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Gene Review

trh  -  trachealess

Drosophila melanogaster

Synonyms: 3.1, BP1081, CG13885, CG42865, CG6883, ...
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Disease relevance of trh


High impact information on trh

  • A single 3.1 kb Pax 1 (paired box gene) transcript was detected during embryonic development, whereas no transcripts were detected in adult tissues [2].
  • The 3.1 angstrom crystal structure reveals a bound phosphate and patches of positive charge, which may represent the lipopolysaccharide binding site, and a new and unexpected arrangement of four immunoglobulin-like domains forming a horseshoe [3].
  • The RhoGAP crossveinless-c links trachealess and EGFR signaling to cell shape remodeling in Drosophila tracheal invagination [4].
  • Trachealess (Trh) and Single-minded (Sim) are highly similar Drosophila bHLH/PAS transcription factors [5].
  • In trh mutants, tube-forming cells of the salivary gland, trachea, and filzkörper fail to invaginate to form tubes and remain on the embryo surface [6].

Biological context of trh


Anatomical context of trh

  • FKH, in turn, represses trachealess (trh), a duct-specific gene initially expressed throughout the salivary gland primordium. trh encodes a basic helix-loop-helix PAS-domain containing transcription factor that has been proposed to specify the salivary duct fate [12].
  • Expression is first induced by exogenous cues and is subsequently autoregulated. trh is also expressed and required in the posterior spiracles and the salivary gland ducts [13].
  • Ectopic expression experiments show that Single-minded and Trachealess are localized to nuclei in cells throughout the ectoderm and mesoderm, indicating that nuclear accumulation is not regulated in a cell-specific fashion and unlikely to be ligand dependent [11].
  • Using a human probe, two major transcripts (6.1 and 3.1 kb) were identified in mouse and expression was detected in situ in several regions of the mouse brain, including the olfactory bulb, the cerebellum, the cerebral cortex, the pyramidal cell layer of the hippocampus and several hypothalamic nuclei [14].
  • At 10 nm indention, the effective transverse stiffness (K( perpendicular)) of myofibrils in rigor solution (ATP-free, pCa 4.5) was 10.3 +/- 5.0 pN nm(-1) (mean +/- SEM, n = 8); in activating solution (pCa 4.5), 5.9 +/- 3.1 pN nm(-1); and in relaxing solution (pCa 8), 4.4 +/- 2.0 pN nm(-1) [15].

Associations of trh with chemical compounds

  • 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 [16].
  • The degree of inhibition of Ca2+ inflow by primaquine was halved when the extracellular concentration of Ca2+ was increased from 3.1 to 12.5 mM [17].

Physical interactions of trh


Regulatory relationships of trh

  • The Drosophila dysfusion basic helix-loop-helix (bHLH)-PAS gene controls tracheal fusion and levels of the trachealess bHLH-PAS protein [7].
  • Furthermore, ectopic expression of both Trh and Dfr (but not each one alone) triggered trh autoregulation in several embryonic tissues [19].
  • We also determined that the caudal promoter activity can be regulated by Trachealess (Trh)/Tango (Tgo) bHLH-PAS proteins, via the CME sites [20].

Other interactions of trh

  • The lineage-specific action of Single-minded and Trachealess derives from transcriptional activation of their genes in their respective lineages, not from extracellular signaling [11].
  • We present a model proposing that trachealess is the crucial duct-specific gene that Fork head represses to distinguish pregland from preduct cells [21].
  • After the initial establishment of the salivary primordium by Sex combs reduced, fork head excludes eye gone expression from the pregland cells so that its salivary expression is restricted to the posterior preduct cells. trachealess, in contrast, activates eye gone expression in the posterior preduct cells [22].
  • On the other hand, the incidence of misrouted axons is significantly increased, most strongly in the trh, twi double mutant [23].
  • Applying a combined genetic and biochemical approach has led to the identification of a new protein kinase B/Akt target, the transcription factor Trachealess [24].

