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Gene Review

ptc  -  patched

Drosophila melanogaster

Synonyms: BcDNA:RH36596, CG2411, Conf, Dmel\CG2411, Hedgehog receptor, ...
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Disease relevance of ptc


High impact information on ptc

  • Here we present evidence that Patched destabilizes Smoothened in the absence of Hedgehog [5].
  • Their range of action is limited by a C-terminal cholesterol tether and the upregulation of Patched (Ptc) receptor levels [6].
  • Analysis of the mutant phenotype demonstrates that both segment and parasegment borders are included in the duplicated pattern of ptc mutants [7].
  • The pattern of expression does not directly predict the transformation seen in ptc mutant embryos, suggesting that ptc participates in cell interactions that establish pattern within the segment [7].
  • The syndrome results from germline mutations of the human homolog of the drosophila segment polarity gene patched (ptc) [3].

Biological context of ptc

  • A point mutation in the motor domain of Cos2 results in a dominant-negative form of the protein that derepresses dpp but not ptc [8].
  • A single pulse of Patched transgene expression has little or no effect on the segmental pattern, as has been previously reported [9].
  • Finally, we identify sequences in the promoter region of the ptc gene, a primary target of Hh signaling, that are identical to the consensus-binding sequence of the GLI protein and are required for reporter gene expression in response to Hh activity [10].
  • Attenuation of Hh signalling activity caused by loss of fused function results in a striking down-regulation of col, ptc, and engrailed (en) symmetrically about the DV boundary [11].
  • Furthermore, ptcIN is a dominant suppressor of the oro embryonic lethal phenotype, suggesting a close and dose-dependent relationship between oro and ptc in Hh signal transduction. oro function is also required in imaginal development [12].

Anatomical context of ptc

  • G509V exhibits vesicular localisation identical to the wild-type protein, but the C-terminal truncated Patched molecule is localised predominantly to the plasma membrane [13].
  • Sonic Hedgehog (Shh) and Patched (Ptc) were found only in the dorsal tongue epithelium [14].
  • Mutant analysis shows that the lack of ptc activity alters the fate of optic-lobe primordia precursors [15].
  • Sonic hedgehog is also involved in the induction of ventral cell type in the developing somites. ptc is a key gene in the Drosophila hedgehog signaling pathway where it is involved in transducing the hedgehog signal and is also a transcriptional target of the signal [16].
  • We report that 14% of ptc+/- mice develop central nervous system tumors in the posterior fossa by 10 months of age, with peak tumor incidence occurring between 16 and 24 weeks of age [4].

Associations of ptc with chemical compounds

  • Here we present evidence that removing activity of the gene encoding cyclic AMP-dependent protein kinase A (pka) is functionally equivalent to removing ptc activity or to providing cells with the Hh signal [17].
  • Mutations in the sterol-sensing domain of Patched suggest a role for vesicular trafficking in Smoothened regulation [18].

Physical interactions of ptc


Regulatory relationships of ptc

  • High levels of Patched expression might therefore overcome the repression and repress wg in all cells [9].
  • Similarly, patched (ptc) is also ectopically expressed in such posterior compartment en-inv- null clones [21].
  • Hence, mutations within the ptc gene that result in the failure of Ptc to inhibit Smo lead to constitutive activity of the Hh signalling pathway and to cancer, such as basal cell carcinoma [22].
  • The ectopic expression of hh that is normally induced in patched (ptc) mutant embryos does not appear in ptc en double mutants [23].
  • We propose that ptc controls dpp expression in the imaginal discs, and that the restricted expression of dpp near the anterior-posterior compartment boundary is essential to maintain the wild-type morphology of the wing disc [24].

Other interactions of ptc

  • Expression of this reporter construct expands in ptc mutants and responds to hh activity [25].
  • Activity of this element depends on ptc, but it contains no consensus Ci-binding sites [25].
  • patched overexpression causes loss of wingless expression in Drosophila embryos [9].
  • Repression of ptc in the presence of the dominant-negative form of Cos2 requires Su(fu), which is phosphorylated in response to Hh in vivo [8].
  • We show that, at the A/P boundary, Fu kinase activity is involved in the maintenance of high ptc expression and in the induction of late anterior engrailed (en) expression [26].

