The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Gene Review

sim  -  single-minded

Drosophila melanogaster

Synonyms: 0483/09, 0716/08, 0899/14, 0953/08, 1002/10, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of sim

  • We set out to define the holoprosencephaly (HPE) critical region on chromosome 21 and also to determine whether there were human homologues of the Drosophila single-minded (sim) gene that might be involved in HPE [1].
  • As part of our effort to clone genes of human chromosome 21 that may contribute to Down syndrome, we have previously isolated four exons with homology to Drosophila single-minded (sim) gene, which encodes a transcription factor that is a master regulator of fruit fly neurogenesis [2].

High impact information on sim

  • Single-minded and Down syndrome [3]?
  • Induction of ectopic sim protein under the control of the hsp70 promoter shows that sim can direct cells of the lateral CNS to exhibit midline cell morphology and patterns of gene expression [4].
  • Cell fate experiments establish that sim is required for early events in midline cell development, including a synchronized cell division, proper formation of nerve cell precursors, and positive auto-regulation of its midline expression [4].
  • Mutations in the single-minded (sim) gene of Drosophila result in the loss of the precursor cells giving rise to the midline cells of the embryonic central nervous system [5].
  • We have studied the mutant phenotype and expression of a gene, single-minded (sim), which is involved in generating a specific region of this neuroepithelium [6].

Biological context of sim


Anatomical context of sim

  • The ectodermal defects in single minded (sim) mutant embryos, in which the midline fails to develop, suggested that the midline cells contribute to patterning of the ventral ectoderm [12].
  • As shown by pole cell transplantations, spi and S are also required for normal development of the female germ line, while sim, rho, and pnt appear to be exclusively zygotically expressed, and the maternal gene sic acts in the germ line autonomously [13].
  • Additional Sim localization in the medullary and laminar neurons of the optic lobes may correlate with the presence of ectopic axon bundles observed in the optic lobes of sim mutant flies [8].
  • Ectopic expression of sim in the ventral neuroectoderm during the blastoderm stage repressed expression of the three homeodomain genes in the ventral neuroectoderm [14].
  • Confocal imaging of Single-minded and Trachealess protein localization indicate that they accumulate in cell nuclei when initially synthesized in their respective cell lineages and remain nuclear throughout embryogenesis [15].

Associations of sim with chemical compounds

  • PAS is an acronym formed from the names of the Drosophila period clock protein (PER), vertebrate aryl hydrocarbon receptor nuclear translocator (ARNT), and Drosophila single-minded protein (SIM) [16].
  • Three independent activation domains were identified in the carboxy terminal region of Single-minded that include areas rich in serine, threonine, glutamine and proline residues [17].

Physical interactions of sim


Regulatory relationships of sim

  • Thus, Notch signalling appears to relieve the repression exerted by Su(H) and to up-regulate sim transcription in the mesectoderm [18].

Other interactions of sim

  • This positive effect of Sna depends on the Su(H)-binding sites within the sim promoter, suggesting that Sna regulates Notch signaling [7].
  • On the other hand, overexpression of spi and Draf causes ectopic expression of the neuroectodermal markers in the sim mutant [19].
  • RESULTS: In Drosophila embryos, the neural midline marker Single-minded is expressed in foregut cells adjacent to the brain, as are members of the Egf receptor signaling pathway [20].
  • Single-minded, Dmef2, Pointed, and Su(H) act on identified regulatory sequences of the roughest gene in Drosophila melanogaster [21].
  • Loss of jing-lacZ expression in homozygous sim mutants and induction of jing-lacZ by ectopic sim expression establish that jing is part of the CNS midline lineage [22].

Analytical, diagnostic and therapeutic context of sim

  • Sequence analysis shows that sim is a member of the basic-helix-loop-helix class of transcription factors [4].
  • We have identified the sim transcription unit and have shown by in situ hybridization to embryos that the sim gene is expressed specifically in the midline neuroepithelium [6].
  • Furthermore, ectopic transplantations of wild-type midline cells into single minded (sim) mutant embryos suggest that the ventral midline is required for correct positioning of the cells [23].


