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Gene Review

tin  -  tinman

Drosophila melanogaster

Synonyms: CG7895, DROHOXHK4, DROHOXNK4, DmNK-4, Dmel\CG7895, ...
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Disease relevance of tin


High impact information on tin

  • Taspase1: a threonine aspartase required for cleavage of MLL and proper HOX gene expression [4].
  • An early and important event in the regional subdivision of the mesoderm is the restriction of tinman expression to dorsal mesodermal cells [5].
  • Early in Drosophila embryogenesis, gap gene products directly repress transcription of homeotic (HOX) genes and thereby delimit HOX expression domains [6].
  • Polycomb response elements (PREs) are specific cis-regulatory sequences needed for transcriptional repression of HOX and other target genes by Polycomb group (PcG) proteins [7].
  • The linear arrangement of the Hox genes on the chromosome correlates with the spatial distribution of HOX protein expression along the anterior-posterior axis of the embryo [8].

Biological context of tin


Anatomical context of tin

  • We show that the binding and synergistic activities of Smad and Tinman proteins are critical for mesodermal tinman induction, whereas repressor binding sites prevent induction in the dorsal ectoderm and amnioserosa [12].
  • We identified a cis-regulatory element in the first intron of dSUR, which contains Tinman consensus binding sites and is sufficient for faithful dSUR expression in the fly's myocardium [14].
  • Both Tin binding sites are required for enhancer activity in all three muscle cell lineages [15].
  • Several vertebrate relatives of tinman, many of which are predominately expressed in the very early cardiac progenitors (and pharyngeal endoderm), also seem to promote heart development [16].
  • We have previously described CEH-22, an NK-2 class homeodomain transcription factor similar to Drosophila tinman and vertebrate Nkx2-5, which is expressed exclusively in the pharyngeal muscles [17].

Associations of tin with chemical compounds


Physical interactions of tin


Regulatory relationships of tin

  • tincar encodes a novel transmembrane protein expressed in the Tinman-expressing cardioblasts of Drosophila [22].
  • Conversely, ectopic expression of ush results in a decrease in the number of cardioblasts in the heart and the inhibition of a cardial cell enhancer normally regulated by the synergistic activity of the Pannier and Tinman cardiogenic factors [23].
  • Tinman regulates the transcription of the beta3 tubulin gene (betaTub60D) in the dorsal vessel of Drosophila [21].

Other interactions of tin

  • By contrast, pan-mesodermal overexpression of pannier ectopically expands tinman expression, whereas overexpression of u-shaped inhibits cardiogenesis [24].
  • We propose that nmr is another determinant of cardiogenesis, along with tinman and pannier [25].
  • The tinc mRNA was expressed specifically in four of the six pairs of cardioblasts in each segment, in a pattern identical to that of tinman (tin), a homeobox gene required for the specification of the dorsal vessel [22].
  • The patterns of wingless, decapentaplegic, and tinman position the Drosophila heart [26].
  • Conversely, the expression of the Dorsocross (Doc) T-box genes, which is normally restricted to the two Tin-negative cardioblasts in each hemisegment, is strongly expanded into the majority of cardioblasts in mid mutant and mid+H15-deficient embryos [27].

Analytical, diagnostic and therapeutic context of tin

  • Here we present a functional dissection of a tinman enhancer that mediates the Dpp response [12].
  • Site-directed mutagenesis of this element shows that these Tinman sites are critical to dSUR expression, and further genetic manipulations suggest that the GATA transcription factor Pannier is synergistically involved in cardiac-restricted dSUR expression in vivo [14].
  • We have isolated a new homeobox-containing gene, msh-2, by means of the polymerase chain reactions (PCR) using redundant primers. msh-2 is specifically expressed in mesodermal primordia during a short time period early in development [28].
  • Using immunoprecipitation and in vitro pull-down assays, we show that NK-4 directly interacts with the Groucho corepressor, for which the homeodomain is required [29].
  • Development of the Drosophila embryonic midgut is dependent on a number of genes, including tinman and bagpipe, which are required for formation of the visceral mesoderm, and the homeotic genes and their targets, which act locally in the visceral mesoderm to direct formation of specific midgut constrictions [30].


