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Gene Review

Dll  -  Distal-less

Drosophila melanogaster

Synonyms: 2.7, Art, BR, Ba, BcDNA:LP01770, ...
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Disease relevance of Dll

  • We show that this gene encodes a 2.7 kb mRNA which is expressed during mouse embryogenesis and during differentiation of F9 teratocarcinoma cells into parietal endoderm cells [1].
  • At a flight force that exactly compensates body weight, the temporal deviations with which fruit flies vary their stroke amplitude and frequency are approximately 2.7 degrees and 4.8 Hz of their mean value, respectively [2].

High impact information on Dll

  • Homeotic genes of the Bithorax complex repress limb development in the abdomen of the Drosophila embryo through the target gene Distal-less [3].
  • Localized expression of the homeobox gene Distal-less (DII) is required for leg development in thoracic segments [3].
  • We have determined the 2.7 A resolution crystal structure of the alpha 2 homeodomain bound to a biologically relevant DNA sequence [4].
  • Synthesis of a 2.7 kb poly(A)+ transcript of the engrailed region was found in precellular embryos [5].
  • This cluster is separated from other tRNA regions on the chromosome by at least 2.7 kb on one side, and 9.6 kb on the other [6].

Biological context of Dll

  • The roles of the homeobox genes aristaless and Distal-less in patterning the legs and wings of Drosophila [7].
  • Dll has a crucial role in Drosophila limb morphogenesis, partially specifying pattern along the proximo-distal axis of the limb [8].
  • Although we show that Dll function is not required for allocation of imaginal cells, activation of an early Dll enhancer may serve as a molecular marker for allocation [9].
  • However, unlike other homeotic genes, Dll expression and function is not defined by a cell lineage border [10].
  • We examined gene expression patterns in three orders of hexapods, all of which develop abdominal appendages, in order to determine when the strong repressive interaction between BX-C proteins and Dll appeared during evolution [11].

Anatomical context of Dll

  • Dll protein can be detected in a central domain in leg discs throughout most of larval development, and in mature discs this domain corresponds to the distal-most region of the leg, the tarsus and the distal tibia [7].
  • 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. leg) discs [9].
  • A mouse gene related to Distal-less shows a restricted expression in the developing forebrain [8].
  • We postulate that this may reflect a pleisiomorphic function of Dll in development of the peripheral nervous system [12].
  • Homeobox genes of the Distal-less (Dll) class are expressed in developing appendages as well as in the central nervous system in invertebrates and vertebrates [13].

Associations of Dll with chemical compounds

  • Polyadenylic acid-containing transcripts of 2.7, 2.2, and 1.7 kilobases (kb) in embryos, pupae, adults, and Kc cells and an additional 1.4-kb transcript in adults were complementary to the Drosophila genomic clones and to v-myc [14].
  • 10 g of polypeptide has attached 6.4 g of glucosamine, 3.1 g of galactosamine, 6.1 g of uronic acid, and 2.7 g of neutral sugars [15].
  • The reversible urea unfolding of either isolated apo-domain follows a two-state mechanism with relatively low deltaG(o)20 values of approximately 2.7 (N-domain) and approximately 1.9 kcal/mol (C-domain) [16].
  • The ratio for 1,2-dibromoethane, 2.7, indicates that it may act as a monofunctional agent [17].
  • The ratio of the slopes of these two response curves is 2.7 +/- 0.3, yielding a relative biological effectiveness that suggests the tritium beta particle is 2.7 times more effective per unit of energy absorbed in inducing gene mutations transmitted to successive generations than 60Co gamma radiation [18].

Physical interactions of Dll

  • This suggests that Ubx cooperatively assembles a multi-protein repression complex on Distal-less regulatory DNA with the YPWM motif as a key protein-protein interface in this complex [19].
  • Biochemical analyses revealed the N-terminal (30aa to 124aa) and C-terminal (190aa to 327aa) regions of Dll to interact with the DNA binding domain (16aa to 125aa) of dDREF, although it is not clear yet whether the interaction is direct or indirect [20].

