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Gene Review

numb  -  CG3779 gene product from transcript CG3779-RB

Drosophila melanogaster

Synonyms: CG3779, Dmel\CG3779, N7-1, Nb, Numb, ...
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Disease relevance of numb

  • Similarly asymmetric localisation and segregation of the determinant Numb during ganglion mother cell divisions ensure that the progeny sibling neurons attain distinct fates [1].

High impact information on numb

  • Here, we describe a Numb- and Neuralized-independent mechanism that acts redundantly in cell-fate specification [2].
  • Loss of pon function disrupts Numb localization in muscle progenitors and delays Numb crescent formation in neural precursors [3].
  • Partner of Numb colocalizes with Numb during mitosis and directs Numb asymmetric localization in Drosophila neural and muscle progenitors [3].
  • Moreover, ectopically expressed PON responds to the apical-basal polarity of epithelial cells and is sufficient to localize Numb basally [3].
  • Asymmetric division of Drosophila neuroblasts, sensory organ precursor cells, and cells in the procephalic neurogenic region involves the segregation of Numb and Prospero proteins into one of the two daughter cells [4].

Biological context of numb

  • Neuroblasts in the developing Drosophila CNS asymmetrically localize the cell fate determinants Numb and Prospero as well as prospero RNA to the basal cortex during mitosis [5].
  • During asymmetric cell division, the membrane-associated Numb protein localizes to a crescent in the mitotic progenitor and is segregated predominantly to one of the two daughter cells [6].
  • Overexpression of Nak in the sensory organs causes both daughters of a normally asymmetric cell division to adopt the same cell fate, a transformation similar to the loss of numb function phenotype and opposite the cell fate transformation caused by overexpression of Numb [6].
  • The frequency of cell fate transformation is sensitive to the numb gene dosage, as expected from the physical interaction between Nak and Numb [6].
  • We show here that Numb acts in SOP cells by inducing the endocytosis of Sanpodo, a four-pass transmembrane protein that has previously been shown to regulate Notch signalling in the central nervous system [7].

Anatomical context of numb

  • Thus, Lgl regulates cell fate by controlling Pon cortical localization, asymmetric localization of Numb and Neuralized, and plasma-membrane localization of Sandopo [8].
  • In pins mutants, these epithelial cells were not affected, but neuroblasts showed defects in the orientation of their mitotic spindle and the basal asymmetric localisation of Numb and Miranda during metaphase [9].
  • The adaptor protein Numb is necessary for the cell fate specification of progenitor cells in the Drosophila nervous system [10].
  • Neuroblasts that delaminate from the embryonic epithelium require lgl to promote formation of a basal Numb and Prospero crescent, which will be asymmetrically segregated to the basal daughter cell upon division to specify cell fate [11].
  • In contrast to centrosome positioning, however, Numb and Prospero localization is independent of microtubules [12].

Associations of numb with chemical compounds


Physical interactions of numb

  • In the NB4-2->GMC-1->RP2/sib lineage, one of the well-studied neuronal lineages in the ventral nerve cord, the Notch (N) signaling interacts with the asymmetrically localized Numb (Nb) to specify sibling neuronal fates to daughter cells of GMC-1 [16].
  • Mutant forms of alpha-Adaptin that no longer bind to Numb fail to localize asymmetrically and cause numb-like defects in asymmetric cell division [17].
  • Two independent amino acid changes that interfere with Shc binding to phosphotyrosine residues do not affect Numb activity in vivo [18].

Co-localisations of numb


Regulatory relationships of numb

  • Our results indicate that when Numb inhibits Notch signaling, cells undergo neuronal differentiation, whereas cells that maintain Notch signaling initiate apoptosis [15].

Other interactions of numb

  • Our data suggest that AurA, aPKC, Numb, and Notch function in a pathway that involved a series of negative genetic interactions [19].
  • We found that the Numb PTB domain but not the Shc PTB domain interacts with Nak through a peptide of 11 amino acids, implicating a novel and specific protein-protein interaction [6].
  • In the absence of nb, cells follow the same fate as they would in the presence of a gain-of-function N allele, such as Ax [20].
  • The correct positioning of Numb and the proper orientation of division require Inscuteable (Insc) [21].
  • This leads to Ttk expression in the daughter cell that does not inherit Numb [22].