  1. Expression of HOX homeogenes in human neuroblastoma cell culture lines. Peverali, F.A., D'Esposito, M., Acampora, D., Bunone, G., Negri, M., Faiella, A., Stornaiuolo, A., Pannese, M., Migliaccio, E., Simeone, A. Differentiation (1990) [Pubmed]
  2. Expression of HOX homeobox genes in the adult human colonic mucosa (and colorectal cancer?). Freschi, G., Taddei, A., Bechi, P., Faiella, A., Gulisano, M., Cillo, C., Bucciarelli, G., Boncinelli, E. Int. J. Mol. Med. (2005) [Pubmed]
  3. Human HOX genes are differentially activated by retinoic acid in embryonal carcinoma cells according to their position within the four loci. Stornaiuolo, A., Acampora, D., Pannese, M., D'Esposito, M., Morelli, F., Migliaccio, E., Rambaldi, M., Faiella, A., Nigro, V., Simeone, A. Cell Differ. Dev. (1990) [Pubmed]
  4. Taspase1: a threonine aspartase required for cleavage of MLL and proper HOX gene expression. Hsieh, J.J., Cheng, E.H., Korsmeyer, S.J. Cell (2003) [Pubmed]
  5. Induction of visceral and cardiac mesoderm by ectodermal Dpp in the early Drosophila embryo. Frasch, M. Nature (1995) [Pubmed]
  6. dMi-2, a hunchback-interacting protein that functions in polycomb repression. Kehle, J., Beuchle, D., Treuheit, S., Christen, B., Kennison, J.A., Bienz, M., Müller, J. Science (1998) [Pubmed]
  7. A Polycomb group protein complex with sequence-specific DNA-binding and selective methyl-lysine-binding activities. Klymenko, T., Papp, B., Fischle, W., Köcher, T., Schelder, M., Fritsch, C., Wild, B., Wilm, M., Müller, J. Genes Dev. (2006) [Pubmed]
  8. Structure of HoxA9 and Pbx1 bound to DNA: Hox hexapeptide and DNA recognition anterior to posterior. LaRonde-LeBlanc, N.A., Wolberger, C. Genes Dev. (2003) [Pubmed]
  9. Nuclear integration of positive Dpp signals, antagonistic Wg inputs and mesodermal competence factors during Drosophila visceral mesoderm induction. Lee, H.H., Frasch, M. Development (2005) [Pubmed]
  10. Molecular integration of inductive and mesoderm-intrinsic inputs governs even-skipped enhancer activity in a subset of pericardial and dorsal muscle progenitors. Knirr, S., Frasch, M. Dev. Biol. (2001) [Pubmed]
  11. Cardiac enhancer activity of the homeobox gene tinman depends on CREB consensus binding sites in Drosophila. Venkatesh, T.V., Park, M., Ocorr, K., Nemaceck, J., Golden, K., Wemple, M., Bodmer, R. Genesis (2000) [Pubmed]
  12. Smad proteins act in combination with synergistic and antagonistic regulators to target Dpp responses to the Drosophila mesoderm. Xu, X., Yin, Z., Hudson, J.B., Ferguson, E.L., Frasch, M. Genes Dev. (1998) [Pubmed]
  13. Synergistic activation of a Drosophila enhancer by HOM/EXD and DPP signaling. Grieder, N.C., Marty, T., Ryoo, H.D., Mann, R.S., Affolter, M. EMBO J. (1997) [Pubmed]
  14. The ATP-sensitive potassium (KATP) channel-encoded dSUR gene is required for Drosophila heart function and is regulated by tinman. Akasaka, T., Klinedinst, S., Ocorr, K., Bustamante, E.L., Kim, S.K., Bodmer, R. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  15. Transcription of the myogenic regulatory gene Mef2 in cardiac, somatic, and visceral muscle cell lineages is regulated by a Tinman-dependent core enhancer. Cripps, R.M., Zhao, B., Olson, E.N. Dev. Biol. (1999) [Pubmed]
