Gene Symbol: Hmx3
Description: H6 homeobox 3
Alias: Nkx-5.1, Nkx5-1, Nkx5.1, homeobox protein HMX3, H6 homeo box 3, homeobox protein H6 family member 3, homeobox protein Nkx-5.1
Species: mouse
Products:     Hmx3

Top Publications

  1. Lin Z, Cantos R, Patente M, Wu D. Gbx2 is required for the morphogenesis of the mouse inner ear: a downstream candidate of hindbrain signaling. Development. 2005;132:2309-18 pubmed
    ..However, Gbx2 promotes ventral fates such as the saccule and cochlear duct, possibly by restricting Otx2 expression...
  2. 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
  3. Zheng W, Huang L, Wei Z, Silvius D, Tang B, Xu P. The role of Six1 in mammalian auditory system development. Development. 2003;130:3989-4000 pubmed
    ..These analyses establish a role for Six1 in early growth and patterning of the otic vesicle. ..
  4. Somma G, Alger H, McGuire R, Kretlow J, Ruiz F, Yatsenko S, et al. Head bobber: an insertional mutation causes inner ear defects, hyperactive circling, and deafness. J Assoc Res Otolaryngol. 2012;13:335-49 pubmed publisher
    ..We propose that genes critical for inner ear patterning and differentiation are lost at the head bobber locus and are candidate genes for human deafness and vestibular disorders. ..
  5. Riccomagno M, Takada S, Epstein D. Wnt-dependent regulation of inner ear morphogenesis is balanced by the opposing and supporting roles of Shh. Genes Dev. 2005;19:1612-23 pubmed
    ..The restriction of Wnt target genes to the dorsal otocyst is also influenced by Shh. Thus, a balance between Wnt and Shh signaling activities is key in distinguishing between vestibular and auditory cell types. ..
  6. Wang W, Lo P, Frasch M, Lufkin T. Hmx: an evolutionary conserved homeobox gene family expressed in the developing nervous system in mice and Drosophila. Mech Dev. 2000;99:123-37 pubmed
    Three homeobox genes, one from Drosophila melanogaster (Drosophila Hmx gene) and two from mouse (murine Hmx2 and Hmx3) were isolated and the full-length cDNAs and corresponding genomic structures were characterized...
  7. Ozaki H, Nakamura K, Funahashi J, Ikeda K, Yamada G, Tokano H, et al. Six1 controls patterning of the mouse otic vesicle. Development. 2004;131:551-62 pubmed
    ..were expressed ventrally in the wild-type otic vesicles, were abolished, while the expression domains of Dlx5, Hmx3, Dach1 and Dach2, which were expressed dorsally in the wild-type otic vesicles, expanded ventrally...
  8. Hulander M, Kiernan A, Blomqvist S, Carlsson P, Samuelsson E, Johansson B, et al. Lack of pendrin expression leads to deafness and expansion of the endolymphatic compartment in inner ears of Foxi1 null mutant mice. Development. 2003;130:2013-25 pubmed
    ..Thus, mutations in FOXI1 could prove to cause a Pendred syndrome-like human deafness...
  9. Wang W, Chan E, Baron S, Van de Water T, Lufkin T. Hmx2 homeobox gene control of murine vestibular morphogenesis. Development. 2001;128:5017-29 pubmed
    ..Hmx2, a member of the Hmx homeobox gene family, is coexpressed with Hmx3 in the dorsolateral otic epithelium...

More Information


  1. Robledo R, Lufkin T. Dlx5 and Dlx6 homeobox genes are required for specification of the mammalian vestibular apparatus. Genesis. 2006;44:425-37 pubmed
    ..Given their proximity to the disease locus and the observed phenotype in Dlx5/6 null mice, Dlx5/6 are likely candidates to mediate the inner ear defects observed in patients with split hand/split foot malformation. ..
  2. Rinkwitz Brandt S, Arnold H, Bober E. Regionalized expression of Nkx5-1, Nkx5-2, Pax2 and sek genes during mouse inner ear development. Hear Res. 1996;99:129-38 pubmed
    ..In the vestibulum Pax2 and sek is limited to the ventral part whereas Nkx5 genes are active throughout. These data suggest that Nkx5 genes, Pax2 and sek play different roles in the patterning of inner ear structures. ..
  3. Hadrys T, Braun T, Rinkwitz Brandt S, Arnold H, Bober E. Nkx5-1 controls semicircular canal formation in the mouse inner ear. Development. 1998;125:33-9 pubmed
    ..Nkx5-1 is the first ear-specific molecule identified to play a crucial role in the formation of the mammalian vestibular system. ..
