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Gene Review

Twist1  -  twist basic helix-loop-helix transcription...

Mus musculus

Synonyms: AA960487, M-Twist, M-twist, Pde, Pluridigite, ...
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Disease relevance of Twist1

  • Autosomal dominant mutations in the gene encoding the basic helix-loop-helix transcription factor Twist1 are associated with limb and craniofacial defects in humans with Saethre-Chotzen syndrome [1].
  • In Twist1(+/-) mice with coronal synostosis, we found that the frontal-parietal boundary is defective [2].
  • These results establish a mechanistic link between Twist, EMT, and tumor metastasis [3].
  • Mice homozygous for a twist-2 null allele or doubly heterozygous for twist-1 and -2 alleles show elevated expression of proinflammatory cytokines, resulting in perinatal death from cachexia [4].
  • Furthermore, Twist was inappropriately expressed in 50% of rhabdomyosarcomas, a tumor that arises from skeletal muscle precursors that fail to differentiate [5].
  • We suggest that the failure of this process in Twist1 and EphA4 mutants is the cause of craniosynostosis [6].

Psychiatry related information on Twist1

  • Loss of either of these regions renders Twist less efficient and more similar to Id [7].

High impact information on Twist1

  • Altered Twist1 and Hand2 dimerization is associated with Saethre-Chotzen syndrome and limb abnormalities [1].
  • Dimerization partner choice by Twist1 and Hand2 can be modulated by protein kinase A- and protein phosphatase 2A-regulated phosphorylation of conserved helix I residues [1].
  • Suppression of Twist expression in highly metastatic mammary carcinoma cells specifically inhibits their ability to metastasize from the mammary gland to the lung [3].
  • Twist-1 and -2 repress cytokine gene expression through interaction with RelA [4].
  • The Twist gene product is a transcription factor containing a basic helix-loop-helix (b-HLH) domain, required in head mesenchyme for cranial neural tube morphogenesis in mice [8].

Biological context of Twist1


Anatomical context of Twist1

  • Twist1 dimer selection regulates cranial suture patterning and fusion [12].
  • We also carried out a detailed expression analysis of the helix-loop-helix factors (HLH) Twist and Id1 during calvaria and suture development (E10-P6) [13].
  • Loss of Twist gene function arrests the growth of the limb bud shortly after its formation [14].
  • Development of the hindlimb buds in Twist(-/-) embryos is also retarded [14].
  • Thus, relief of inhibition by Twist proteins is a mandatory event precluding osteoblast differentiation [11].

Associations of Twist1 with chemical compounds


Physical interactions of Twist1

  • These findings demonstrate that M-Twist interacts with MyoD through the basic domains, thereby inhibiting MyoD [17].

