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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Gene Review

pros  -  prospero

Drosophila melanogaster

Synonyms: 0244/09, 0320/10, 0441/16, 0451/09, 0563/18, ...
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Disease relevance of pros


Psychiatry related information on pros

  • The position of such QTL (approximately 84A-88B) with effects on courtship and copulation aspects of mating includes the candidate sex determination gene doublesex (84E5-6) and Voila (86E1-2), a gene that affects male courtship in D. melanogaster [3].

High impact information on pros

  • Like Prospero, Brat binds and cosegregates with the adaptor protein Miranda [1].
  • Similar defects are seen in lethal giant larvae (lgl) mutants where Brat and Prospero are not asymmetric [1].
  • While Prospero regulates cell-cycle gene transcription, Brat acts as a posttranscriptional inhibitor of dMyc [1].
  • A direct link is established between DER activation of a transcription enhancer in prospero and binding of two transcription factors that are targets of DER signaling [4].
  • We show that Sevenless activates prospero independent of the enhancer and involves targeted degradation of Tramtrack, a transcription repressor [4].

Biological context of pros


Anatomical context of pros


Associations of pros with chemical compounds

  • Our data suggest that DTRAF1 binds to Baz and acts downstream of Egr in the Mira/Pros telophase rescue pathway [7].
  • This compensatory mechanism has been referred to as 'telophase rescue'. We demonstrate that the Drosophila homolog of the mammalian tumor-necrosis factor (TNF) receptor-associated factor (DTRAF1) and Eiger (Egr), the homolog of the mammalian TNF, are required for telophase rescue of Mira/Pros [7].
  • Regulated transcription of the prospero gene in the Drosophila eye provides a model for how gene expression is specifically controlled by signals from receptor tyrosine kinases [4].
  • Nuclear export of Prospero, which is sensitive to the drug leptomycin B, is mediated by Exportin [13].

Physical interactions of pros


Enzymatic interactions of pros

  • Hyperstable Yan (ACT) cannot be phosphorylated and blocks prospero expression [14].

Regulatory relationships of pros

  • In Drosophila neuroblasts, inscuteable controls both spindle orientation and the asymmetric localization of the cell-fate determinants Prospero and Numb [15].
  • Furthermore, the maintenance of hb expression in the GMC is regulated by the activity of Prospero (Pros), a transcription factor which asymmetrically segregates into the GMC during mitosis and inhibits Svp activity on both, the transcriptional and posttranscriptional level [16].
  • Neuronal Vein activates the MAPKinase signalling pathway in the glia with highest Prospero levels, coupling axon extension with glial proliferation [10].
  • The expression of Pros in the normal PIIb cell appears to be regulated by Notch signaling [17].
  • Dendrite development is altered in prospero mutants and in transgenic embryos expressing a constitutively active form of the small GTPase cdc42 [18].

Other interactions of pros

  • Thus, the differential regulation of hb between the neuroblasts and the ganglion mother cells is achieved by a mechanism that integrates information created by the asymmetric distribution of a cell-fate determinant upon mitosis (Prospero) and a transcriptional repressor present in both cells (Seven-up) [2].
  • In this study, we show that Miranda is colocalized with Staufen and Prospero in neuroblasts, and is required for the asymmetric cortical localization of both proteins [19].
  • Simultaneous expression of inscuteable and string in the snail family deletion mutant efficiently restores Prospero expression in ganglion mother cells, demonstrating that the two genes are key targets of Snail in neuroblasts [20].
  • First, we found that prospero (pros) mutations led to a loss of expression of Glial cells missing, which is essential to trigger glial differentiation, in the NB6-4T lineage [11].
  • However, from stage 15 of embryogenesis, expression of locomotion defects (loco) and prospero (pros) was found to be missing in a subset of LG [21].

