Gene Symbol: Dll
Description: Distal-less
Alias: Art, BcDNA:LP01770, CG3629, DLL, Dmel\CG3629, E(Arp), En(Arp), dll, l(2)01092, l(2)387, Distal-less, CG3629-PA, CG3629-PB, CG3629-PC, Distall-less, Dll-PA, Dll-PB, Dll-PC, brista, distal-less, distalless, enhancer of Arp
Species: fruit fly
Products:     Dll

Top Publications

  1. Hittinger C, Stern D, Carroll S. Pleiotropic functions of a conserved insect-specific Hox peptide motif. Development. 2005;132:5261-70 pubmed
  2. de Celis Ibeas J, Bray S. Bowl is required downstream of Notch for elaboration of distal limb patterning. Development. 2003;130:5943-52 pubmed
    ..This mechanism might be important in the diversification of arthropod limbs, because it explains how segmented tarsomeres could have arisen from an ancestral limb with an unsegmented tarsus. ..
  3. Zecca M, Basler K, Struhl G. Direct and long-range action of a wingless morphogen gradient. Cell. 1996;87:833-44 pubmed
    ..We interpret these findings as evidence that Wg can act directly and at long range as a gradient morphogen during normal development. ..
  4. Gebelein B, Mckay D, Mann R. Direct integration of Hox and segmentation gene inputs during Drosophila development. Nature. 2004;431:653-9 pubmed
    ..directly with two different segmentation proteins, Sloppy paired and Engrailed, to repress the Hox target gene Distalless in anterior and posterior compartments, respectively...
  5. Giraldez A, Copley R, Cohen S. HSPG modification by the secreted enzyme Notum shapes the Wingless morphogen gradient. Dev Cell. 2002;2:667-76 pubmed
    ..High levels of Wingless signaling induce Notum expression. Thus, Wingless contributes to shaping its own gradient by regulating expression of a protein that modifies its interaction with cell surface proteoglycans. ..
  6. Duncan D, Kiefel P, Duncan I. Control of the spineless antennal enhancer: direct repression of antennal target genes by Antennapedia. Dev Biol. 2010;347:82-91 pubmed publisher
    ..We conclude that the function of Antennapedia in the leg is not to repress homothorax, as has been suggested, but to directly repress spineless and other antennal genes that would otherwise be activated within this ring. ..
  7. Yan D, Wu Y, Feng Y, Lin S, Lin X. The core protein of glypican Dally-like determines its biphasic activity in wingless morphogen signaling. Dev Cell. 2009;17:470-81 pubmed publisher
    ..Based on these data, we propose that the principal function of Dlp is to retain Wg on the cell surface. As such, it can either compete with the receptor or provide ligands to the receptor, depending on the ratios of Wg, Fz2, and Dlp. ..
  8. Calleja M, Moreno E, Pelaz S, Morata G. Visualization of gene expression in living adult Drosophila. Science. 1996;274:252-5 pubmed
    ..The boundary between two of these domains coincides with localized expression of the signaling molecule wingless. ..
  9. Herranz H, Perez L, Martín F, Milan M. A Wingless and Notch double-repression mechanism regulates G1-S transition in the Drosophila wing. EMBO J. 2008;27:1633-45 pubmed publisher
    ..Our results demonstrate that Notch acts in this cellular context as a repressor of cell-cycle progression and Wg has a permissive role in alleviating Notch-mediated repression of G1-S progression in wing cells. ..

More Information


  1. Neumann C, Cohen S. Long-range action of Wingless organizes the dorsal-ventral axis of the Drosophila wing. Development. 1997;124:871-80 pubmed
    ..We propose that Wg acts as a morphogen in patterning the D/V axis of the wing. ..
  2. Zeng Y, Rahnama M, Wang S, Lee W, Verheyen E. Inhibition of Drosophila Wg signaling involves competition between Mad and Armadillo/beta-catenin for dTcf binding. PLoS ONE. 2008;3:e3893 pubmed publisher
  3. Johnston L, Sanders A. Wingless promotes cell survival but constrains growth during Drosophila wing development. Nat Cell Biol. 2003;5:827-33 pubmed
    ..We propose that the cell-survival- and growth-constraining activities of Wg function to sculpt and delimit final wing size as part of its overall patterning programme. ..