Regulatory relationships of Dll

  • However, if en is expressed uniformly via a heat-shock promoter, Ubx is repressed and Dll is derepressed [21].
  • Wg and Dpp do not act through Dll to repress Hth [22].
  • In addition, we show that dac negatively regulates Dll [23].
  • Meanwhile targeted ectopic Dll represses eve expression and hindgut formation [24].
  • Here we show that the combined action of wg-expressing cells in the ventral-anterior compartment and dpp-expressing cells in the dorsal-anterior compartment activates expression of Distal-less, a gene required for proximal-distal axis formation in the limbs [25].

Other interactions of Dll

  • If Ubx is expressed uniformly via a heat-shock promoter, Dll is inappropriately repressed in these posterior compartment cells [21].
  • The expression domains of Dll and Hth are initially reciprocal [22].
  • Here, the roles played by al and Dll in patterning the legs and wings have been investigated through loss of function studies [7].
  • Different expression dynamics of dachshund and Distal-less point to modifications in the regulation of the leg gap gene system [26].
  • The lack of Dll function in the anal primordia transforms the anal tissue into hindgut by the extension of the eve domain [24].

Analytical, diagnostic and therapeutic context of Dll

  • X-dll3 differs from the other Xenopus genes and the previously isolated Dll-related mouse genes, in that localized expression can be detected by in situ hybridization very early in development, in the anterior-transverse ridge of the open neural plate [27].
  • Electrophoretic mobility shift assays showed that Dll thereby inhibits DNA binding [20].
  • Northern blot analyses revealed four FLAP messages of approximately 2.7, 2.9, 3.3, and 5.1 kb, which are differentially expressed in the tissues tested [28].
  • Using polymerase chain reaction technology, we have identified four murine homologs of the Drosophila Distal-less homeobox gene that are expressed in midgestation embryos [29].