  4. 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. ..
  5. Chang W, Lin Z, Kulessa H, Hebert J, Hogan B, Wu D. Bmp4 is essential for the formation of the vestibular apparatus that detects angular head movements. PLoS Genet. 2008;4:e1000050 pubmed publisher
    ..Our results suggest that, in comparison to sensory bristles, crista formation within the inner ear requires an additional step of sensory and non-sensory fate specification...
  6. Salminen M, Meyer B, Bober E, Gruss P. Netrin 1 is required for semicircular canal formation in the mouse inner ear. Development. 2000;127:13-22 pubmed
  7. Zou D, Silvius D, Rodrigo Blomqvist S, Enerback S, Xu P. Eya1 regulates the growth of otic epithelium and interacts with Pax2 during the development of all sensory areas in the inner ear. Dev Biol. 2006;298:430-41 pubmed
  8. Wang W, Grimmer J, Van De Water T, Lufkin T. Hmx2 and Hmx3 homeobox genes direct development of the murine inner ear and hypothalamus and can be functionally replaced by Drosophila Hmx. Dev Cell. 2004;7:439-53 pubmed
    ..Here, we show that murine Hmx2 and Hmx3 have both overlapping and distinct functions in the development of the inner ear's vestibular system, whereas their ..
  9. Bober E, Baum C, Braun T, Arnold H. A novel NK-related mouse homeobox gene: expression in central and peripheral nervous structures during embryonic development. Dev Biol. 1994;162:288-303 pubmed
    ..The time pattern of Nkx-5.1 expression and its confinement to primarily postmitotic cells of the central and peripheral nervous system suggest that Nkx-5.1 may play a role in the specification of neuronal cell types. ..
  10. Deng M, Pan L, Xie X, Gan L. Differential expression of LIM domain-only (LMO) genes in the developing mouse inner ear. Gene Expr Patterns. 2006;6:857-63 pubmed
    ..Thus, the regionalized expression patterns of LMO1-4 are closely associated with the morphogenesis of the inner ear. ..
  11. Merlo G, Paleari L, Mantero S, Zerega B, Adamska M, Rinkwitz S, et al. The Dlx5 homeobox gene is essential for vestibular morphogenesis in the mouse embryo through a BMP4-mediated pathway. Dev Biol. 2002;248:157-69 pubmed
    ..In the Dlx5(-/-) embryos, no changes in expression of Nkx5.1(Hmx3), Pax2, and Lfng have been seen, while expression of bone morphogenetic protein-4 (Bmp4) was drastically reduced...
  12. Acampora D, Merlo G, Paleari L, Zerega B, Postiglione M, Mantero S, et al. Craniofacial, vestibular and bone defects in mice lacking the Distal-less-related gene Dlx5. Development. 1999;126:3795-809 pubmed
    ..The defects observed in Dlx5-/- mutant animals suggest multiple and independent roles of this gene in the patterning of the branchial arches, in the morphogenesis of the vestibular organ and in osteoblast differentiation. ..
  13. Wang W, Van de Water T, Lufkin T. Inner ear and maternal reproductive defects in mice lacking the Hmx3 homeobox gene. Development. 1998;125:621-34 pubmed
    ..The three members of the murine Hmx family, designated Hmx1, Hmx2 and Hmx3, are expressed in tissues that suggest a common functional role in sensory organ development and pregnancy...
  14. Xu S, Ladak R, Swanson D, Soltyk A, Sun H, Ploder L, et al. PHR1 encodes an abundant, pleckstrin homology domain-containing integral membrane protein in the photoreceptor outer segments. J Biol Chem. 1999;274:35676-85 pubmed
    ..This activity and subcellular location suggests that PHR1 may function as a previously unrecognized modulator of the phototransduction pathway. ..
  15. Mennerich D, Hoffmann S, Hadrys T, Arnold H, Bober E. Two highly related homeodomain proteins, Nkx5-1 and Nkx5-2, display different DNA binding specificities. Biol Chem. 1999;380:1041-8 pubmed
    ..An additional, novel and unrelated high affinity binding sequence could be identified for the Nkx5-2 protein. ..
  16. Ohuchi H, Yasue A, Ono K, Sasaoka S, Tomonari S, Takagi A, et al. Identification of cis-element regulating expression of the mouse Fgf10 gene during inner ear development. Dev Dyn. 2005;233:177-87 pubmed
    ..Furthermore, the analysis of a putative inner ear enhancer of Fgf10 has disclosed a complicated regulation of Fgf10 during inner ear development by numerous transcription factors and signaling pathways. ..