  4. Kramps T, Peter O, Brunner E, Nellen D, Froesch B, Chatterjee S, et al. Wnt/wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear beta-catenin-TCF complex. Cell. 2002;109:47-60 pubmed
  5. Estella C, Mckay D, Mann R. Molecular integration of wingless, decapentaplegic, and autoregulatory inputs into Distalless during Drosophila leg development. Dev Cell. 2008;14:86-96 pubmed publisher
    ..and Wingless (Wg), two signals that establish the proximo-distal (PD) axis by activating target genes such as Distalless (Dll)...
  6. Sato A, Kojima T, Ui Tei K, Miyata Y, Saigo K. Dfrizzled-3, a new Drosophila Wnt receptor, acting as an attenuator of Wingless signaling in wingless hypomorphic mutants. Development. 1999;126:4421-30 pubmed
    ..Wingless signaling may thus be attenuated by Dfrizzled-3 at least in wingless hypomorphic mutants. ..
  7. Duncan D, Burgess E, Duncan I. Control of distal antennal identity and tarsal development in Drosophila by spineless-aristapedia, a homolog of the mammalian dioxin receptor. Genes Dev. 1998;12:1290-303 pubmed
    ..In both the antenna and leg, ss expression is shown to depend on Distal-less (Dll), a master regulator of ventral appendage formation...
  8. Kojima T, Sato M, Saigo K. Formation and specification of distal leg segments in Drosophila by dual Bar homeobox genes, BarH1 and BarH2. Development. 2000;127:769-78 pubmed
    ..Bar homeobox genes are also required for specification of distal tarsi. Bar expression requires Distal-less but not dachshund, while early circular dachshund expression is delimited interiorly by BarH1 and BarH2. ..
  9. Agelopoulos M, Mckay D, Mann R. Developmental regulation of chromatin conformation by Hox proteins in Drosophila. Cell Rep. 2012;1:350-9 pubmed
    ..We applied this approach to Distalless (Dll), a gene required for limb development in Drosophila...
  10. Merabet S, Litim Mecheri I, Karlsson D, Dixit R, Saadaoui M, Monier B, et al. Insights into Hox protein function from a large scale combinatorial analysis of protein domains. PLoS Genet. 2011;7:e1002302 pubmed publisher
  11. Franch Marro X, Marchand O, Piddini E, Ricardo S, Alexandre C, Vincent J. Glypicans shunt the Wingless signal between local signalling and further transport. Development. 2005;132:659-66 pubmed
    ..signalling is increased at the expense of long-range signalling (reported by the expression of the target gene distalless) while the reverse is caused by Dally-like overexpression...
  12. Panàkovà D, Sprong H, Marois E, Thiele C, Eaton S. Lipoprotein particles are required for Hedgehog and Wingless signalling. Nature. 2005;435:58-65 pubmed
    ..Similarly, the range of Wingless signalling is narrowed. We propose a novel function for lipoprotein particles, in which they act as vehicles for the movement of lipid-linked morphogens and glycophosphatidylinositol-linked proteins. ..
  13. Cohen B, Simcox A, Cohen S. Allocation of the thoracic imaginal primordia in the Drosophila embryo. Development. 1993;117:597-608 pubmed
    ..We have used a molecular probe derived from the Distal-less (Dll) gene to show that this population contains progenitor cells for both the dorsal (i.e. wing) and ventral (i.e...
  14. Kreuger J, Perez L, Giraldez A, Cohen S. Opposing activities of Dally-like glypican at high and low levels of Wingless morphogen activity. Dev Cell. 2004;7:503-12 pubmed
    ..Notum-induced shedding of Dlp could convert Dlp from a membrane-tethered coreceptor to a secreted antagonist. ..
  15. Kubota K, Goto S, Eto K, Hayashi S. EGF receptor attenuates Dpp signaling and helps to distinguish the wing and leg cell fates in Drosophila. Development. 2000;127:3769-76 pubmed
    ..and leg precursors of Drosophila are recruited from a common pool of ectodermal cells expressing the homeobox gene Dll. Induction by Dpp promotes this cell fate decision toward the wing and proximal leg...