  1. Physical mapping of the holoprosencephaly critical region in 21q22.3, exclusion of SIM2 as a candidate gene for holoprosencephaly, and mapping of SIM2 to a region of chromosome 21 important for Down syndrome. Muenke, M., Bone, L.J., Mitchell, H.F., Hart, I., Walton, K., Hall-Johnson, K., Ippel, E.F., Dietz-Band, J., Kvaløy, K., Fan, C.M. Am. J. Hum. Genet. (1995) [Pubmed]
  2. Cloning of two human homologs of the Drosophila single-minded gene SIM1 on chromosome 6q and SIM2 on 21q within the Down syndrome chromosomal region. Chrast, R., Scott, H.S., Chen, H., Kudoh, J., Rossier, C., Minoshima, S., Wang, Y., Shimizu, N., Antonarakis, S.E. Genome Res. (1997) [Pubmed]
  3. Single-minded and Down syndrome? Chen, H., Chrast, R., Rossier, C., Gos, A., Antonarakis, S.E., Kudoh, J., Yamaki, A., Shindoh, N., Maeda, H., Minoshima, S. Nat. Genet. (1995) [Pubmed]
  4. The Drosophila single-minded gene encodes a helix-loop-helix protein that acts as a master regulator of CNS midline development. Nambu, J.R., Lewis, J.O., Wharton, K.A., Crews, S.T. Cell (1991) [Pubmed]
  5. The Drosophila single-minded gene encodes a nuclear protein with sequence similarity to the per gene product. Crews, S.T., Thomas, J.B., Goodman, C.S. Cell (1988) [Pubmed]
  6. Molecular genetics of the single-minded locus: a gene involved in the development of the Drosophila nervous system. Thomas, J.B., Crews, S.T., Goodman, C.S. Cell (1988) [Pubmed]
  7. Snail is required for Delta endocytosis and Notch-dependent activation of single-minded expression. Morel, V., Le Borgne, R., Schweisguth, F. Dev. Genes Evol. (2003) [Pubmed]
  8. Novel behavioral and developmental defects associated with Drosophila single-minded. Pielage, J., Steffes, G., Lau, D.C., Parente, B.A., Crews, S.T., Strauss, R., Klämbt, C. Dev. Biol. (2002) [Pubmed]
  9. The Snail repressor positions Notch signaling in the Drosophila embryo. Cowden, J., Levine, M. Development (2002) [Pubmed]
  10. Aryl hydrocarbon or dioxin receptor: biologic and toxic responses. Bock, K.W. Rev. Physiol. Biochem. Pharmacol. (1994) [Pubmed]
  11. cDNA cloning of a murine homologue of Drosophila single-minded, its mRNA expression in mouse development, and chromosome localization. Ema, M., Suzuki, M., Morita, M., Hirose, K., Sogawa, K., Matsuda, Y., Gotoh, O., Saijoh, Y., Fujii, H., Hamada, H., Fujii-Kuriyama, Y. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  12. The Drosophila embryonic midline is the site of Spitz processing, and induces activation of the EGF receptor in the ventral ectoderm. Golembo, M., Raz, E., Shilo, B.Z. Development (1996) [Pubmed]
  13. A group of genes required for pattern formation in the ventral ectoderm of the Drosophila embryo. Mayer, U., Nüsslein-Volhard, C. Genes Dev. (1988) [Pubmed]
  14. CNS midline cells contribute to maintenance of the initial dorsoventral patterning of the Drosophila ventral neuroectoderm. Kim, I.O., Kim, I.C., Kim, S., Kwon, Y.K., Han, P.L., Jeon, S.H., Kim, S.H. J. Neurobiol. (2005) [Pubmed]
  15. Regulation of bHLH-PAS protein subcellular localization during Drosophila embryogenesis. Ward, M.P., Mosher, J.T., Crews, S.T. Development (1998) [Pubmed]
  16. Structure-function relationships of EcDOS, a heme-regulated phosphodiesterase from Escherichia coli. Sasakura, Y., Yoshimura-Suzuki, T., Kurokawa, H., Shimizu, T. Acc. Chem. Res. (2006) [Pubmed]
  17. Transcriptional activation domains of the single-minded bHLH protein are required for CNS midline cell development. Franks, R.G., Crews, S.T. Mech. Dev. (1994) [Pubmed]
  18. Repression by suppressor of hairless and activation by Notch are required to define a single row of single-minded expressing cells in the Drosophila embryo. Morel, V., Schweisguth, F. Genes Dev. (2000) [Pubmed]
  19. The CNS midline cells control the spitz class and Egfr signaling genes to establish the proper cell fate of the Drosophila ventral neuroectoderm. Chang, J., Kim, I.O., Ahn, J.S., Kim, S.H. Int. J. Dev. Biol. (2001) [Pubmed]
  20. A function for Egf receptor signaling in expanding the developing brain in Drosophila. Page, D.T. Curr. Biol. (2003) [Pubmed]
  21. Single-minded, Dmef2, Pointed, and Su(H) act on identified regulatory sequences of the roughest gene in Drosophila melanogaster. Apitz, H., Strünkelnberg, M., de Couet, H.G., Fischbach, K.F. Dev. Genes Evol. (2005) [Pubmed]
  22. The jing Zn-finger transcription factor is a mediator of cellular differentiation in the Drosophila CNS midline and trachea. Sedaghat, Y., Miranda, W.F., Sonnenfeld, M.J. Development (2002) [Pubmed]
  23. Commitment of CNS progenitors along the dorsoventral axis of Drosophila neuroectoderm. Udolph, G., Lüer, K., Bossing, T., Technau, G.M. Science (1995) [Pubmed]
WikiGenes - Universities