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Gene Review

Dfd  -  Deformed

Drosophila melanogaster

Synonyms: BG:DS00276.5, CG2189, DmDfd, Dmel\CG2189, EbR11, ...
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Disease relevance of Dfd

  • In a search through 35 kb of Dfd sequences for additional transcriptional control elements, we have identified a 3.2 kb DNA fragment containing an enhancer that mimics the expression of Dfd in the subesophageal ganglion of the embryonic central nervous system [1].

High impact information on Dfd

  • Dfd accomplishes this by directly activating the cell death promoting gene reaper (rpr) [2].
  • We show that during early Drosophila development, the Hox protein Deformed (Dfd) maintains the boundary between the maxillary and mandibular head lobes by activating localized apoptosis [2].
  • To test the role of the homeodomain in determining target specificity, we replaced the homeobox of Deformed with the homeobox of Ultrabithorax [3].
  • With these strains we can induce the ectopic expression of Dfd protein in other segments at various stages of embryonic development [4].
  • This possibility is supported by the finding that a Drosophila Dfd autoregulatory element supplies spatially localized expression in the hindbrain of mouse embryos [5].

Biological context of Dfd

  • One of the ancestral homeobox genes that arose close to the root of the Eumetazoa appears to have given rise to Dfd, Scr, and the Antennapedia homeobox-class homeotic genes [6].
  • With regard to imaginal development, lab and Dfd occupy adjacent non-overlapping expression domains in the peripodial cell layer of the eye-antennal disc, in patterns that are consistent with their adult mutant phenotypes and published fate maps [7].
  • During embryogenesis, lab and Dfd exhibit limited overlapping expression in areas that are of no obvious significance to the development of larval head structures, but also in areas that may have consequences for imaginal development [7].
  • Finally, deletion of potential cofactor binding sites flanking the HB1 element that are also conserved in the medaka, chicken, and mouse genes revealed that they are important for enhancer function in Drosophila and that the Dfd-dependent and the Ubx-dependent expression requires different sites [8].
  • Mutations in lab, like those in the Deformed and proboscipedia loci of the ANT-C, reveal a homoeotic phenotype only in the adult stage of the life cycle [9].

Anatomical context of Dfd

  • Tc Deformed (Tc Dfd) is expressed in the blastoderm and the condensing germ rudiment in a region that gives rise to gnathal segments [10].
  • When Tc Dfd is expressed throughout embryonic ectoderm under the control of P69B, the beetle protein autoregulates the endogenous Dfd gene [10].
  • Lox6, a leech Dfd ortholog, is expressed in the central nervous system and in peripheral sensory structures [11].

Associations of Dfd with chemical compounds

  • Although the position of the chimera relative to DNA, as judged by hydroxyl radical footprinting, is similar to that of the Dfd HD, the missing nucleoside and methylation interference patterns resemble those of the Ubx HD [12].

Physical interactions of Dfd


Regulatory relationships of Dfd

  • Mutant analyses demonstrate that Scr and Dfd regulate pb in their normal domains of expression during embryogenesis [16].
  • The good correlation between the in vitro DNA binding preferences of these four Antp-type homeodomain proteins and their ability to specifically regulate a Dfd enhancer element in the embryo, suggests that the modest binding differences that distinguish them make an important contribution to their unique regulatory specificities [17].
  • In the head, Deformed is required to activate Serrate transcription in the maxillary segment, where Serrate is required for normal mouth hook morphogenesis [18].
  • The basic-leucine zipper protein Cap 'n' collar B (CncB) suppresses the segmental identity function of the Hox gene Deformed (Dfd) in the mandibular segment of Drosophila embryos [19].

Other interactions of Dfd

  • The gnathal segments of Dfd and Scr mutant larvae are abnormal but not homeotically transformed [6].
  • Given this unique ontogenetic and phylogenetic history and the observation that homeotic transformations produced by the lab, Dfd, and proboscipedia (pb) loci are manifested only in the adult, we suggest that distinct regulatory paradigms evolved for homeotic gene function in the development of the larval versus adult head [7].
  • The wg product, in addition to that of Dfd, appears to be sufficient to activate the endogenous Dfd gene in many embryonic cells [20].
  • Second, the orientation of the Deformed gene is inverted in D. pseudoobscura, providing it with a 5' to 3' direction of transcription identical to the remaining ANT-C homeobox genes with the exception of fushi tarazu [21].
  • Prior developmental genetic analyses have shown that labial (lab) and Deformed (Dfd) are homeotic genes that function in the development of the embryonic (larval) and adult head [7].