Analytical, diagnostic and therapeutic context of ptc


  1. The role of the hedgehog/patched signaling pathway in epithelial stem cell proliferation: from fly to human. Parisi, M.J., Lin, H. Cell Res. (1998) [Pubmed]
  2. Hedgehog regulates cell growth and proliferation by inducing Cyclin D and Cyclin E. Duman-Scheel, M., Weng, L., Xin, S., Du, W. Nature (2002) [Pubmed]
  3. Rhabdomyosarcomas and radiation hypersensitivity in a mouse model of Gorlin syndrome. Hahn, H., Wojnowski, L., Zimmer, A.M., Hall, J., Miller, G., Zimmer, A. Nat. Med. (1998) [Pubmed]
  4. The normal patched allele is expressed in medulloblastomas from mice with heterozygous germ-line mutation of patched. Wetmore, C., Eberhart, D.E., Curran, T. Cancer Res. (2000) [Pubmed]
  5. Hedgehog induces opposite changes in turnover and subcellular localization of patched and smoothened. Denef, N., Neubüser, D., Perez, L., Cohen, S.M. Cell (2000) [Pubmed]
  6. Dispatched, a novel sterol-sensing domain protein dedicated to the release of cholesterol-modified hedgehog from signaling cells. Burke, R., Nellen, D., Bellotto, M., Hafen, E., Senti, K.A., Dickson, B.J., Basler, K. Cell (1999) [Pubmed]
  7. The Drosophila patched gene encodes a putative membrane protein required for segmental patterning. Hooper, J.E., Scott, M.P. Cell (1989) [Pubmed]
  8. Differential regulation of Hedgehog target gene transcription by Costal2 and Suppressor of Fused. Ho, K.S., Suyama, K., Fish, M., Scott, M.P. Development (2005) [Pubmed]
  9. patched overexpression causes loss of wingless expression in Drosophila embryos. Schuske, K., Hooper, J.E., Scott, M.P. Dev. Biol. (1994) [Pubmed]
  10. Transcriptional activation of hedgehog target genes in Drosophila is mediated directly by the cubitus interruptus protein, a member of the GLI family of zinc finger DNA-binding proteins. Alexandre, C., Jacinto, A., Ingham, P.W. Genes Dev. (1996) [Pubmed]
  11. Notch and Wingless modulate the response of cells to Hedgehog signalling in the Drosophila wing. Glise, B., Jones, D.L., Ingham, P.W. Dev. Biol. (2002) [Pubmed]
  12. oroshigane, a new segment polarity gene of Drosophila melanogaster, functions in hedgehog signal transduction. Epps, J.L., Jones, J.B., Tanda, S. Genetics (1997) [Pubmed]
  13. Functional analysis in Drosophila indicates that the NBCCS/PTCH1 mutation G509V results in activation of smoothened through a dominant-negative mechanism. Hime, G.R., Lada, H., Fietz, M.J., Gillies, S., Passmore, A., Wicking, C., Wainwright, B.J. Dev. Dyn. (2004) [Pubmed]
  14. Molecular and cellular analysis of embryonic avian tongue development. Huang, R., Lang, E.R., Otto, W.R., Christ, B., Patel, K. Anat. Embryol. (2001) [Pubmed]
  15. Chromophore-assisted laser inactivation of patched protein switches cell fate in the larval visual system of Drosophila. Schmucker, D., Su, A.L., Beermann, A., Jäckle, H., Jay, D.G. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  16. Regulation of patched by sonic hedgehog in the developing neural tube. Marigo, V., Tabin, C.J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  17. Signal transduction by cAMP-dependent protein kinase A in Drosophila limb patterning. Lepage, T., Cohen, S.M., Diaz-Benjumea, F.J., Parkhurst, S.M. Nature (1995) [Pubmed]
  18. Mutations in the sterol-sensing domain of Patched suggest a role for vesicular trafficking in Smoothened regulation. Strutt, H., Thomas, C., Nakano, Y., Stark, D., Neave, B., Taylor, A.M., Ingham, P.W. Curr. Biol. (2001) [Pubmed]
  19. In vivo evidence that Patched and Smoothened constitute distinct binding and transducing components of a Hedgehog receptor complex. Chen, Y., Struhl, G. Development (1998) [Pubmed]
  20. Reading the Hedgehog morphogen gradient by measuring the ratio of bound to unbound Patched protein. Casali, A., Struhl, G. Nature (2004) [Pubmed]
  21. Drawing a stripe in Drosophila imaginal disks: negative regulation of decapentaplegic and patched expression by engrailed. Sanicola, M., Sekelsky, J., Elson, S., Gelbart, W.M. Genetics (1995) [Pubmed]
  22. Hedgehog and its patched-smoothened receptor complex: a novel signalling mechanism at the cell surface. Alcedo, J., Noll, M. Biol. Chem. (1997) [Pubmed]
  23. The Drosophila hedgehog gene is expressed specifically in posterior compartment cells and is a target of engrailed regulation. Tabata, T., Eaton, S., Kornberg, T.B. Genes Dev. (1992) [Pubmed]
  24. The Drosophila segment polarity gene patched interacts with decapentaplegic in wing development. Capdevila, J., Estrada, M.P., Sánchez-Herrero, E., Guerrero, I. EMBO J. (1994) [Pubmed]
  25. Expression of wingless in the Drosophila embryo: a conserved cis-acting element lacking conserved Ci-binding sites is required for patched-mediated repression. Lessing, D., Nusse, R. Development (1998) [Pubmed]
  26. Modulation of Hedgehog target gene expression by the Fused serine-threonine kinase in wing imaginal discs. Alves, G., Limbourg-Bouchon, B., Tricoire, H., Brissard-Zahraoui, J., Lamour-Isnard, C., Busson, D. Mech. Dev. (1998) [Pubmed]
  27. The sonic hedgehog receptor patched associates with caveolin-1 in cholesterol-rich microdomains of the plasma membrane. Karpen, H.E., Bukowski, J.T., Hughes, T., Gratton, J.P., Sessa, W.C., Gailani, M.R. J. Biol. Chem. (2001) [Pubmed]
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