  17. Hatch E, Noyes C, Wang X, Wright T, Mansour S. Fgf3 is required for dorsal patterning and morphogenesis of the inner ear epithelium. Development. 2007;134:3615-25 pubmed
    ..Finally, we show that Fgf3 prevents ventral expansion of r5-6 neurectodermal Wnt3a, serving to focus inductive WNT signals on the dorsal otic vesicle and highlighting a new example of cross-talk between the two signaling systems. ..
  18. Jayasena C, Ohyama T, Segil N, Groves A. Notch signaling augments the canonical Wnt pathway to specify the size of the otic placode. Development. 2008;135:2251-61 pubmed publisher
  19. Abraira V, Del Rio T, Tucker A, Slonimsky J, Keirnes H, Goodrich L. Cross-repressive interactions between Lrig3 and netrin 1 shape the architecture of the inner ear. Development. 2008;135:4091-9 pubmed publisher
    ..Thus, the Lrig3/Ntn1 feedback loop dictates when and where basement membrane breakdown occurs during canal development, revealing a new mechanism of complex tissue morphogenesis. ..
  20. Rhinn M, Schuhbaur B, Niederreither K, Dolle P. Involvement of retinol dehydrogenase 10 in embryonic patterning and rescue of its loss of function by maternal retinaldehyde treatment. Proc Natl Acad Sci U S A. 2011;108:16687-92 pubmed publisher
    ..These results underscore the importance of maternal retinoids in preventing congenital birth defects, and lead to a revised model of the importance of RDH10 and RALDHs in controlling embryonic RA distribution...
  21. Steffes G, Lorente Cánovas B, Pearson S, Brooker R, Spiden S, Kiernan A, et al. Mutanlallemand (mtl) and Belly Spot and Deafness (bsd) are two new mutations of Lmx1a causing severe cochlear and vestibular defects. PLoS ONE. 2012;7:e51065 pubmed publisher
    ..We have found that these mutants develop sensory patches although they are misshapen. The characterization of these two new Lmx1a alleles highlights the critical role of this gene in the development of the cochlea and vestibular system. ..
  22. Espinosa Medina I, Saha O, Boismoreau F, Chettouh Z, Rossi F, Richardson W, et al. The sacral autonomic outflow is sympathetic. Science. 2016;354:893-897 pubmed
    ..This simplified, bipartite architecture offers a new framework to understand pelvic neurophysiology as well as development and evolution of the autonomic nervous system. ..
  23. Stadler H, Murray J, Leysens N, Goodfellow P, Solursh M. Phylogenetic conservation and physical mapping of members of the H6 homeobox gene family. Mamm Genome. 1995;6:383-8 pubmed
    ..melanogaster (fruit fly). ..
  24. Romand R, Albuisson E, Niederreither K, Fraulob V, Chambon P, Dolle P. Specific expression of the retinoic acid-synthesizing enzyme RALDH2 during mouse inner ear development. Mech Dev. 2001;106:185-9 pubmed
    ..Raldh2 mesenchymal expression did not correlate with migrating neural crest-derived melanoblasts. These restricted expression domains may correspond to specific sites of RA synthesis during inner ear morphogenesis. ..
  25. Wang W, Lufkin T. Assignment of the murine Hmx2 and Hmx3 homeobox genes to the distal region of mouse chromosome 7. Chromosome Res. 1997;5:501-2 pubmed
  26. Bulfone A, Gattuso C, Marchitiello A, Pardini C, Boncinelli E, Borsani G, et al. The embryonic expression pattern of 40 murine cDNAs homologous to Drosophila mutant genes (Dres): a comparative and topographic approach to predict gene function. Hum Mol Genet. 1998;7:1997-2006 pubmed
    ..Furthermore, the information derived from this combined approach will be instrumental in predicting the phenotypic consequences of gene dysfunction in both mouse mutants and human genetic diseases. ..
  27. Moraes F, Novoa A, Jerome Majewska L, Papaioannou V, Mallo M. Tbx1 is required for proper neural crest migration and to stabilize spatial patterns during middle and inner ear development. Mech Dev. 2005;122:199-212 pubmed
    ..The inability of the Tbx1(-/-) embryos to keep properly segregated functional domains in the otocyst is likely the cause of the strong inner ear phenotypes observed in these mutants. ..