  16. Shu J, Li Y. A statistical fat-tail test of predicting regulatory regions in the Drosophila genome. Comput Biol Med. 2012;42:935-41 pubmed publisher
    ..These two fatness coefficients may serve as valuable filtering indexes to predict CRMs experimentally. ..
  17. Cummins M, Pueyo J, Greig S, Couso J. Comparative analysis of leg and antenna development in wild-type and homeotic Drosophila melanogaster. Dev Genes Evol. 2003;213:319-27 pubmed
    ..The partial conservation of pattern-forming genes in both appendages ensures a predictable re-specification of positional clues, producing the observed positional specificity of homeotic transformations. ..
  18. Mckay D, Estella C, Mann R. The origins of the Drosophila leg revealed by the cis-regulatory architecture of the Distalless gene. Development. 2009;136:61-71 pubmed publisher
    ..into these two domains occurs during embryogenesis and is reflected in the cis-regulatory architecture of the Distalless (Dll) gene...
  19. Wu J, Cohen S. Proximodistal axis formation in the Drosophila leg: subdivision into proximal and distal domains by Homothorax and Distal-less. Development. 1999;126:109-17 pubmed
    ..into proximal and distal domains by the activity of the homeodomain proteins Homothorax (Hth) and Distal-less (Dll). The expression domains of Dll and Hth are initially reciprocal...
  20. Estella C, Rieckhof G, Calleja M, Morata G. The role of buttonhead and Sp1 in the development of the ventral imaginal discs of Drosophila. Development. 2003;130:5929-41 pubmed
    ..They act as activators of the headcase (hdc) and Distal-less (Dll) genes, which allocate the cells of the disc primordia...
  21. Giorgianni M, Mann R. Establishment of medial fates along the proximodistal axis of the Drosophila leg through direct activation of dachshund by Distalless. Dev Cell. 2011;20:455-68 pubmed publisher
    ..According to this model, high [Wg+Dpp] activates Distalless (Dll) and represses dachshund (dac) in the distal cells of the leg disc, while intermediate [Wg+Dpp] activates ..
  22. Giraldez A, Cohen S. Wingless and Notch signaling provide cell survival cues and control cell proliferation during wing development. Development. 2003;130:6533-43 pubmed
    ..However, only part of this effect was attributable to Notch-dependent induction of Wg, suggesting that other Notch-inducible signaling molecules contribute to the control of cell proliferation in the wing. ..
  23. Panganiban G, Nagy L, Carroll S. The role of the Distal-less gene in the development and evolution of insect limbs. Curr Biol. 1994;4:671-5 pubmed
    ..studies of the expression and regulation during development of limb-patterning genes, such as Distal-less (Dll), may provide insights into arthropod evolution...
  24. Galant R, Walsh C, Carroll S. Hox repression of a target gene: extradenticle-independent, additive action through multiple monomer binding sites. Development. 2002;129:3115-26 pubmed
  25. Gebelein B, Culi J, Ryoo H, Zhang W, Mann R. Specificity of Distalless repression and limb primordia development by abdominal Hox proteins. Dev Cell. 2002;3:487-98 pubmed
    ..The Hox protein Ultrabithorax (Ubx) suppresses limb formation in the abdomen by repressing the leg selector gene Distalless, whereas Antennapedia (Antp), a thoracic Hox protein, does not repress Distalless...
  26. Galindo M, Couso J. Intercalation of cell fates during tarsal development in Drosophila. Bioessays. 2000;22:777-80 pubmed
  27. Lecuit T, Cohen S. Proximal-distal axis formation in the Drosophila leg. Nature. 1997;388:139-45 pubmed
    ..Subsequent modulation of the relative sizes of these domains by growth of the leg is required to form the mature pattern. ..
  28. Lin X, Perrimon N. Dally cooperates with Drosophila Frizzled 2 to transduce Wingless signalling. Nature. 1999;400:281-4 pubmed
    ..Our results indicate that Dally may act as a co-receptor for Wg, and that Dally, together with Drosophila Frizzled 2, modulates both short- and long-range activities of Wg. ..
  29. Cohen S, Bronner G, Küttner F, Jurgens G, Jackle H. Distal-less encodes a homoeodomain protein required for limb development in Drosophila. Nature. 1989;338:432-4 pubmed
    ..The molecular structure of the Distal-less locus indicates that the gene encodes a homoeodomain-containing protein which is therefore likely to specify limb development through differential regulation of subordinate genes. ..
