Hoxd11

Summary

Gene Symbol: Hoxd11
Description: homeobox D11
Alias: E230017H14Rik, Hox-4.6, Hox-5.4, Hox-5.5, homeobox protein Hox-D11, homeo box D11, homeobox protein Hox-4.6, homeobox protein Hox-5.5
Species: mouse
Products:     Hoxd11

Top Publications

  1. Kondo T, Duboule D. Breaking colinearity in the mouse HoxD complex. Cell. 1999;97:407-17 pubmed
    ..These data suggest that a regulatory element located upstream of the complex is necessary for setting up the early pattern of Hox gene colinear activation. ..
  2. Zakany J, Gerard M, Favier B, Duboule D. Deletion of a HoxD enhancer induces transcriptional heterochrony leading to transposition of the sacrum. EMBO J. 1997;16:4393-402 pubmed
    ..A slight time delay in expression (transcriptional heterochrony) cannot be compensated for at a later developmental stage, eventually leading to morphological alterations. ..
  3. Buscher D, Bosse B, Heymer J, Ruther U. Evidence for genetic control of Sonic hedgehog by Gli3 in mouse limb development. Mech Dev. 1997;62:175-82 pubmed
    ..This data suggest that Gli3 is a regulator of Shh expression in mouse limb development. ..
  4. Zakany J, Kmita M, Duboule D. A dual role for Hox genes in limb anterior-posterior asymmetry. Science. 2004;304:1669-72 pubmed
    ..a large deficiency in the mouse HoxD cluster, we found that a perturbation in the early collinear expression of Hoxd11, Hoxd12, and Hoxd13 in limb buds led to a loss of asymmetry...
  5. Gerard M, Chen J, Gronemeyer H, Chambon P, Duboule D, Zakany J. In vivo targeted mutagenesis of a regulatory element required for positioning the Hoxd-11 and Hoxd-10 expression boundaries. Genes Dev. 1996;10:2326-34 pubmed
    ..These results illustrate the sharing, in cis, of a single regulatory element in order to establish the expression boundaries of two neighboring Hoxd genes. ..
  6. Kmita M, Fraudeau N, Herault Y, Duboule D. Serial deletions and duplications suggest a mechanism for the collinearity of Hoxd genes in limbs. Nature. 2002;420:145-50 pubmed
  7. Lewandoski M, Sun X, Martin G. Fgf8 signalling from the AER is essential for normal limb development. Nat Genet. 2000;26:460-3 pubmed
    ..Our data identify Fgf8 as the only known AER-Fgf individually necessary for normal limb development, and provide insight into the function of Fgf signalling from the AER in the normal outgrowth and patterning of the limb. ..
  8. Zuniga A, Quillet R, Perrin Schmitt F, Zeller R. Mouse Twist is required for fibroblast growth factor-mediated epithelial-mesenchymal signalling and cell survival during limb morphogenesis. Mech Dev. 2002;114:51-9 pubmed
    ..Finally, Twist function, most likely by regulating FGF signalling, is required for cell survival as apoptotic cells are detected in posterior and distal limb bud mesenchyme. ..
  9. Herault Y, Fraudeau N, Zakany J, Duboule D. Ulnaless (Ul), a regulatory mutation inducing both loss-of-function and gain-of-function of posterior Hoxd genes. Development. 1997;124:3493-500 pubmed

More Information

Publications62

  1. te Welscher P, Zuniga A, Kuijper S, Drenth T, Goedemans H, Meijlink F, et al. Progression of vertebrate limb development through SHH-mediated counteraction of GLI3. Science. 2002;298:827-30 pubmed
    ..Our genetic analysis indicates that SHH signaling counteracts GLI3-mediated repression of key regulator genes, cell survival, and distal progression of limb bud development. ..
  2. Sheth R, Bastida M, Ros M. Hoxd and Gli3 interactions modulate digit number in the amniote limb. Dev Biol. 2007;310:430-41 pubmed
    ..Our results also support the notion that an adequate balance between positive and negative effects of different Hoxd genes is required for pentadactyly. ..
  3. Spitz F, Gonzalez F, Duboule D. A global control region defines a chromosomal regulatory landscape containing the HoxD cluster. Cell. 2003;113:405-17 pubmed
    ..These domains were interrupted in the Ulnaless mutation, a balanced inversion that modified the topography of the locus. We discuss the heuristic value of these results in term of locus specific versus gene-specific regulation. ..