Regulatory relationships of Twist1


Other interactions of Twist1


Analytical, diagnostic and therapeutic context of Twist1


  1. Altered Twist1 and Hand2 dimerization is associated with Saethre-Chotzen syndrome and limb abnormalities. Firulli, B.A., Krawchuk, D., Centonze, V.E., Vargesson, N., Virshup, D.M., Conway, S.J., Cserjesi, P., Laufer, E., Firulli, A.B. Nat. Genet. (2005) [Pubmed]
  2. Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis. Merrill, A.E., Bochukova, E.G., Brugger, S.M., Ishii, M., Pilz, D.T., Wall, S.A., Lyons, K.M., Wilkie, A.O., Maxson, R.E. Hum. Mol. Genet. (2006) [Pubmed]
  3. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Yang, J., Mani, S.A., Donaher, J.L., Ramaswamy, S., Itzykson, R.A., Come, C., Savagner, P., Gitelman, I., Richardson, A., Weinberg, R.A. Cell (2004) [Pubmed]
  4. Twist regulates cytokine gene expression through a negative feedback loop that represses NF-kappaB activity. Sosić, D., Richardson, J.A., Yu, K., Ornitz, D.M., Olson, E.N. Cell (2003) [Pubmed]
  5. Twist is a potential oncogene that inhibits apoptosis. Maestro, R., Dei Tos, A.P., Hamamori, Y., Krasnokutsky, S., Sartorelli, V., Kedes, L., Doglioni, C., Beach, D.H., Hannon, G.J. Genes Dev. (1999) [Pubmed]
  6. EphA4 as an effector of Twist1 in the guidance of osteogenic precursor cells during calvarial bone growth and in craniosynostosis. Ting, M.C., Wu, N.L., Roybal, P.G., Sun, J., Liu, L., Yen, Y., Maxson, R.E. Development (2009) [Pubmed]
  7. Repression of muscle-specific gene activation by the murine Twist protein. Hebrok, M., Füchtbauer, A., Füchtbauer, E.M. Exp. Cell Res. (1997) [Pubmed]
  8. Mutations of the TWIST gene in the Saethre-Chotzen syndrome. el Ghouzzi, V., Le Merrer, M., Perrin-Schmitt, F., Lajeunie, E., Benit, P., Renier, D., Bourgeois, P., Bolcato-Bellemin, A.L., Munnich, A., Bonaventure, J. Nat. Genet. (1997) [Pubmed]
  9. Whole genomewide linkage screen for neural tube defects reveals regions of interest on chromosomes 7 and 10. Rampersaud, E., Bassuk, A.G., Enterline, D.S., George, T.M., Siegel, D.G., Melvin, E.C., Aben, J., Allen, J., Aylsworth, A., Brei, T., Bodurtha, J., Buran, C., Floyd, L.E., Hammock, P., Iskandar, B., Ito, J., Kessler, J.A., Lasarsky, N., Mack, P., Mackey, J., McLone, D., Meeropol, E., Mehltretter, L., Mitchell, L.E., Oakes, W.J., Nye, J.S., Powell, C., Sawin, K., Stevenson, R., Walker, M., West, S.G., Worley, G., Gilbert, J.R., Speer, M.C. J. Med. Genet. (2005) [Pubmed]
  10. Expression patterns of Twist and Fgfr1, -2 and -3 in the developing mouse coronal suture suggest a key role for twist in suture initiation and biogenesis. Johnson, D., Iseki, S., Wilkie, A.O., Morriss-Kay, G.M. Mech. Dev. (2000) [Pubmed]
  11. A twist code determines the onset of osteoblast differentiation. Bialek, P., Kern, B., Yang, X., Schrock, M., Sosic, D., Hong, N., Wu, H., Yu, K., Ornitz, D.M., Olson, E.N., Justice, M.J., Karsenty, G. Dev. Cell (2004) [Pubmed]
  12. Twist1 dimer selection regulates cranial suture patterning and fusion. Connerney, J., Andreeva, V., Leshem, Y., Muentener, C., Mercado, M.A., Spicer, D.B. Dev. Dyn. (2006) [Pubmed]
  13. Integration of FGF and TWIST in calvarial bone and suture development. Rice, D.P., Aberg, T., Chan, Y., Tang, Z., Kettunen, P.J., Pakarinen, L., Maxson, R.E., Thesleff, I. Development (2000) [Pubmed]
  14. Twist plays an essential role in FGF and SHH signal transduction during mouse limb development. O'Rourke, M.P., Soo, K., Behringer, R.R., Hui, C.C., Tam, P.P. Dev. Biol. (2002) [Pubmed]
  15. Controlled conversion of an immortalized mesodermal progenitor cell towards osteogenic, chondrogenic, or adipogenic pathways. Poliard, A., Nifuji, A., Lamblin, D., Plee, E., Forest, C., Kellermann, O. J. Cell Biol. (1995) [Pubmed]
  16. Messenger RNA expression of periostin and Twist transiently decrease by occlusal hypofunction in mouse periodontal ligament. Afanador, E., Yokozeki, M., Oba, Y., Kitase, Y., Takahashi, T., Kudo, A., Moriyama, K. Arch. Oral Biol. (2005) [Pubmed]
  17. The basic domain of myogenic basic helix-loop-helix (bHLH) proteins is the novel target for direct inhibition by another bHLH protein, Twist. Hamamori, Y., Wu, H.Y., Sartorelli, V., Kedes, L. Mol. Cell. Biol. (1997) [Pubmed]
  18. M-twist expression inhibits mouse embryonic stem cell-derived myogenic differentiation in vitro. Rohwedel, J., Horák, V., Hebrok, M., Füchtbauer, E.M., Wobus, A.M. Exp. Cell Res. (1995) [Pubmed]
  19. Twist is up-regulated in response to Wnt1 and inhibits mouse mammary cell differentiation. Howe, L.R., Watanabe, O., Leonard, J., Brown, A.M. Cancer Res. (2003) [Pubmed]
  20. A conserved noncoding intronic transcript at the mouse Dnm3 locus. Loebel, D.A., Tsoi, B., Wong, N., Tam, P.P. Genomics (2005) [Pubmed]
  21. Mouse Twist is required for fibroblast growth factor-mediated epithelial-mesenchymal signalling and cell survival during limb morphogenesis. Zuniga, A., Quillet, R., Perrin-Schmitt, F., Zeller, R. Mech. Dev. (2002) [Pubmed]
  22. A twisted hand: bHLH protein phosphorylation and dimerization regulate limb development. Cai, J., Jabs, E.W. Bioessays (2005) [Pubmed]
  23. The M-twist gene of Mus is expressed in subsets of mesodermal cells and is closely related to the Xenopus X-twi and the Drosophila twist genes. Wolf, C., Thisse, C., Stoetzel, C., Thisse, B., Gerlinger, P., Perrin-Schmitt, F. Dev. Biol. (1991) [Pubmed]
  24. Twist function is required for the morphogenesis of the cephalic neural tube and the differentiation of the cranial neural crest cells in the mouse embryo. Soo, K., O'Rourke, M.P., Khoo, P.L., Steiner, K.A., Wong, N., Behringer, R.R., Tam, P.P. Dev. Biol. (2002) [Pubmed]
  25. Isolation of differentially expressed genes from wild-type and Twist mutant mouse limb buds. Loebel, D.A., O'Rourke, M.P., Steiner, K.A., Banyer, J., Tam, P.P. Genesis (2002) [Pubmed]
  26. Twist is required for patterning the cranial nerves and maintaining the viability of mesodermal cells. Ota, M.S., Loebel, D.A., O'Rourke, M.P., Wong, N., Tsoi, B., Tam, P.P. Dev. Dyn. (2004) [Pubmed]
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