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Gene Review

hth  -  homothorax

Drosophila melanogaster

Synonyms: 1323/07, 1422/04, CG17117, Dm-HTH, Dmel\CG17117, ...
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High impact information on hth

  • Homothorax increases rhabdomere size and uncouples R7-R8 communication to allow both cells to express the same opsin rather than different ones as required for color vision [1].
  • Homothorax switches function of Drosophila photoreceptors from color to polarized light sensors [1].
  • MEIS1 is able to rescue hth mutant phenotypes and can induce the cytoplasmic-to-nuclear translocation of EXD in cell culture and Drosophila embryos [2].
  • Taken together, these data indicate that hth is an antennal selector gene, and that Antp promotes leg development by repressing hth and consequently nuclear Exd [3].
  • Thus, alternative splicing of hth results in the generation of multiple transcription factors that execute unique functions in vivo [4].

Biological context of hth

  • Here we show that the PNS phenotype of exd mutant embryos is virtually indistinguishable from that of hth mutant embryos and does not simply follow the homeotic transformations observed in the epidermis [5].
  • The hth gene is expressed throughout embryonic development in a spatially restricted pattern, which is modulated in abdominal segments by abd-A and Ubx [5].
  • We have generated multiple mutations in the hth locus and cloned the hth gene. hth encodes a homeodomain-containing protein that is most similar to the murine proto-oncogene meis1 [5].
  • Ectopic hth expression in the distal leg results in JNK-mediated apoptosis, decreased growth and pattern abnormalities [6].
  • In cells expressing hth in the distal leg, there is a debilitation of the Dpp pathway which is reflected in lower levels of Mad phosphorylation and in increased levels of the receptor thick veins [6].

Anatomical context of hth

  • Regulation and function of Scr, exd, and hth in the Drosophila salivary gland [7].
  • Patterning function of homothorax/extradenticle in the thorax of Drosophila [8].
  • Further, we demonstrate that hth also limits where along the D/V compartment boundary wing blade development can initiate, thus helping to define the size and position of the wing blade within the disc epithelium [9].
  • By analyzing the subcellular localization of Exd deletion mutants in imaginal discs and cultured cells, we identified three elements in Exd, a putative NES, a nuclear localization sequence (NLS), and a region required for Hth-mediated nuclear localization [10].
  • Our results define two functions of Meis during zebrafish hindbrain segmentation: that of a DNA-binding partner of Pbx proteins, and that of a post-transcriptional regulator of Pbx protein levels [11].

Associations of hth with chemical compounds

  • HTH binds to DNA as part of a HTH/Hox/EXD trimeric complex, and we show that this complex is essential for the activation of a natural Hox target enhancer [12].
  • Members of the Meis1 family contain one tryptophan residue amino-terminal to the homeodomain, but site-directed mutagenesis indicates that this residue is not required for cooperative CRS1 binding with Pbx [13].

Physical interactions of hth


Regulatory relationships of hth

  • Wg and Dpp do not act through Dll to repress Hth [15].
  • In contrast to its repressing role in the wing pouch, wg upregulates hth expression in the hinge [16].
  • Clones of cells expressing escargot or homothorax placed in the distal domain induce intercalary expression of dachshund in surrounding cells and reorient planar cell polarity of those cells [17].
  • Coexpression of Distal-less and homothorax activates ectopic spalt expression and can induce the formation of ectopic antennae at novel locations in the body, including the head, the legs, the wings and the genital disc derivatives [18].
  • 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 [9].

Other interactions of hth

  • We suggest that hth acts with exd to delimit the eye field and prevent inappropriate eye development [19].
  • Furthermore, there is a reciprocal repression exerted by HTH on these and other DPP and WG downstream targets that restricts their expression to non-hth-expressing cells [20].
  • Mutations in the hth gene seem to alter the identity of the abdominal chordotonal neurons, which depend on Abd-A for their normal development [5].
  • (i) Clonal ectopic overexpression of ANTP did not repress the expression of the arista determining protein Homothorax (HTH) in early 3rd stadium antennal imaginal discs [21].
  • Differing strategies for the establishment and maintenance of teashirt and homothorax repression in the Drosophila wing [22].

Analytical, diagnostic and therapeutic context of hth

  • A member of a second mammalian homeodomain family, Meis1, is now also demonstrated to be a CRS1-binding protein upon purification using CRS1 affinity chromatography [13].
  • Real-time quantitative PCR analysis of different hth splice isoforms and Northern blotting showed that the conserved element is associated with a high incidence of intron retention in hth pre-mRNA, suggesting that the conserved intronic element is critically important in the post-transcriptional regulation of hth expression in Diptera [23].