  4. Gerard M, Duboule D, Zakany J. Structure and activity of regulatory elements involved in the activation of the Hoxd-11 gene during late gastrulation. EMBO J. 1993;12:3539-50 pubmed
    ..These results suggest that stage- and tissue-specific cooperation between regulatory elements is required to control properly the activity of the Hoxd-11 promoter. ..
  5. Izpisua Belmonte J, Dolle P, Renucci A, Zappavigna V, Falkenstein H, Duboule D. Primary structure and embryonic expression pattern of the mouse Hox-4.3 homeobox gene. Development. 1990;110:733-45 pubmed
    ..Like other genes of the HOX-4(5) complex, Hox-4.3 is expressed in developing limbs and gonads, suggesting that 'cluster specificity' could be a feature of the HOX network. ..
  6. Davis A, Capecchi M. Axial homeosis and appendicular skeleton defects in mice with a targeted disruption of hoxd-11. Development. 1994;120:2187-98 pubmed
    ..Taken together, these observations suggest an important role for Hox genes in controlling localized growth of those cells that contribute to forming the appendicular skeleton. ..
  7. Barna M, Pandolfi P, Niswander L. Gli3 and Plzf cooperate in proximal limb patterning at early stages of limb development. Nature. 2005;436:277-81 pubmed
    ..The initial division of the vertebrate limb into two distinct molecular domains is consistent with fossil evidence indicating that the upper and lower extremities of the limb have different evolutionary origins. ..
  8. Mugford J, Sipila P, Kobayashi A, Behringer R, McMahon A. Hoxd11 specifies a program of metanephric kidney development within the intermediate mesoderm of the mouse embryo. Dev Biol. 2008;319:396-405 pubmed publisher
    ..Previous studies have shown a requirement for Hox11 paralogs (Hoxa11, Hoxc11 and Hoxd11) in metanephric development. Mice lacking all Hox11 activity fail to form metanephric kidney structures...
  9. Capellini T, Di Giacomo G, Salsi V, Brendolan A, Ferretti E, Srivastava D, et al. Pbx1/Pbx2 requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution and Shh expression. Development. 2006;133:2263-73 pubmed
  10. Hostikka S, Capecchi M. The mouse Hoxc11 gene: genomic structure and expression pattern. Mech Dev. 1998;70:133-45 pubmed
    ..In the hindlimbs, Hoxc11 expression is seen in the mesenchyme posterior to the region forming the femur and fibula, but does not extend anteriorly to the region giving rise to the tibia or distally to the tarsal bones. ..
  11. Wellik D, Hawkes P, Capecchi M. Hox11 paralogous genes are essential for metanephric kidney induction. Genes Dev. 2002;16:1423-32 pubmed
    ..For example, mice individually mutant for Hoxa11 or Hoxd11 show no discernible kidney abnormalities...
  12. Tarchini B, Huynh T, Cox G, Duboule D. HoxD cluster scanning deletions identify multiple defects leading to paralysis in the mouse mutant Ironside. Genes Dev. 2005;19:2862-76 pubmed
    ..These results highlight the importance of a systematic approach when studying such clustered gene families, and give insights into the function and regulation of Hox and Evx2 genes during early spinal cord development. ..
  13. McIntyre D, Rakshit S, Yallowitz A, Loken L, Jeannotte L, Capecchi M, et al. Hox patterning of the vertebrate rib cage. Development. 2007;134:2981-9 pubmed
    ..Thus, the ;Hox code' in somitic mesoderm is the result of the distinct, graded effects of two or more Hox paralogous groups functioning in any anteroposterior location. ..
  14. Panman L, Drenth T, Tewelscher P, Zuniga A, Zeller R. Genetic interaction of Gli3 and Alx4 during limb development. Int J Dev Biol. 2005;49:443-8 pubmed
    ..Most interestingly, the loss of the severe preaxial polydactyly characteristic of Gli3-/- limbs in double mutant embryos establishes that this type of polydactyly requires Alx4 function. ..
  15. Zakany J, Kmita M, Alarcon P, de la Pompa J, Duboule D. Localized and transient transcription of Hox genes suggests a link between patterning and the segmentation clock. Cell. 2001;106:207-17 pubmed
    ..These results suggest a molecular link between Hox gene activation and the segmentation clock. Such a linkage would efficiently keep in phase the production of novel segments with their morphological specification. ..
  16. Davis A, Witte D, Hsieh Li H, Potter S, Capecchi M. Absence of radius and ulna in mice lacking hoxa-11 and hoxd-11. Nature. 1995;375:791-5 pubmed
    ..The appendicular skeleton defects suggest that paralogous Hox genes function together to specify limb outgrowth and patterning along the proximodistal axis. ..