  16. Differential rescue of visceral and cardiac defects in Drosophila by vertebrate tinman-related genes. Park, M., Lewis, C., Turbay, D., Chung, A., Chen, J.N., Evans, S., Breitbart, R.E., Fishman, M.C., Izumo, S., Bodmer, R. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  17. The Caenorhabditis elegans NK-2 homeobox gene ceh-22 activates pharyngeal muscle gene expression in combination with pha-1 and is required for normal pharyngeal development. Okkema, P.G., Ha, E., Haun, C., Chen, W., Fire, A. Development (1997) [Pubmed]
  18. Genetically distinct cardial cells within the Drosophila heart. Gajewski, K., Choi, C.Y., Kim, Y., Schulz, R.A. Genesis (2000) [Pubmed]
  19. HOX gene activation by retinoic acid. Boncinelli, E., Simeone, A., Acampora, D., Mavilio, F. Trends Genet. (1991) [Pubmed]
  20. Spontaneous and bleomycin-induced genomic alterations in the progeny of Drosophila treated males depends on the Msh2 status. DNA fingerprinting analysis. López, A., Baida, A., Marcos, R., Xamena, N., Velázquez, A. DNA Repair (Amst.) (2002) [Pubmed]
  21. Tinman regulates the transcription of the beta3 tubulin gene (betaTub60D) in the dorsal vessel of Drosophila. Kremser, T., Gajewski, K., Schulz, R.A., Renkawitz-Pohl, R. Dev. Biol. (1999) [Pubmed]
  22. tincar encodes a novel transmembrane protein expressed in the Tinman-expressing cardioblasts of Drosophila. Hirota, Y., Sawamoto, K., Okano, H. Mech. Dev. (2002) [Pubmed]
  23. The multitype zinc-finger protein U-shaped functions in heart cell specification in the Drosophila embryo. Fossett, N., Zhang, Q., Gajewski, K., Choi, C.Y., Kim, Y., Schulz, R.A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  24. Gata factor Pannier is required to establish competence for heart progenitor formation. Klinedinst, S.L., Bodmer, R. Development (2003) [Pubmed]
  25. Neuromancer Tbx20-related genes (H15/midline) promote cell fate specification and morphogenesis of the Drosophila heart. Qian, L., Liu, J., Bodmer, R. Dev. Biol. (2005) [Pubmed]
  26. The patterns of wingless, decapentaplegic, and tinman position the Drosophila heart. Lockwood, W.K., Bodmer, R. Mech. Dev. (2002) [Pubmed]
  27. Tbx20-related genes, mid and H15, are required for tinman expression, proper patterning, and normal differentiation of cardioblasts in Drosophila. Reim, I., Mohler, J.P., Frasch, M. Mech. Dev. (2005) [Pubmed]
  28. A new homeobox-containing gene, msh-2, is transiently expressed early during mesoderm formation of Drosophila. Bodmer, R., Jan, L.Y., Jan, Y.N. Development (1990) [Pubmed]
  29. The homeodomain transcription factor NK-4 acts as either a transcriptional activator or repressor and interacts with the p300 coactivator and the Groucho corepressor. Choi, C.Y., Lee, Y.M., Kim, Y.H., Park, T., Jeon, B.H., Schulz, R.A., Kim, Y. J. Biol. Chem. (1999) [Pubmed]
  30. Drosophila midgut morphogenesis requires the function of the segmentation gene odd-paired. Cimbora, D.M., Sakonju, S. Dev. Biol. (1995) [Pubmed]
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