  30. Panganiban G, Sebring A, Nagy L, Carroll S. The development of crustacean limbs and the evolution of arthropods. Science. 1995;270:1363-6 pubmed
    ..the use of molecular probes, including an antibody to proteins encoded by arthropod and vertebrate Distal-less (Dll and Dlx) genes, provided evidence that common genetic mechanisms underlie the development of all arthropod limbs ..
  31. Panganiban G, Rubenstein J. Developmental functions of the Distal-less/Dlx homeobox genes. Development. 2002;129:4371-86 pubmed
    ..We review what is known about the invertebrate and vertebrate Dll/Dlx genes and their varied roles during development...
  32. Merabet S, Saadaoui M, Sambrani N, Hudry B, Pradel J, Affolter M, et al. A unique Extradenticle recruitment mode in the Drosophila Hox protein Ultrabithorax. Proc Natl Acad Sci U S A. 2007;104:16946-51 pubmed
  33. Pueyo J, Couso J. The 11-aminoacid long Tarsal-less peptides trigger a cell signal in Drosophila leg development. Dev Biol. 2008;324:192-201 pubmed publisher
    ..These regulatory effects complement the known genetic scenario required for distal leg development and explain the requirements for tarsal-less in this process. ..
  34. Baena Lopez L, Garcia Bellido A. Control of growth and positional information by the graded vestigial expression pattern in the wing of Drosophila melanogaster. Proc Natl Acad Sci U S A. 2006;103:13734-9 pubmed
    ..Our observations provide evidence that local cell interactions, triggered by differences in vestigial expression between neighboring cells, confer positional values operating in the control of growth and shape of the wing. ..
  35. Galindo M, Bishop S, Greig S, Couso J. Leg patterning driven by proximal-distal interactions and EGFR signaling. Science. 2002;297:256-9 pubmed
    ..signaling establishes the proximal-distal axis of Drosophila legs by activating the expression of genes such as Distalless and dachshund in broad proximal-distal domains during early leg development...
  36. Gorfinkiel N, Morata G, Guerrero I. The homeobox gene Distal-less induces ventral appendage development in Drosophila. Genes Dev. 1997;11:2259-71 pubmed
    This study investigates the role of the homeobox gene Distal-less (Dll) in the development of the legs, antennae, and wings of Drosophila...
  37. Merabet S, Kambris Z, Capovilla M, Bérenger H, Pradel J, Graba Y. The hexapeptide and linker regions of the AbdA Hox protein regulate its activating and repressive functions. Dev Cell. 2003;4:761-8 pubmed
    ..Our in vivo data thus reveal functions not previously anticipated from in vitro analyses for the hexapeptide motif in the regulation of Hox activity. ..
  38. Hamada F, Tomoyasu Y, Takatsu Y, Nakamura M, Nagai S, Suzuki A, et al. Negative regulation of Wingless signaling by D-axin, a Drosophila homolog of axin. Science. 1999;283:1739-42 pubmed
    ..Hence, D-Axin negatively regulates Wingless signaling by down-regulating the level of Armadillo. These results establish the importance of the Axin family of proteins in Wnt/Wingless signaling in Drosophila. ..
  39. Piddini E, Marshall F, Dubois L, Hirst E, Vincent J. Arrow (LRP6) and Frizzled2 cooperate to degrade Wingless in Drosophila imaginal discs. Development. 2005;132:5479-89 pubmed
    ..Overall, Frizzled2 achieves ligand capture and internalization, whereas Arrow, and perhaps downstream signalling, are essential for lysosomal targeting. ..
  40. Cohen S. Specification of limb development in the Drosophila embryo by positional cues from segmentation genes. Nature. 1990;343:173-7 pubmed
    ..This analysis allows a direct molecular visualization of the compartments that subdivide the limb primordia into discrete developmental domains. ..
  41. Diaz Benjumea F, Cohen S. Serrate signals through Notch to establish a Wingless-dependent organizer at the dorsal/ventral compartment boundary of the Drosophila wing. Development. 1995;121:4215-25 pubmed
    ..Ligand independent activation of Notch is sufficient to direct Wg expression, which in turn mediates the organizing activity of the D/V boundary. ..