  1. Homothorax switches function of Drosophila photoreceptors from color to polarized light sensors. Wernet, M.F., Labhart, T., Baumann, F., Mazzoni, E.O., Pichaud, F., Desplan, C. Cell (2003) [Pubmed]
  2. Nuclear translocation of extradenticle requires homothorax, which encodes an extradenticle-related homeodomain protein. Rieckhof, G.E., Casares, F., Ryoo, H.D., Abu-Shaar, M., Mann, R.S. Cell (1997) [Pubmed]
  3. Control of antennal versus leg development in Drosophila. Casares, F., Mann, R.S. Nature (1998) [Pubmed]
  4. Distinct functions of homeodomain-containing and homeodomain-less isoforms encoded by homothorax. Noro, B., Culi, J., McKay, D.J., Zhang, W., Mann, R.S. Genes Dev. (2006) [Pubmed]
  5. Dorsotonals/homothorax, the Drosophila homologue of meis1, interacts with extradenticle in patterning of the embryonic PNS. Kurant, E., Pai, C.Y., Sharf, R., Halachmi, N., Sun, Y.H., Salzberg, A. Development (1998) [Pubmed]
  6. Distinct functions of homothorax in leg development in Drosophila. Azpiazu, N., Morata, G. Mech. Dev. (2002) [Pubmed]
  7. Regulation and function of Scr, exd, and hth in the Drosophila salivary gland. Henderson, K.D., Andrew, D.J. Dev. Biol. (2000) [Pubmed]
  8. Patterning function of homothorax/extradenticle in the thorax of Drosophila. Aldaz, S., Morata, G., Azpiazu, N. Development (2005) [Pubmed]
  9. A dual role for homothorax in inhibiting wing blade development and specifying proximal wing identities in Drosophila. Casares, F., Mann, R.S. Development (2000) [Pubmed]
  10. Control of the nuclear localization of Extradenticle by competing nuclear import and export signals. Abu-Shaar, M., Ryoo, H.D., Mann, R.S. Genes Dev. (1999) [Pubmed]
  11. Zebrafish Meis functions to stabilize Pbx proteins and regulate hindbrain patterning. Waskiewicz, A.J., Rikhof, H.A., Hernandez, R.E., Moens, C.B. Development (2001) [Pubmed]
  12. Regulation of Hox target genes by a DNA bound Homothorax/Hox/Extradenticle complex. Ryoo, H.D., Marty, T., Casares, F., Affolter, M., Mann, R.S. Development (1999) [Pubmed]
  13. Members of the meis1 and pbx homeodomain protein families cooperatively bind a cAMP-responsive sequence (CRS1) from bovine CYP17. Bischof, L.J., Kagawa, N., Moskow, J.J., Takahashi, Y., Iwamatsu, A., Buchberg, A.M., Waterman, M.R. J. Biol. Chem. (1998) [Pubmed]
  14. Recognition of distinct target sites by a unique Labial/Extradenticle/Homothorax complex. Ebner, A., Cabernard, C., Affolter, M., Merabet, S. Development (2005) [Pubmed]
  15. 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]
  16. Function and regulation of homothorax in the wing imaginal disc of Drosophila. Azpiazu, N., Morata, G. Development (2000) [Pubmed]
  17. Proximal to distal cell communication in the Drosophila leg provides a basis for an intercalary mechanism of limb patterning. Goto, S., Hayashi, S. Development (1999) [Pubmed]
  18. Coexpression of the homeobox genes Distal-less and homothorax determines Drosophila antennal identity. Dong, P.D., Chu, J., Panganiban, G. Development (2000) [Pubmed]
  19. The Homothorax homeoprotein activates the nuclear localization of another homeoprotein, extradenticle, and suppresses eye development in Drosophila. Pai, C.Y., Kuo, T.S., Jaw, T.J., Kurant, E., Chen, C.T., Bessarab, D.A., Salzberg, A., Sun, Y.H. Genes Dev. (1998) [Pubmed]
  20. Generation of multiple antagonistic domains along the proximodistal axis during Drosophila leg development. Abu-Shaar, M., Mann, R.S. Development (1998) [Pubmed]
  21. Tarsus determination in Drosophila melanogaster. Percival-Smith, A., Teft, W.A., Barta, J.L. Genome (2005) [Pubmed]
  22. Differing strategies for the establishment and maintenance of teashirt and homothorax repression in the Drosophila wing. Zirin, J.D., Mann, R.S. Development (2004) [Pubmed]
  23. Ultraconserved elements in insect genomes: a highly conserved intronic sequence implicated in the control of homothorax mRNA splicing. Glazov, E.A., Pheasant, M., McGraw, E.A., Bejerano, G., Mattick, J.S. Genome Res. (2005) [Pubmed]
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