  17. Herault Y, Beckers J, Kondo T, Fraudeau N, Duboule D. Genetic analysis of a Hoxd-12 regulatory element reveals global versus local modes of controls in the HoxD complex. Development. 1998;125:1669-77 pubmed
    ..These results support a model whereby global as well as local regulatory influences are necessary to build up the complex expression patterns of Hoxd genes during limb development. ..
  18. van der Hoeven F, Zakany J, Duboule D. Gene transpositions in the HoxD complex reveal a hierarchy of regulatory controls. Cell. 1996;85:1025-35 pubmed
    ..These results suggest that high order regulation controls the activation of Hox genes and highlight three important constraints responsible for the conservation of Hox gene clustering. ..
  19. Zuniga A, Zeller R. Gli3 (Xt) and formin (ld) participate in the positioning of the polarising region and control of posterior limb-bud identity. Development. 1999;126:13-21 pubmed
    ..Concurrently, Gli3 functions independently of formin during initial posterior nesting of 5'HoxD domains, whereas their subsequent distal restriction and anterior expansion depends on genetic interaction of Gli3 and formin. ..
  20. Izpisua Belmonte J, Falkenstein H, Dolle P, Renucci A, Duboule D. Murine genes related to the Drosophila AbdB homeotic genes are sequentially expressed during development of the posterior part of the body. EMBO J. 1991;10:2279-89 pubmed
    ..Furthermore, the possible role of 'temporal colinearity' in the ontogeny of all coelomic (metamerized) metazoans showing a temporal anteroposterior morphogenetic progression is addressed. ..
  21. Xu B, Wellik D. Axial Hox9 activity establishes the posterior field in the developing forelimb. Proc Natl Acad Sci U S A. 2011;108:4888-91 pubmed publisher
    ..This Hox9 mutant phenotype is restricted to the forelimbs; mutant hindlimbs are normal, revealing fundamental differences in the patterning mechanisms governing the establishment of forelimb and hindlimb fields. ..
  22. Yallowitz A, Gong K, Swinehart I, Nelson L, Wellik D. Non-homeodomain regions of Hox proteins mediate activation versus repression of Six2 via a single enhancer site in vivo. Dev Biol. 2009;335:156-65 pubmed publisher
  23. Chen Y, Knezevic V, Ervin V, Hutson R, Ward Y, Mackem S. Direct interaction with Hoxd proteins reverses Gli3-repressor function to promote digit formation downstream of Shh. Development. 2004;131:2339-47 pubmed
    ..The resulting altered balance between 'effective' Gli3 activating and repressing functions may also serve to extend the Shh activity gradient spatially or temporally...
  24. Boulet A, Capecchi M. Multiple roles of Hoxa11 and Hoxd11 in the formation of the mammalian forelimb zeugopod. Development. 2004;131:299-309 pubmed
    ..Targeted disruption of Hoxa11 and Hoxd11 or Hoxa10, Hoxc10 and Hoxd10 result in gross mispatterning of the radius and ulna or the femur, respectively...
  25. Wellik D, Capecchi M. Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton. Science. 2003;301:363-7 pubmed
    ..The redundancy among these paralogous family members is so great that this global aspect of Hox patterning is not apparent in mice that are mutant for five of the six paralogous alleles. ..
  26. Gong K, Yallowitz A, Sun H, Dressler G, Wellik D. A Hox-Eya-Pax complex regulates early kidney developmental gene expression. Mol Cell Biol. 2007;27:7661-8 pubmed
    ..Thus, anterior-posterior-patterning Hox proteins interact with Pax2 and Eya1, factors important for nephrogenic mesoderm specification, to directly regulate the activation of downstream target genes during early kidney development. ..
  27. Niederreither K, Vermot J, Schuhbaur B, Chambon P, Dolle P. Embryonic retinoic acid synthesis is required for forelimb growth and anteroposterior patterning in the mouse. Development. 2002;129:3563-74 pubmed
    ..We suggest that RA signaling cooperates with a posteriorly restricted factor such as dHand, to generate a functional zone of polarizing activity (ZPA). ..
  28. Zakany J, Duboule D. Synpolydactyly in mice with a targeted deficiency in the HoxD complex. Nature. 1996;384:69-71 pubmed
    ..8), may involve the loss of function of several Hoxd genes. These results indicate the existence of a functional hierarchy among these genes and provide us with an animal model to study human digit malformations. ..