  42. Tour E, Hittinger C, McGinnis W. Evolutionarily conserved domains required for activation and repression functions of the Drosophila Hox protein Ultrabithorax. Development. 2005;132:5271-81 pubmed
    ..These results suggest that the N-terminal region containing the SSYF motif has been conserved in many Hox proteins for its role in transcriptional activation. ..
  43. Dong P, Chu J, Panganiban G. Coexpression of the homeobox genes Distal-less and homothorax determines Drosophila antennal identity. Development. 2000;127:209-16 pubmed
    ..Based on their genetic and biochemical properties, we propose that Homothorax and Extradenticle may serve as antenna-specific cofactors for Distal-less. ..
  44. Abu Shaar M, Mann R. Generation of multiple antagonistic domains along the proximodistal axis during Drosophila leg development. Development. 1998;125:3821-30 pubmed
    ..We demonstrate that WG and DPP act together through their targets Distal-less (Dll) and dachshund (dac) to restrict hth expression, and therefore EXD's nuclear localization, to the most proximal ..
  45. Estrada B, Sánchez Herrero E. The Hox gene Abdominal-B antagonizes appendage development in the genital disc of Drosophila. Development. 2001;128:331-9 pubmed
    ..We propose that the genital primordia should be subdivided into two regions, one of them competent to be transformed into an appendage in the absence of Abdominal-B. ..
  46. Morata G, Sánchez Herrero E. Patterning mechanisms in the body trunk and the appendages of Drosophila. Development. 1999;126:2823-8 pubmed
    ..We speculate that, although the basic mechanisms are similar, there are significant differences in the manner the body trunk and appendages respond to them. ..
  47. Estella C, Mann R. Logic of Wg and Dpp induction of distal and medial fates in the Drosophila leg. Development. 2008;135:627-36 pubmed publisher
    ..Wg and Dpp are also required to pattern the dorsoventral (DV) axis of the leg. Here, we show that Distalless (Dll) and dachshund (dac), genes expressed at different positions along the PD axis, are activated by Wg ..
  48. Parker D, Jemison J, Cadigan K. Pygopus, a nuclear PHD-finger protein required for Wingless signaling in Drosophila. Development. 2002;129:2565-76 pubmed
    ..Our data argue strongly that Pygopus is a new core component of the Wg signaling pathway that acts downstream or at the level of TCF. ..
  49. McGinnis W, Krumlauf R. Homeobox genes and axial patterning. Cell. 1992;68:283-302 pubmed
  50. Casares F, Mann R. A dual role for homothorax in inhibiting wing blade development and specifying proximal wing identities in Drosophila. Development. 2000;127:1499-508 pubmed
    ..Our results suggest that tsh and hth block wing blade development by repressing some of the activities of the Notch pathway at the D/V compartment boundary. ..
  51. Seto E, Bellen H. Internalization is required for proper Wingless signaling in Drosophila melanogaster. J Cell Biol. 2006;173:95-106 pubmed
    ..As these data indicate that endosomal transport promotes Wg signaling, our findings suggest that the regulation of endocytosis is a novel mechanism through which Wg signaling levels are determined. ..
  52. Lelli K, Noro B, Mann R. Variable motif utilization in homeotic selector (Hox)-cofactor complex formation controls specificity. Proc Natl Acad Sci U S A. 2011;108:21122-7 pubmed publisher
    ..We propose that using different binding mechanisms with the same cofactor may be one strategy to achieve functional specificity in vivo. ..
  53. Ronshaugen M, McGinnis N, McGinnis W. Hox protein mutation and macroevolution of the insect body plan. Nature. 2002;415:914-7 pubmed
    ..Here we show that naturally selected alteration of the Ubx protein is linked to the evolutionary transition to hexapod limb pattern. ..
  54. Cohen S, Jurgens G. Mediation of Drosophila head development by gap-like segmentation genes. Nature. 1990;346:482-5 pubmed
    ..We report here that three previously identified zygotic genes buttonhead (btd), empty spiracles (ems) and orthodenticle (otd) may behave like gap genes that mediate bcd function in the embryonic head. ..
  55. Culi J, Mann R. Boca, an endoplasmic reticulum protein required for wingless signaling and trafficking of LDL receptor family members in Drosophila. Cell. 2003;112:343-54 pubmed
    ..Consequently, boca is an essential component of the Wingless pathway but is more generally required for the activities of multiple LDL receptor family members. ..