Analytical, diagnostic and therapeutic context of trh


  1. Evaluation of the antibacterial spectrum of drosocin analogues. Bikker, F.J., Kaman-van Zanten, W.E., de Vries-van de Ruit, A.M., Voskamp-Visser, I., van Hooft, P.A., Mars-Groenendijk, R.H., de Visser, P.C., Noort, D. Chemical biology & drug design. (2006) [Pubmed]
  2. Pax 1, a member of a paired box homologous murine gene family, is expressed in segmented structures during development. Deutsch, U., Dressler, G.R., Gruss, P. Cell (1988) [Pubmed]
  3. Crystal structure of hemolin: a horseshoe shape with implications for homophilic adhesion. Su, X.D., Gastinel, L.N., Vaughn, D.E., Faye, I., Poon, P., Bjorkman, P.J. Science (1998) [Pubmed]
  4. The RhoGAP crossveinless-c links trachealess and EGFR signaling to cell shape remodeling in Drosophila tracheal invagination. Brodu, V., Casanova, J. Genes Dev. (2006) [Pubmed]
  5. The PAS domain confers target gene specificity of Drosophila bHLH/PAS proteins. Zelzer, E., Wappner, P., Shilo, B.Z. Genes Dev. (1997) [Pubmed]
  6. Tubulogenesis in Drosophila: a requirement for the trachealess gene product. Isaac, D.D., Andrew, D.J. Genes Dev. (1996) [Pubmed]
  7. The Drosophila dysfusion basic helix-loop-helix (bHLH)-PAS gene controls tracheal fusion and levels of the trachealess bHLH-PAS protein. Jiang, L., Crews, S.T. Mol. Cell. Biol. (2003) [Pubmed]
  8. Analysis of the transcriptional activation domain of the Drosophila tango bHLH-PAS transcription factor. Sonnenfeld, M.J., Delvecchio, C., Sun, X. Dev. Genes Evol. (2005) [Pubmed]
  9. Mutations that alter the morphology of the malpighian tubules in Drosophila. Jack, J., Myette, G. Dev. Genes Evol. (1999) [Pubmed]
  10. Dysfusion transcriptional control of Drosophila tracheal migration, adhesion, and fusion. Jiang, L., Crews, S.T. Mol. Cell. Biol. (2006) [Pubmed]
  11. Regulation of bHLH-PAS protein subcellular localization during Drosophila embryogenesis. Ward, M.P., Mosher, J.T., Crews, S.T. Development (1998) [Pubmed]
  12. Specification of cell fates within the salivary gland primordium. Haberman, A.S., Isaac, D.D., Andrew, D.J. Dev. Biol. (2003) [Pubmed]
  13. trachealess encodes a bHLH-PAS protein that is an inducer of tracheal cell fates in Drosophila. Wilk, R., Weizman, I., Shilo, B.Z. Genes Dev. (1996) [Pubmed]
  14. A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal regions affected in Down syndrome and maps to the critical region. Guimerá, J., Casas, C., Pucharcòs, C., Solans, A., Domènech, A., Planas, A.M., Ashley, J., Lovett, M., Estivill, X., Pritchard, M.A. Hum. Mol. Genet. (1996) [Pubmed]
  15. Morphology and transverse stiffness of Drosophila myofibrils measured by atomic force microscopy. Nyland, L.R., Maughan, D.W. Biophys. J. (2000) [Pubmed]
  16. 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]
  17. Store-activated Ca2+ inflow in Xenopus laevis oocytes: inhibition by primaquine and evaluation of the role of membrane fusion. Gregory, R.B., Barritt, G.J. Biochem. J. (1996) [Pubmed]
  18. Transcriptional regulation of breathless FGF receptor gene by binding of TRACHEALESS/dARNT heterodimers to three central midline elements in Drosophila developing trachea. Ohshiro, T., Saigo, K. Development (1997) [Pubmed]
  19. Interaction between the bHLH-PAS protein Trachealess and the POU-domain protein Drifter, specifies tracheal cell fates. Zelzer, E., Shilo, B.Z. Mech. Dev. (2000) [Pubmed]
  20. Transcriptional regulation of the Drosophila caudal homeobox gene by bHLH-PAS proteins. Choi, Y.J., Kwon, E.J., Park, J.S., Kang, H.S., Kim, Y.S., Yoo, M.A. Biochim. Biophys. Acta (2007) [Pubmed]
  21. Salivary duct determination in Drosophila: roles of the EGF receptor signalling pathway and the transcription factors fork head and trachealess. Kuo, Y.M., Jones, N., Zhou, B., Panzer, S., Larson, V., Beckendorf, S.K. Development (1996) [Pubmed]
  22. The Drosophila Pax gene eye gone is required for embryonic salivary duct development. Jones, N.A., Kuo, Y.M., Sun, Y.H., Beckendorf, S.K. Development (1998) [Pubmed]
  23. The role of the tracheae and musculature during pathfinding of Drosophila embryonic sensory axons. Younossi-Hartenstein, A., Hartenstein, V. Dev. Biol. (1993) [Pubmed]
  24. Trachealess--a new transcription factor target for PKB/Akt. Downward, J., Leevers, S.J. Dev. Cell (2001) [Pubmed]
  25. Embryonic silk gland development in Bombyx: molecular cloning and expression of the Bombyx trachealess gene. Matsunami, K., Kokubo, H., Ohno, K., Xu, P., Ueno, K., Suzuki, Y. Dev. Genes Evol. (1999) [Pubmed]
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