  29. Peichel C, Abbott C, Vogt T. Genetic and physical mapping of the mouse Ulnaless locus. Genetics. 1996;144:1757-67 pubmed
    ..Therefore, the region that must contain the Ulnaless locus has been defined and cloned, which will be invaluable for the identification of the molecular nature of the Ulnaless mutation. ..
  30. Peichel C, Prabhakaran B, Vogt T. The mouse Ulnaless mutation deregulates posterior HoxD gene expression and alters appendicular patterning. Development. 1997;124:3481-92 pubmed
    ..We propose that the Ulnaless mutation alters a cis-acting element that regulates HoxD expression specifically in the appendicular axes of the embryo. ..
  31. Spitz F, Herkenne C, Morris M, Duboule D. Inversion-induced disruption of the Hoxd cluster leads to the partition of regulatory landscapes. Nat Genet. 2005;37:889-93 pubmed
    ..This approach can be used to study the relationship between genome architecture and gene expression, such as the effects of genome rearrangements in human diseases or during evolution. ..
  32. Dolle P, Izpisua Belmonte J, Falkenstein H, Renucci A, Duboule D. Coordinate expression of the murine Hox-5 complex homoeobox-containing genes during limb pattern formation. Nature. 1989;342:767-72 pubmed
  33. Spitz F, Gonzalez F, Peichel C, Vogt T, Duboule D, Zakany J. Large scale transgenic and cluster deletion analysis of the HoxD complex separate an ancestral regulatory module from evolutionary innovations. Genes Dev. 2001;15:2209-14 pubmed
    ..Accordingly, deletion of the entire cluster abolished axial expression, whereas recently acquired regulatory controls were preserved. ..
  34. Tarchini B, Duboule D. Control of Hoxd genes' collinearity during early limb development. Dev Cell. 2006;10:93-103 pubmed
  35. Chiang C, Litingtung Y, Harris M, Simandl B, Li Y, Beachy P, et al. Manifestation of the limb prepattern: limb development in the absence of sonic hedgehog function. Dev Biol. 2001;236:421-35 pubmed
    ..Analysis of GDF5 and Hoxd11-13 expression in the hindlimb autopod suggests that the forming digit has a digit-one identity...
  36. Panman L, Galli A, Lagarde N, Michos O, Soete G, Zuniga A, et al. Differential regulation of gene expression in the digit forming area of the mouse limb bud by SHH and gremlin 1/FGF-mediated epithelial-mesenchymal signalling. Development. 2006;133:3419-28 pubmed
    ..In particular, the expression of Hoxd13 depends on SHH signal transduction significantly longer than does Hoxd11 expression, revealing that the reverse co-linear establishment, but not maintenance of their presumptive digit ..
  37. Nelson L, Rakshit S, Sun H, Wellik D. Generation and expression of a Hoxa11eGFP targeted allele in mice. Dev Dyn. 2008;237:3410-6 pubmed publisher
    ..This targeted mouse line will prove useful as a vital marker for Hoxa11 protein localization during control (heterozygous) or mutant organogenesis. ..
  38. Dolle P, Izpisua Belmonte J, Brown J, Tickle C, Duboule D. HOX-4 genes and the morphogenesis of mammalian genitalia. Genes Dev. 1991;5:1767-7 pubmed
    ..We also show that genital tubercle mesenchyme can respecify pattern in the chicken wing bud. This finding reinforces the concept of the uniformity in the patterning mechanisms along the various axes of the body. ..
  39. Herault Y, Beckers J, Gerard M, Duboule D. Hox gene expression in limbs: colinearity by opposite regulatory controls. Dev Biol. 1999;208:157-65 pubmed
    ..genomic positions within the HoxD cluster such that Hoxd13 and Hoxd12 are necessary for digit development, whereas Hoxd11 and Hoxd10 are involved in making forearms...
  40. Monge I, Kondo T, Duboule D. An enhancer-titration effect induces digit-specific regulatory alleles of the HoxD cluster. Dev Biol. 2003;256:212-20 pubmed
  41. ten Berge D, Brouwer A, Korving J, Martin J, Meijlink F. Prx1 and Prx2 in skeletogenesis: roles in the craniofacial region, inner ear and limbs. Development. 1998;125:3831-42 pubmed
    ..In addition, Prx1 and Prx2 are involved in interactions between perichondrium and chondrocytes that regulate their proliferation or differentiation in the bones of the zeugopods. ..
  42. Zhang Q, Murcia N, Chittenden L, Richards W, Michaud E, Woychik R, et al. Loss of the Tg737 protein results in skeletal patterning defects. Dev Dyn. 2003;227:78-90 pubmed
    ..indicate that the Tg737(orpk) mutant limb defects are not associated with changes in expression of Shh, Ihh, HoxD11-13, Patched, BMPs, or Glis...
