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Gene Review

NEFM  -  neurofilament, medium polypeptide

Gallus gallus

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Disease relevance of NEFM


High impact information on NEFM

  • Remarkably, ectopic coexpression of Myb and NF-M proteins in erythroid cells or fibroblasts was sufficient to induce endogenous markers of myeloid differentiation, like the mim-1 and lysozyme genes [2].
  • Here, we investigated the tissue-specific regulation of the mim-1 promoter and found that it not only contains binding sites for Myb but also for NF-M, a myeloid-specific transcription factor that probably corresponds to mammalian C/EBP beta [2].
  • In situ hybridization revealed NF-M mRNA to be highly expressed in regions of the chick central nervous system, which contain multipolar and/or long-projection neurons [3].
  • In addition, a truncated, dominant-negative form of NF-M inhibited cMGF expression in macrophages, indicating that NF-M is required for the normal activation of the gene [1].
  • When multipotent hematopoietic progenitor cells were stimulated to differentiate, NF-M expression was induced at a very early stage, suggesting that the transcription factor plays a role in lineage commitment [1].

Biological context of NEFM

  • The NF-M gene contains two introns which both are located within the highly conserved C-terminal region of the rod domain [4].
  • To functionally analyze the NF-M promoter, constructs carrying 112, 222, and 1026 nucleotides of the 5' upstream region in front of a luciferase reporter gene were tested for their capability to direct luciferase expression after transient transfection into various cell lines [4].
  • The NF-M transcription factor is related to C/EBP beta and plays a role in signal transduction, differentiation and leukemogenesis of avian myelomonocytic cells [1].
  • NF-M stimulates the expression of the gene encoding cMGF, a myeloid cell-specific growth factor, creating an autocrine growth loop crucial to oncogene transformation of myeloid cells [1].
  • Proteolytic cleavage and phosphopeptide mapping of 32P-labeled NF-M from control and treated cultures revealed that the phosphorylation of only one subset of phosphopeptides was affected by staurosporine, K252a, and LiCl [5].

Anatomical context of NEFM

  • However, in spinal cords, there was only NF-M decreased, both of NF-H and NF-L kept unaffected [6].
  • Large numbers of replicating neuroepithelial cells were found to express one of these proteins, NF-M, generations before the existence of any postmitotic neuroblasts (Days 1-2 1/2 of incubation) [7].
  • Two-dimensional gels stained for protein further showed that the highly phosphorylated form of NF-M is transiently lost from embryonic optic nerve in E14, while the less phosphorylated form persists throughout the embryonic developmental stages [8].
  • This transient NF-M expression was found in certain other cells of early embryos, including cardiac myoblasts [7].
  • We have investigated ways of perturbing this process in intact cells and have found that phosphorylation of newly synthesized NF-M in cultured chick sensory neurons is inhibited by Li+ [9].

Associations of NEFM with chemical compounds


Analytical, diagnostic and therapeutic context of NEFM

  • An immunohistochemical survey was carried out on frozen sections of the early embryonic chick brain between 1 and 6 days of incubation, with antisera to the three neurofilament proteins (NF-L, NF-M, NF-H) [7].
  • We also examined their effect on the post-translational mobility shift on SDS-PAGE that accompanies phosphorylation of newly synthesized NF-M [5].


  1. The NF-M transcription factor is related to C/EBP beta and plays a role in signal transduction, differentiation and leukemogenesis of avian myelomonocytic cells. Katz, S., Kowenz-Leutz, E., Müller, C., Meese, K., Ness, S.A., Leutz, A. EMBO J. (1993) [Pubmed]
  2. Myb and NF-M: combinatorial activators of myeloid genes in heterologous cell types. Ness, S.A., Kowenz-Leutz, E., Casini, T., Graf, T., Leutz, A. Genes Dev. (1993) [Pubmed]
  3. Identification of gene products expressed in the developing chick visual system: characterization of a middle-molecular-weight neurofilament cDNA. Zopf, D., Hermans-Borgmeyer, I., Gundelfinger, E.D., Betz, H. Genes Dev. (1987) [Pubmed]
  4. Isolation of the chicken middle-molecular weight neurofilament (NF-M) gene and characterization of its promoter. Zopf, D., Dineva, B., Betz, H., Gundelfinger, E.D. Nucleic Acids Res. (1990) [Pubmed]
  5. Differential sensitivity to inhibitors discriminates between two types of kinases responsible for in vivo phosphorylation of different sites in the carboxy-terminal tail of chicken neurofilament-M. Bennett, G.S., Basu, U., Hollander, B.A., Quintana, R., Rodriguez, R. Mol. Cell. Neurosci. (1994) [Pubmed]
  6. Expression changes of neurofilament subunits in the central nervous system of hens treated with tri-ortho-cresyl phosphate (TOCP). Zhao, X.L., Zhang, T.L., Zhang, C.L., Han, X.Y., Yu, S.F., Li, S.X., Cui, N., Xie, K.Q. Toxicology (2006) [Pubmed]
  7. Transient expression of a neurofilament protein by replicating neuroepithelial cells of the embryonic chick brain. Bennett, G.S., DiLullo, C. Dev. Biol. (1985) [Pubmed]
  8. Developmental changes in phosphorylation state of neurofilament proteins in the chick embryonic optic nerve. Go, M.J., Tanaka, H., Obata, K., Fujita, S.C. Dev. Biol. (1989) [Pubmed]
  9. Lithium chloride inhibits the phosphorylation of newly synthesized neurofilament protein, NF-M, in cultured chick sensory neurons. Bennett, G.S., Laskowska, D., DiLullo, C. J. Neurochem. (1991) [Pubmed]
  10. A unique neurofilament from Torpedo electric lobe: sequence, expression, and localization analysis. Linial, M., Scheller, R.H. J. Neurochem. (1990) [Pubmed]
  11. Alteration in neurofilament axonal transport in the sciatic nerve of the diisopropyl phosphorofluoridate (DFP)-treated hen. Gupta, R.P., Abdel-Rahman, A., Wilmarth, K.W., Abou-Donia, M.B. Biochem. Pharmacol. (1997) [Pubmed]
  12. Altered expression of neurofilament subunits in diisopropyl phosphorofluoridate-treated hen spinal cord and their presence in axonal aggregations. Gupta, R.P., Abdel-Rahman, A., Jensen, K.F., Abou-Donia, M.B. Brain Res. (2000) [Pubmed]
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