Analytical, diagnostic and therapeutic context of Dfd


  1. Deformed expression in the Drosophila central nervous system is controlled by an autoactivated intronic enhancer. Lou, L., Bergson, C., McGinnis, W. Nucleic Acids Res. (1995) [Pubmed]
  2. The Drosophila Hox gene deformed sculpts head morphology via direct regulation of the apoptosis activator reaper. Lohmann, I., McGinnis, N., Bodmer, M., McGinnis, W. Cell (2002) [Pubmed]
  3. A homeodomain substitution changes the regulatory specificity of the deformed protein in Drosophila embryos. Kuziora, M.A., McGinnis, W. Cell (1989) [Pubmed]
  4. Autoregulation of a Drosophila homeotic selector gene. Kuziora, M.A., McGinnis, W. Cell (1988) [Pubmed]
  5. A human HOX4B regulatory element provides head-specific expression in Drosophila embryos. Malicki, J., Cianetti, L.C., Peschle, C., McGinnis, W. Nature (1992) [Pubmed]
  6. Implications of the Tribolium Deformed mutant phenotype for the evolution of Hox gene function. Brown, S., DeCamillis, M., Gonzalez-Charneco, K., Denell, M., Beeman, R., Nie, W., Denell, R. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  7. Developmental and evolutionary implications of labial, Deformed and engrailed expression in the Drosophila head. Diederich, R.J., Pattatucci, A.M., Kaufman, T.C. Development (1991) [Pubmed]
  8. A conserved cluster of homeodomain binding sites in the mouse Hoxa-4 intron functions in Drosophila embryos as an enhancer that is directly regulated by Ultrabithorax. Haerry, T.E., Gehring, W.J. Dev. Biol. (1997) [Pubmed]
  9. A genetic and developmental analysis of mutations in labial, a gene necessary for proper head formation in Drosophila melanogaster. Merrill, V.K., Diederich, R.J., Turner, F.R., Kaufman, T.C. Dev. Biol. (1989) [Pubmed]
  10. Characterization of the Tribolium Deformed ortholog and its ability to directly regulate Deformed target genes in the rescue of a Drosophila Deformed null mutant. Brown, S., Holtzman, S., Kaufman, T., Denell, R. Dev. Genes Evol. (1999) [Pubmed]
  11. Lox6, a leech Dfd ortholog, is expressed in the central nervous system and in peripheral sensory structures. Wong, V.Y., Macagno, E.R. Dev. Genes Evol. (1998) [Pubmed]
  12. Interchange of DNA-binding modes in the deformed and ultrabithorax homeodomains: a structural role for the N-terminal arm. Frazee, R.W., Taylor, J.A., Tullius, T.D. J. Mol. Biol. (2002) [Pubmed]
  13. Activity regulation of a Hox protein and a role for the homeodomain in inhibiting transcriptional activation. Li, X., Murre, C., McGinnis, W. EMBO J. (1999) [Pubmed]
  14. DEAF-1 function is essential for the early embryonic development of Drosophila. Veraksa, A., Kennison, J., McGinnis, W. Genesis (2002) [Pubmed]
  15. Temperature compensation and temporal expression mediated by an enhancer element in Drosophila. Hoopengardner, B., Helfand, S.L. Mech. Dev. (2002) [Pubmed]
  16. Cross-regulation of Hox genes in the Drosophila melanogaster embryo. Miller, D.F., Rogers, B.T., Kalkbrenner, A., Hamilton, B., Holtzman, S.L., Kaufman, T. Mech. Dev. (2001) [Pubmed]
  17. Antp-type homeodomains have distinct DNA binding specificities that correlate with their different regulatory functions in embryos. Dessain, S., Gross, C.T., Kuziora, M.A., McGinnis, W. EMBO J. (1992) [Pubmed]
  18. Hox genes differentially regulate Serrate to generate segment-specific structures. Wiellette, E.L., McGinnis, W. Development (1999) [Pubmed]
  19. Cap 'n' collar B cooperates with a small Maf subunit to specify pharyngeal development and suppress deformed homeotic function in the Drosophila head. Veraksa, A., McGinnis, N., Li, X., Mohler, J., McGinnis, W. Development (2000) [Pubmed]
  20. Autocatalysis and phenotypic expression of Drosophila homeotic gene Deformed: its dependence on polarity and homeotic gene function. González-Reyes, A., Macías, A., Morata, G. Development (1992) [Pubmed]
  21. Structural changes in the antennapedia complex of Drosophila pseudoobscura. Randazzo, F.M., Seeger, M.A., Huss, C.A., Sweeney, M.A., Cecil, J.K., Kaufman, T.C. Genetics (1993) [Pubmed]
  22. High-affinity binding sites for the Deformed protein are required for the function of an autoregulatory enhancer of the Deformed gene. Regulski, M., Dessain, S., McGinnis, N., McGinnis, W. Genes Dev. (1991) [Pubmed]
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