  56. Takei Y, Ozawa Y, Sato M, Watanabe A, Tabata T. Three Drosophila EXT genes shape morphogen gradients through synthesis of heparan sulfate proteoglycans. Development. 2004;131:73-82 pubmed
    ..We propose that HSPGs facilitate the spreading of morphogens and therefore, function to generate morphogen concentration gradients. ..
  57. Campbell G, Tomlinson A. The roles of the homeobox genes aristaless and Distal-less in patterning the legs and wings of Drosophila. Development. 1998;125:4483-93 pubmed
    ..wing imaginal discs of Drosophila, the expression domains of the homeobox genes aristaless (al) and Distal-less (Dll) are defined by the secreted signaling molecules Wingless (Wg) and Decapentaplegic (Dpp)...
  58. Lebreton G, Faucher C, Cribbs D, Benassayag C. Timing of Wingless signalling distinguishes maxillary and antennal identities in Drosophila melanogaster. Development. 2008;135:2301-9 pubmed publisher
    ..We characterised: (1) the action of Wg through ss selector function in distinguishing maxillary from antenna; and (2) its direct contribution to identity choice. ..
  59. Chu J, Dong P, Panganiban G. Limb type-specific regulation of bric a brac contributes to morphological diversity. Development. 2002;129:695-704 pubmed
    ..We propose that the limb type-specific variations in expression of bric a brac repressors contribute to morphological variations by controlling distal limb segment number. ..
  60. Diaz Benjumea F, Cohen B, Cohen S. Cell interaction between compartments establishes the proximal-distal axis of Drosophila legs. Nature. 1994;372:175-9 pubmed
    ..These results demonstrate that sequential interaction between anterior-posterior and dorsal-ventral compartments establishes the proximal-distal axis of the limbs. ..
  61. Han C, Belenkaya T, Khodoun M, Tauchi M, Lin X, Lin X. Distinct and collaborative roles of Drosophila EXT family proteins in morphogen signalling and gradient formation. Development. 2004;131:1563-75 pubmed
    ..Our results also suggest that HSPGs have two distinct roles in Wg morphogen distribution and signalling...
  62. Bolinger R, Boekhoff Falk G. Distal-less functions in subdividing the Drosophila thoracic limb primordium. Dev Dyn. 2005;232:801-16 pubmed
  63. Couso J, Bishop S. Proximo-distal development in the legs of Drosophila. Int J Dev Biol. 1998;42:345-52 pubmed
    ..The data suggest a process of regionalization and progressive subdivision of an anlage similar to both insect embryonic segmentation and vertebrate somitogenesis. ..
  64. Cadigan K, Fish M, Rulifson E, Nusse R. Wingless repression of Drosophila frizzled 2 expression shapes the Wingless morphogen gradient in the wing. Cell. 1998;93:767-77 pubmed
    ..In contrast to other ligand-receptor relationships where the receptor limits diffusion of the ligand, Dfz2 broadens the range of Wg action by protecting it from degradation. ..
  65. Marquez R, Singer M, Takaesu N, Waldrip W, Kraytsberg Y, Newfeld S. Transgenic analysis of the Smad family of TGF-beta signal transducers in Drosophila melanogaster suggests new roles and new interactions between family members. Genetics. 2001;157:1639-48 pubmed
    ..Overall, the study demonstrates that transgenic methods in Drosophila can provide new information about non-Drosophila members of developmentally important multigene families. ..
  66. Campbell G. Distalization of the Drosophila leg by graded EGF-receptor activity. Nature. 2002;418:781-5 pubmed
    ..This similarity between proximodistal patterning in vertebrates and flies supports previous suggestions of an evolutionary relationship between appendages/body-wall outgrowths in animals. ..
  67. Vachon G, Cohen B, Pfeifle C, McGuffin M, Botas J, Cohen S. Homeotic genes of the Bithorax complex repress limb development in the abdomen of the Drosophila embryo through the target gene Distal-less. Cell. 1992;71:437-50 pubmed
    ..Repression of limb development in the abdomen appears to be controlled at the DII enhancer. Thus DII may serve as a downstream target gene through which the homeotic genes control abdominal segment identity in the Drosophila embryo. ..