Analytical, diagnostic and therapeutic context of pros


  1. Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells. Betschinger, J., Mechtler, K., Knoblich, J.A. Cell (2006) [Pubmed]
  2. Timing of identity: spatiotemporal regulation of hunchback in neuroblast lineages of Drosophila by Seven-up and Prospero. Mettler, U., Vogler, G., Urban, J. Development (2006) [Pubmed]
  3. The genetics of mating recognition between Drosophila simulans and D. sechellia. Civetta, A., Cantor, E.J. Genet. Res. (2003) [Pubmed]
  4. Overlapping activators and repressors delimit transcriptional response to receptor tyrosine kinase signals in the Drosophila eye. Xu, C., Kauffmann, R.C., Zhang, J., Kladny, S., Carthew, R.W. Cell (2000) [Pubmed]
  5. Inscuteable and Staufen mediate asymmetric localization and segregation of prospero RNA during Drosophila neuroblast cell divisions. Li, P., Yang, X., Wasser, M., Cai, Y., Chia, W. Cell (1997) [Pubmed]
  6. 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]
  7. Drosophila homologs of mammalian TNF/TNFR-related molecules regulate segregation of Miranda/Prospero in neuroblasts. Wang, H., Cai, Y., Chia, W., Yang, X. EMBO J. (2006) [Pubmed]
  8. Miranda mediates asymmetric protein and RNA localization in the developing nervous system. Schuldt, A.J., Adams, J.H., Davidson, C.M., Micklem, D.R., Haseloff, J., St Johnston, D., Brand, A.H. Genes Dev. (1998) [Pubmed]
  9. 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]
  10. Prospero maintains the mitotic potential of glial precursors enabling them to respond to neurons. Griffiths, R.L., Hidalgo, A. EMBO J. (2004) [Pubmed]
  11. Mechanism of glia-neuron cell-fate switch in the Drosophila thoracic neuroblast 6-4 lineage. Akiyama-Oda, Y., Hotta, Y., Tsukita, S., Oda, H. Development (2000) [Pubmed]
  12. Role of inscuteable in orienting asymmetric cell divisions in Drosophila. Kraut, R., Chia, W., Jan, L.Y., Jan, Y.N., Knoblich, J.A. Nature (1996) [Pubmed]
  13. Regulated nuclear export of the homeodomain transcription factor Prospero. Demidenko, Z., Badenhorst, P., Jones, T., Bi, X., Mortin, M.A. Development (2001) [Pubmed]
  14. Yan regulates Lozenge during Drosophila eye development. Behan, K.J., Nichols, C.D., Cheung, T.L., Farlow, A., Hogan, B.M., Batterham, P., Pollock, J.A. Dev. Genes Evol. (2002) [Pubmed]
  15. Bazooka provides an apical cue for Inscuteable localization in Drosophila neuroblasts. Wodarz, A., Ramrath, A., Kuchinke, U., Knust, E. Nature (1999) [Pubmed]
  16. Connecting temporal identity to mitosis: the regulation of Hunchback in Drosophila neuroblast lineages. Urban, J., Mettler, U. Cell Cycle (2006) [Pubmed]
  17. Sibling cell fate in the Drosophila adult external sense organ lineage is specified by prospero function, which is regulated by Numb and Notch. Reddy, G.V., Rodrigues, V. Development (1999) [Pubmed]
  18. Genes regulating dendritic outgrowth, branching, and routing in Drosophila. Gao, F.B., Brenman, J.E., Jan, L.Y., Jan, Y.N. Genes Dev. (1999) [Pubmed]
  19. Identification of Miranda protein domains regulating asymmetric cortical localization, cargo binding, and cortical release. Fuerstenberg, S., Peng, C.Y., Alvarez-Ortiz, P., Hor, T., Doe, C.Q. Mol. Cell. Neurosci. (1998) [Pubmed]
  20. The Snail protein family regulates neuroblast expression of inscuteable and string, genes involved in asymmetry and cell division in Drosophila. Ashraf, S.I., Ip, Y.T. Development (2001) [Pubmed]
  21. The dead ringer/retained transcriptional regulatory gene is required for positioning of the longitudinal glia in the Drosophila embryonic CNS. Shandala, T., Takizawa, K., Saint, R. Development (2003) [Pubmed]
  22. Biochemical analysis of ++Prospero protein during asymmetric cell division: cortical Prospero is highly phosphorylated relative to nuclear Prospero. Srinivasan, S., Peng, C.Y., Nair, S., Skeath, J.B., Spana, E.P., Doe, C.Q. Dev. Biol. (1998) [Pubmed]
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