Analytical, diagnostic and therapeutic context of numb


  1. A functional analysis of inscuteable and its roles during Drosophila asymmetric cell divisions. Tio, M., Zavortink, M., Yang, X., Chia, W. J. Cell. Sci. (1999) [Pubmed]
  2. Asymmetric Rab 11 endosomes regulate delta recycling and specify cell fate in the Drosophila nervous system. Emery, G., Hutterer, A., Berdnik, D., Mayer, B., Wirtz-Peitz, F., Gaitan, M.G., Knoblich, J.A. Cell (2005) [Pubmed]
  3. Partner of Numb colocalizes with Numb during mitosis and directs Numb asymmetric localization in Drosophila neural and muscle progenitors. Lu, B., Rothenberg, M., Jan, L.Y., Jan, Y.N. Cell (1998) [Pubmed]
  4. Miranda is required for the asymmetric localization of Prospero during mitosis in Drosophila. Shen, C.P., Jan, L.Y., Jan, Y.N. Cell (1997) [Pubmed]
  5. Miranda as a multidomain adapter linking apically localized Inscuteable and basally localized Staufen and Prospero during asymmetric cell division in Drosophila. Shen, C.P., Knoblich, J.A., Chan, Y.M., Jiang, M.M., Jan, L.Y., Jan, Y.N. Genes Dev. (1998) [Pubmed]
  6. Numb-associated kinase interacts with the phosphotyrosine binding domain of Numb and antagonizes the function of Numb in vivo. Chien, C.T., Wang, S., Rothenberg, M., Jan, L.Y., Jan, Y.N. Mol. Cell. Biol. (1998) [Pubmed]
  7. Numb and alpha-Adaptin regulate Sanpodo endocytosis to specify cell fate in Drosophila external sensory organs. Hutterer, A., Knoblich, J.A. EMBO Rep. (2005) [Pubmed]
  8. Lethal giant larvae controls the localization of notch-signaling regulators numb, neuralized, and Sanpodo in Drosophila sensory-organ precursor cells. Langevin, J., Le Borgne, R., Rosenfeld, F., Gho, M., Schweisguth, F., Bellaïche, Y. Curr. Biol. (2005) [Pubmed]
  9. A protein complex containing Inscuteable and the Galpha-binding protein Pins orients asymmetric cell divisions in Drosophila. Schaefer, M., Shevchenko, A., Shevchenko, A., Knoblich, J.A. Curr. Biol. (2000) [Pubmed]
  10. The cell fate determinant numb interacts with EHD/Rme-1 family proteins and has a role in endocytic recycling. Smith, C.A., Dho, S.E., Donaldson, J., Tepass, U., McGlade, C.J. Mol. Biol. Cell (2004) [Pubmed]
  11. Lethal giant larvae acts together with numb in notch inhibition and cell fate specification in the Drosophila adult sensory organ precursor lineage. Justice, N., Roegiers, F., Jan, L.Y., Jan, Y.N. Curr. Biol. (2003) [Pubmed]
  12. Asymmetric segregation of Numb and Prospero during cell division. Knoblich, J.A., Jan, L.Y., Jan, Y.N. Nature (1995) [Pubmed]
  13. Bazooka is required for localization of determinants and controlling proliferation in the sensory organ precursor cell lineage in Drosophila. Roegiers, F., Younger-Shepherd, S., Jan, L.Y., Jan, Y.N. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  14. High-affinity binding of the Drosophila Numb phosphotyrosine-binding domain to peptides containing a Gly-Pro-(p)Tyr motif. Li, S.C., Songyang, Z., Vincent, S.J., Zwahlen, C., Wiley, S., Cantley, L., Kay, L.E., Forman-Kay, J., Pawson, T. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  15. The regulation of apoptosis by Numb/Notch signaling in the serotonin lineage of Drosophila. Lundell, M.J., Lee, H.K., Pérez, E., Chadwell, L. Development (2003) [Pubmed]
  16. Cell division genes promote asymmetric interaction between Numb and Notch in the Drosophila CNS. Wai, P., Truong, B., Bhat, K.M. Development (1999) [Pubmed]
  17. The endocytic protein alpha-Adaptin is required for numb-mediated asymmetric cell division in Drosophila. Berdnik, D., Török, T., González-Gaitán, M., Knoblich, J.A. Dev. Cell (2002) [Pubmed]
  18. Functional analysis of the Numb phosphotyrosine-binding domain using site-directed mutagenesis. Yaich, L., Ooi, J., Park, M., Borg, J.P., Landry, C., Bodmer, R., Margolis, B. J. Biol. Chem. (1998) [Pubmed]
  19. Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts. Wang, H., Somers, G.W., Bashirullah, A., Heberlein, U., Yu, F., Chia, W. Genes Dev. (2006) [Pubmed]
  20. Numb suppresses the negative complementation at the Notch locus of Drosophila melanogaster, suggesting a putative mechanism for negative complementation. Portin, P. Genet. Res. (2001) [Pubmed]
  21. Binary sibling neuronal cell fate decisions in the Drosophila embryonic central nervous system are nonstochastic and require inscuteable-mediated asymmetry of ganglion mother cells. Buescher, M., Yeo, S.L., Udolph, G., Zavortink, M., Yang, X., Tear, G., Chia, W. Genes Dev. (1998) [Pubmed]
  22. Control of daughter cell fates during asymmetric division: interaction of Numb and Notch. Guo, M., Jan, L.Y., Jan, Y.N. Neuron (1996) [Pubmed]
  23. Only a subset of the binary cell fate decisions mediated by Numb/Notch signaling in Drosophila sensory organ lineage requires Suppressor of Hairless. Wang, S., Younger-Shepherd, S., Jan, L.Y., Jan, Y.N. Development (1997) [Pubmed]
  24. Asymmetric segregation of Numb in retinal development and the influence of the pigmented epithelium. Cayouette, M., Whitmore, A.V., Jeffery, G., Raff, M. J. Neurosci. (2001) [Pubmed]
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