of the 5' CpG island region of the homeobox gene Irx3 in TRAMP is associated with reduced gene expression [3].
  • Expression of Foxf1 and the homeobox gene Irx3 defines the splanchnic and somatic mesodermal layers, respectively [4].
  • Irx3 was found to be expressed specifically in the trabeculated myocardium of the ventricles [5].
  • The six members 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) [6].

Anatomical context of Irx3

  • Interestingly, all three iroquois zebrafish genes are expressed in the notochord while only Irx3 is active in the mouse notochord [7].
  • Irx3 is differentially up-regulated in female gonads during sex determination [1].
  • Together, these results suggest that the Irx3 signal is restricted to the somatic cell component of XX gonads and is present at a discreet period of ovarian development that ends abruptly at birth [1].
  • The Irx3 signal persisted in germ cell-depleted XX gonads resulting from Busulfan treatment suggesting that its expression was independent of germ cell regulation [1].
  • Irx3 is a member of the Iroquois homeobox gene family that encodes a protein known for its essential role in spinal cord development [1].

Other interactions of Irx3

  • Three mouse Irx genes, Irx1, Irx2 and Irx3, have been previously identified and are expressed with distinct spatio-temporal patterns during neurogenesis [8].

Analytical, diagnostic and therapeutic context of Irx3

  • Quantitative real-time PCR analysis over an extended time course determined that Irx3 message was low initially and then increased in XX gonads until E13.5, remained elevated until birth, diminished shortly after birth, and remained low in the adult ovary [1].
  • Whole mount in situ hybridization confirmed the sexually dimorphic nature of Irx3 expression and immunohistochemical analysis of gonads at E13.5 determined that IRX3 and GATA4 proteins co-localized to somatic cells of XX gonads [1].


  1. Irx3 is differentially up-regulated in female gonads during sex determination. Jorgensen, J.S., Gao, L. Gene Expr. Patterns (2005) [Pubmed]
  2. Hedgehog signaling from the ZLI regulates diencephalic regional identity. Kiecker, C., Lumsden, A. Nat. Neurosci. (2004) [Pubmed]
  3. DNA methylation pathway alterations in an autochthonous murine model of prostate cancer. Morey, S.R., Smiraglia, D.J., James, S.R., Yu, J., Moser, M.T., Foster, B.A., Karpf, A.R. Cancer Res. (2006) [Pubmed]
  4. The forkhead transcription factor Foxf1 is required for differentiation of extra-embryonic and lateral plate mesoderm. Mahlapuu, M., Ormestad, M., Enerbäck, S., Carlsson, P. Development (2001) [Pubmed]
  5. Patterning the embryonic heart: identification of five mouse Iroquois homeobox genes in the developing heart. Christoffels, V.M., Keijser, A.G., Houweling, A.C., Clout, D.E., Moorman, A.F. Dev. Biol. (2000) [Pubmed]
  6. Gene and cluster-specific expression of the Iroquois family members during mouse development. Houweling, A.C., Dildrop, R., Peters, T., Mummenhoff, J., Moorman, A.F., Rüther, U., Christoffels, V.M. Mech. Dev. (2001) [Pubmed]
  7. Expression of two novel zebrafish iroquois homologues (ziro1 and ziro5) during early development of axial structures and central nervous system. Wang, X., Emelyanov, A., Sleptsova-Friedrich, I., Korzh, V., Gong, Z. Mech. Dev. (2001) [Pubmed]
  8. Expression of two novel mouse Iroquois homeobox genes during neurogenesis. Cohen, D.R., Cheng, C.W., Cheng, S.H., Hui, C.C. Mech. Dev. (2000) [Pubmed]
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