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Gene Review

mam  -  mastermind

Drosophila melanogaster

Synonyms: CG8118, Dm0064, Dmel\CG8118, MAM, Mam, ...
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Disease relevance of mam

  • We show that Mastermind plays a similar role in the neurons derived from ganglion mother cells 1-1a and 4-2a, where it specifies the pCC and RP2sib fates, respectively [1].

High impact information on mam

  • Here we identify a new mechanism for disrupting Notch signaling in human tumorigenesis, characterized by altered function of a new ortholog of the Drosophila melanogaster Notch co-activator molecule Mastermind [2].
  • NICD associates with Suppressor of Hairless [Su(H)], a DNA binding protein, and Mastermind (Mam), a transcriptional coactivator [7-9] [3].
  • When expressed in the notum, truncated Mam results in failure of lateral inhibition within proneural clusters and perturbations in cell fate specification within the sensory organ precursor cell lineage [4].
  • To address these questions, we have constructed truncated versions of the Mam protein that elicit dominant phenotypes when expressed in imaginal tissues under GAL4-UAS regulation [4].
  • This suggests that Notch signalling through Mastermind plays a wider role in specifying neuronal identity in the Drosophila central nervous system [1].

Biological context of mam

  • Loss of function for mam also results in a severe neurogenic phenotype [5].
  • Furthermore, Drosophila Mam forms a similar complex with the intracellular domain of Drosophila Notch and Drosophila CSL protein during activation of Enhancer of split, the Drosophila counterpart of HES [6].
  • Immunohistochemical detection of Mam on polytene chromosomes revealed binding at > 100 sites [7].
  • Mam is expressed through all germlayers during early embryogenesis, including ectodermal precursors to both neuroblasts and epidermoblasts [7].
  • In combination with the intracellular domain of Notch and Suppressor of Hairless, Mam forms a transcriptional activation complex [8].

Anatomical context of mam

  • Here it is demonstrated that during early embryogenesis mam is expressed ubiquitously; however, the predominant domains of accumulation of mam RNA and protein during gastrulation are along the ventral longitudinal surface, including cells of the mesoderm, endoderm, mesectoderm, and neuroectoderm [9].
  • Previous studies have shown that during neurogenesis mam appears to be expressed throughout the ectoderm, mesoderm, and neuroblast layer of the germ band [9].

Associations of mam with chemical compounds

  • Interspecific sequence comparison of the highly repetitive Drosophila gene mastermind (mam) reveals extensive length variation in homopolymer domains [10].

Regulatory relationships of mam

  • Mam is ubiquitously expressed in wing and leg imaginal discs and is not down-regulated in sensory organ precursor cells of the wing margin or notum [7].

Other interactions of mam

  • Loss of function for mam, similar to loss of function for Notch, results in GMC-1 symmetrically dividing to generate two RP2 neurons [5].
  • Chromosome colocalization studies with RNA polymerase and the groucho corepressor protein implicate Mam in transcriptional regulation [7].
  • The vgU allele is associated with a chromosomal inversion which splits the vg locus, resulting in a gene fusion between vg and the mastermind (mam) neurogenic locus [11].
  • The locus contains a high density of repeated elements of two classes; opa (CAX)n and (dC-dA)n.(dG-dT)n. A preliminary study of the transcriptional activity of the mam region is presented [12].


  1. Mastermind acts downstream of notch to specify neuronal cell fates in the Drosophila central nervous system. Schuldt, A.J., Brand, A.H. Dev. Biol. (1999) [Pubmed]
  2. t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway. Tonon, G., Modi, S., Wu, L., Kubo, A., Coxon, A.B., Komiya, T., O'Neil, K., Stover, K., El-Naggar, A., Griffin, J.D., Kirsch, I.R., Kaye, F.J. Nat. Genet. (2003) [Pubmed]
  3. Transcriptional repression by suppressor of hairless involves the binding of a hairless-dCtBP complex in Drosophila. Morel, V., Lecourtois, M., Massiani, O., Maier, D., Preiss, A., Schweisguth, F. Curr. Biol. (2001) [Pubmed]
  4. Engineered truncations in the Drosophila mastermind protein disrupt Notch pathway function. Helms, W., Lee, H., Ammerman, M., Parks, A.L., Muskavitch, M.A., Yedvobnick, B. Dev. Biol. (1999) [Pubmed]
  5. Differential effects of Drosophila mastermind on asymmetric cell fate specification and neuroblast formation. Yedvobnick, B., Kumar, A., Chaudhury, P., Opraseuth, J., Mortimer, N., Bhat, K.M. Genetics (2004) [Pubmed]
  6. A human protein with sequence similarity to Drosophila mastermind coordinates the nuclear form of notch and a CSL protein to build a transcriptional activator complex on target promoters. Kitagawa, M., Oyama, T., Kawashima, T., Yedvobnick, B., Kumar, A., Matsuno, K., Harigaya, K. Mol. Cell. Biol. (2001) [Pubmed]
  7. The nuclear protein encoded by the Drosophila neurogenic gene mastermind is widely expressed and associates with specific chromosomal regions. Bettler, D., Pearson, S., Yedvobnick, B. Genetics (1996) [Pubmed]
  8. Identification of chromosomal deficiencies that modify Drosophila mastermind mutant phenotypes. Yedvobnick, B., Helms, W., Barrett, B. Genesis (2001) [Pubmed]
  9. Early ventral expression of the Drosophila neurogenic locus mastermind. Bettler, D., Schmid, A., Yedvobnick, B. Dev. Biol. (1991) [Pubmed]
  10. Drive-selection equilibrium: homopolymer evolution in the Drosophila gene mastermind. Newfeld, S.J., Tachida, H., Yedvobnick, B. J. Mol. Evol. (1994) [Pubmed]
  11. Genetic and molecular analysis of vgU and vgW: two dominant vg alleles associated with gene fusions in Drosophila. Williams, J.A., Scott, I.M., Atkin, A.L., Brook, W.J., Russell, M.A., Bell, J.B. Genetics (1990) [Pubmed]
  12. Molecular analysis of the neurogenic locus mastermind of Drosophila melanogaster. Yedvobnick, B., Smoller, D., Young, P., Mills, D. Genetics (1988) [Pubmed]
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