  28. Puelles L, Morales Delgado N, Merchán P, Castro Robles B, Martínez de la Torre M, Díaz C, et al. Radial and tangential migration of telencephalic somatostatin neurons originated from the mouse diagonal area. Brain Struct Funct. 2016;221:3027-65 pubmed publisher
    ..5 onward, comparing their topography with the expression patterns of the genes Dlx5, Gbx2, Lhx7-8, Nkx2.1, Nkx5.1 (Hmx3), and Shh, which variously label parts of the subpallium...
  29. Buniello A, Hardisty Hughes R, Pass J, Bober E, Smith R, Steel K. Headbobber: a combined morphogenetic and cochleosaccular mouse model to study 10qter deletions in human deafness. PLoS ONE. 2013;8:e56274 pubmed publisher
    ..long range effect of the deletion on the expression of neighboring genes on Chr7, associated with downregulation of Hmx3, Hmx2 and Nkx1.2 homeobox transcription factors...
  30. Rinkwitz Brandt S, Justus M, Oldenettel I, Arnold H, Bober E. Distinct temporal expression of mouse Nkx-5.1 and Nkx-5.2 homeobox genes during brain and ear development. Mech Dev. 1995;52:371-81 pubmed
    ..The same expression domains also exist for Nkx-5.2 beginning at E13.5. The regionally restricted expression pattern of both Nkx-5 genes during mouse development suggests their involvement in cell type specification of neuronal cells. ..
  31. Amendt B, Sutherland L, Russo A. Transcriptional antagonism between Hmx1 and Nkx2.5 for a shared DNA-binding site. J Biol Chem. 1999;274:11635-42 pubmed
    ..In this report, we have identified the preferred DNA-binding site of the murine Hmx3 homeodomain protein by the selection and amplification binding (SAAB) technique...
  32. Deng M, Pan L, Xie X, Gan L. Requirement for Lmo4 in the vestibular morphogenesis of mouse inner ear. Dev Biol. 2010;338:38-49 pubmed publisher
  33. Nelms K, O Neill T, Li S, Hubbard S, Gustafson T, Paul W. Alternative splicing, gene localization, and binding of SH2-B to the insulin receptor kinase domain. Mamm Genome. 1999;10:1160-7 pubmed
    ..Additionally, the chromosomal location of the SH2-B gene was determined to be the distal arm of mouse Chromosome (Chr) 7 in a region linked to obesity in mice. ..
  34. Fowler K, Kalitsis P, Choo K. Mouse mitotic spindle checkpoint Bub3 gene maps to the distal region of chromosome 7 by interspecific backcross analysis. Cytogenet Cell Genet. 1999;87:91-2 pubmed
  35. 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. ..
  36. McNay D, Pelling M, Claxton S, Guillemot F, Ang S. Mash1 is required for generic and subtype differentiation of hypothalamic neuroendocrine cells. Mol Endocrinol. 2006;20:1623-32 pubmed
    ..These data demonstrate that Mash1 is both required for the generation of ventral neuroendocrine neurons as well as playing a central role in subtype specification of these neurons. ..
  37. Pelling M, Anthwal N, McNay D, Gradwohl G, Leiter A, Guillemot F, et al. Differential requirements for neurogenin 3 in the development of POMC and NPY neurons in the hypothalamus. Dev Biol. 2011;349:406-16 pubmed publisher
    ..Given the opposing roles of POMC and NPY neurons in regulating food intake, these results indicate that Ngn3 plays a central role in the generation of neuronal populations controlling energy homeostasis in mice. ..
  38. Urness L, Paxton C, Wang X, Schoenwolf G, Mansour S. FGF signaling regulates otic placode induction and refinement by controlling both ectodermal target genes and hindbrain Wnt8a. Dev Biol. 2010;340:595-604 pubmed publisher
    ..Several genes in the down-regulated class, including Hmx3, Hmx2, Foxg1, Sox9, Has2, and Slc26a9 were validated by in situ hybridization...
  39. Hurd E, Micucci J, Reamer E, Martin D. Delayed fusion and altered gene expression contribute to semicircular canal defects in Chd7 deficient mice. Mech Dev. 2012;129:308-23 pubmed publisher aplasia of the semicircular canals and sensory vestibular organs, with reduced or absent expression of Otx1, Hmx3, Jagged1, Lmo4, Msx1 and Sox2...
  40. Niederreither K, Vermot J, Schuhbaur B, Chambon P, Dolle P. Retinoic acid synthesis and hindbrain patterning in the mouse embryo. Development. 2000;127:75-85 pubmed
    ..We conclude that RA produced by the embryo is required to generate posterior cell fates in the developing mouse hindbrain, its absence leading to an abnormal r3 (and, to a lesser extent, r4) identity of the caudal hindbrain cells. ..