  43. Zacchetti G, Duboule D, Zakany J. Hox gene function in vertebrate gut morphogenesis: the case of the caecum. Development. 2007;134:3967-73 pubmed
    ..These results illuminate components of the genetic cascade necessary for the emergence of this gut segment, crucial for many vertebrates. ..
  44. Szumska D, Pieles G, Essalmani R, Bilski M, Mesnard D, Kaur K, et al. VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertase Pcsk5. Genes Dev. 2008;22:1465-77 pubmed publisher
    ..We propose that Pcsk5, at least in part via GDF11, coordinately regulates caudal Hox paralogs, to control anteroposterior patterning, nephrogenesis, skeletal, and anorectal development. ..
  45. Hill P, Götz K, Ruther U. A SHH-independent regulation of Gli3 is a significant determinant of anteroposterior patterning of the limb bud. Dev Biol. 2009;328:506-16 pubmed publisher
    ..Furthermore, we present evidence that the anteroposterior grading of GLI3 activity by the action of SHH is supported by a prototype patterning, which regulates Gli3 independently from SHH. ..
  46. Haramis A, Brown J, Zeller R. The limb deformity mutation disrupts the SHH/FGF-4 feedback loop and regulation of 5' HoxD genes during limb pattern formation. Development. 1995;121:4237-45 pubmed
    ..These studies show that the AER defect in ld homozygous limb buds causes disruption of the FGF-4/SHH feedback loop and support the proposed essential role for FGF-4 in maintaining Shh expression during limb pattern formation. ..
  47. Soshnikova N, Montavon T, Leleu M, Galjart N, Duboule D. Functional analysis of CTCF during mammalian limb development. Dev Cell. 2010;19:819-30 pubmed publisher
    ..We conclude that, at least in this physiological context, rather than being an insulator, CTCF is required for cell survival via the direct transcriptional regulation of target genes critical for cellular homeostasis. ..
  48. Dolle P, Izpisua Belmonte J, Boncinelli E, Duboule D. The Hox-4.8 gene is localized at the 5' extremity of the Hox-4 complex and is expressed in the most posterior parts of the body during development. Mech Dev. 1991;36:3-13 pubmed
    ..8 is expressed in more posterodistal regions than those of its neighbour Hox-4.7. Hence, Hox-4.8 expression appears to be related to the last significant phenotypic changes towards the extremities of the embryonic body and limb axes. ..
  49. Tschopp P, Fraudeau N, Bena F, Duboule D. Reshuffling genomic landscapes to study the regulatory evolution of Hox gene clusters. Proc Natl Acad Sci U S A. 2011;108:10632-7 pubmed publisher
    ..Our results emphasize the importance of evolving regulatory modules rather than their target genes in the process of neo-functionalization and offer a genetic tool to study the complexity of the vertebrate regulatory genome. ..
  50. Yallowitz A, Hrycaj S, Short K, Smyth I, Wellik D. Hox10 genes function in kidney development in the differentiation and integration of the cortical stroma. PLoS ONE. 2011;6:e23410 pubmed publisher
  51. Xu B, Hrycaj S, McIntyre D, Baker N, Takeuchi J, Jeannotte L, et al. Hox5 interacts with Plzf to restrict Shh expression in the developing forelimb. Proc Natl Acad Sci U S A. 2013;110:19438-43 pubmed publisher
    ..These findings, along with previous reports showing that point mutations in the Shh limb enhancer lead to similar anterior limb defects, highlight the importance of Shh repression for proper patterning of the vertebrate limb. ..
  52. Murashima A, Akita H, Okazawa M, Kishigami S, Nakagata N, Nishinakamura R, et al. Midline-derived Shh regulates mesonephric tubule formation through the paraxial mesoderm. Dev Biol. 2014;386:216-26 pubmed publisher
    ..These data demonstrate the essential role of midline-derived Shh in local tissue morphogenesis and differentiation. ..
  53. Booker B, Friedrich T, Mason M, Vandermeer J, Zhao J, Eckalbar W, et al. Bat Accelerated Regions Identify a Bat Forelimb Specific Enhancer in the HoxD Locus. PLoS Genet. 2016;12:e1005738 pubmed publisher
    ..of Hoxd10-Hoxd13 in Miniopterus natalensis bats showed a high-forelimb weak-hindlimb expression for Hoxd10-Hoxd11, similar to the expression trend observed for M...