  1. Sequential expression of murine homeo box genes during F9 EC cell differentiation. Breier, G., Bućan, M., Francke, U., Colberg-Poley, A.M., Gruss, P. EMBO J. (1986) [Pubmed]
  2. The production of elevated flight force compromises manoeuvrability in the fruit fly Drosophila melanogaster. Lehmann, F.O., Dickinson, M.H. J. Exp. Biol. (2001) [Pubmed]
  3. Homeotic genes of the Bithorax complex repress limb development in the abdomen of the Drosophila embryo through the target gene Distal-less. Vachon, G., Cohen, B., Pfeifle, C., McGuffin, M.E., Botas, J., Cohen, S.M. Cell (1992) [Pubmed]
  4. Crystal structure of a MAT alpha 2 homeodomain-operator complex suggests a general model for homeodomain-DNA interactions. Wolberger, C., Vershon, A.K., Liu, B., Johnson, A.D., Pabo, C.O. Cell (1991) [Pubmed]
  5. The engrailed locus of D. melanogaster provides an essential zygotic function in precellular embryos. Karr, T.L., Ali, Z., Drees, B., Kornberg, T. Cell (1985) [Pubmed]
  6. Analysis of a drosophila tRNA gene cluster: two tRNALeu genes contain intervening sequences. Robinson, R.R., Davidson, N. Cell (1981) [Pubmed]
  7. The roles of the homeobox genes aristaless and Distal-less in patterning the legs and wings of Drosophila. Campbell, G., Tomlinson, A. Development (1998) [Pubmed]
  8. A mouse gene related to Distal-less shows a restricted expression in the developing forebrain. Price, M., Lemaistre, M., Pischetola, M., Di Lauro, R., Duboule, D. Nature (1991) [Pubmed]
  9. Allocation of the thoracic imaginal primordia in the Drosophila embryo. Cohen, B., Simcox, A.A., Cohen, S.M. Development (1993) [Pubmed]
  10. The homeobox gene Distal-less induces ventral appendage development in Drosophila. Gorfinkiel, N., Morata, G., Guerrero, I. Genes Dev. (1997) [Pubmed]
  11. Evolution of the interaction between Hox genes and a downstream target. Palopoli, M.F., Patel, N.H. Curr. Biol. (1998) [Pubmed]
  12. A complex role for distal-less in crustacean appendage development. Williams, T.A., Nulsen, C., Nagy, L.M. Dev. Biol. (2002) [Pubmed]
  13. The Caenorhabditis elegans distal-less ortholog ceh-43 is required for development of the anterior hypodermis. Aspöck, G., Bürglin, T.R. Dev. Dyn. (2001) [Pubmed]
  14. Family of developmentally regulated, maternally expressed Drosophila RNA species detected by a v-myc probe. Madhavan, K., Bilodeau-Wentworth, D., Wadsworth, S.C. Mol. Cell. Biol. (1985) [Pubmed]
  15. Papilin: a Drosophila proteoglycan-like sulfated glycoprotein from basement membranes. Campbell, A.G., Fessler, L.I., Salo, T., Fessler, J.H. J. Biol. Chem. (1987) [Pubmed]
  16. Ligand binding and thermodynamic stability of a multidomain protein, calmodulin. Masino, L., Martin, S.R., Bayley, P.M. Protein Sci. (2000) [Pubmed]
  17. The ratio of induced recessive lethals to ring-X loss has prognostic value in terms of functionality of chemical mutagens in Drosophila melanogaster. Zijlstra, J.A., Vogel, E.W. Mutat. Res. (1988) [Pubmed]
  18. Relative biological effectiveness of tritiated water to gamma radiation for germ line mutations. Byrne, B.J., Lee, W.R. Radiat. Res. (1989) [Pubmed]
  19. Evolutionarily conserved domains required for activation and repression functions of the Drosophila Hox protein Ultrabithorax. Tour, E., Hittinger, C.T., McGinnis, W. Development (2005) [Pubmed]
  20. Drosophila distal-less negatively regulates dDREF by inhibiting its DNA binding activity. Hayashi, Y., Kato, M., Seto, H., Yamaguchi, M. Biochim. Biophys. Acta (2006) [Pubmed]
  21. Engrailed-mediated repression of Ultrabithorax is necessary for the parasegment 6 identity in Drosophila. Mann, R.S. Development (1994) [Pubmed]
  22. Proximodistal axis formation in the Drosophila leg: subdivision into proximal and distal domains by Homothorax and Distal-less. Wu, J., Cohen, S.M. Development (1999) [Pubmed]
  23. Generation of multiple antagonistic domains along the proximodistal axis during Drosophila leg development. Abu-Shaar, M., Mann, R.S. Development (1998) [Pubmed]
  24. Drosophila terminalia as an appendage-like structure. Gorfinkiel, N., Sánchez, L., Guerrero, I. Mech. Dev. (1999) [Pubmed]
  25. Cell interaction between compartments establishes the proximal-distal axis of Drosophila legs. Diaz-Benjumea, F.J., Cohen, B., Cohen, S.M. Nature (1994) [Pubmed]
  26. Gene expression in spider appendages reveals reversal of exd/hth spatial specificity, altered leg gap gene dynamics, and suggests divergent distal morphogen signaling. Prpic, N.M., Janssen, R., Wigand, B., Klingler, M., Damen, W.G. Dev. Biol. (2003) [Pubmed]
  27. Xenopus Distal-less related homeobox genes are expressed in the developing forebrain and are induced by planar signals. Papalopulu, N., Kintner, C. Development (1993) [Pubmed]
  28. Identification of the binding partners for flightless I, A novel protein bridging the leucine-rich repeat and the gelsolin superfamilies. Liu, Y.T., Yin, H.L. J. Biol. Chem. (1998) [Pubmed]
  29. Spatially restricted expression of a member of a new family of murine Distal-less homeobox genes in the developing forebrain. Robinson, G.W., Wray, S., Mahon, K.A. New Biol. (1991) [Pubmed]
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