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Notch Signaling and the Generation of Cell Diversity in Drosophila Neuroblast Lineages

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Notch Signaling in Embryology and Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 727))

Abstract

Notch is a membrane bound transcription factor and it plays fundamental roles in many cell-cell interaction events usually involving directly neighboring cells relating an extrinsic signal of a sending cell to the nucleus of the receiving cell to modulate gene expression patterns in this cell. Notch regulates cell fate specification, cell proliferation as well as cell death in the contexts of many organs and cell types. Although the mechanisms of signal transduction from the cell surface to the nucleus are relatively simple, it is not fully understood how such a straightforward pathway can result in tremendously complex outcomes at the cellular level. This chapter discusses some of the known roles of Notch during central nervous system development in Drosophila. In the CNS, Notch is a major player in creating cellular diversity on the level of binary cell fates by possibly activating differential gene expression in sibling cells arising through asymmetric cell division. This chapter also raises some questions related to Notch function during neural cell fate specification which have not yet been satisfactorily addressed in the field. Finding answers to these questions may provide further insights into how cell-cell interactions in the nervous system involving Notch control the generation of cellular diversity.

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References

  1. Azevedo FA, Carvalho LR, Grinberg LT et al. Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. J Comp Neurol 2009; 513(5):532–541.

    Article  PubMed  Google Scholar 

  2. Campos-Ortega JA. Cellular interactions during early neurogenesis of Drosophila melanogaster. Trends Neurosci 1988; 11(9):400–405.

    Article  PubMed  CAS  Google Scholar 

  3. Muskavitch MA. Delta-notch signaling and Drosophila cell fate choice. Dev Biol 1994; 166(2):415–430.

    Article  PubMed  CAS  Google Scholar 

  4. Campos-Ortega JA. Cellular interactions in the developing nervous system of Drosophila. Cell 1994; 77(7):969–975.

    Article  PubMed  CAS  Google Scholar 

  5. Fortini ME. Notch and presenilin: a proteolytic mechanism emerges. Curr Opin Cell Biol 2001; 13(5):627–634.

    Article  PubMed  CAS  Google Scholar 

  6. Kopan R. Notch: a membrane-bound transcription factor. J Cell Sci 2002; 115(Pt 6):1095–1097.

    PubMed  CAS  Google Scholar 

  7. Lecourtois M, Schweisguth F. The neurogenic suppressor of hairless DNA-binding protein mediates the transcriptional activation of the enhancer of split complex genes triggered by Notch signaling. Genes Dev 1995; 9(21):2598–2608.

    Article  PubMed  CAS  Google Scholar 

  8. Bossing T, Udolph G, Doe CQ et al. The embryonic central nervous system lineages of Drosophila melanogaster. I. Neuroblast lineages derived from the ventral half of the neuroectoderm. Dev Biol 1996; 179:41–64.

    Article  PubMed  CAS  Google Scholar 

  9. Schmid A, Chiba A, Doe CQ. Clonal analysis of Drosophila embryonic neuroblasts: neural cell types, axon projections and muscle targets. Development 1999; 126(21):4653–4689.

    PubMed  CAS  Google Scholar 

  10. Schmidt H, Rickert C, Bossing T et al. The embryonic central nervous system lineages of Drosophila melanogaster. II. Neuroblast lineages derived from the dorsal part of the neuroectoderm. Dev Biol 1997; 189:186–204.

    Article  PubMed  CAS  Google Scholar 

  11. Udolph G, Prokop A, Bossing T et al. Identification of a neuroglioblast in Drosophila and experimentell studies on its determination. Europ Dros Res Conf 13 1993:1A.

    Google Scholar 

  12. Jan YN, Jan LY. Polarity in cell division: what frames thy fearful asymmetry? Cell 2000; 100:599–602.

    Article  PubMed  CAS  Google Scholar 

  13. Kraut R, Campos-Ortega JA. Inscuteable, a neural precursor gene of Drosophila, encodes a candidate for a cytoskeleton adapter protein. Dev Biol 1996; 174:65–81.

    Article  PubMed  CAS  Google Scholar 

  14. Kraut R, Chia W, Jan LY et al. Role of inscuteable in orienting asymmetric cell division in Drosophila. Nature 1996; 383:50–55.

    Article  PubMed  CAS  Google Scholar 

  15. Schober M, Schaefer M, Knoblich JA. Bazooka recruits Inscuteable to orient asymmetric cell divisions in Drosophila neuroblasts. Nature 1999; 402(6761):548–551.

    Article  PubMed  CAS  Google Scholar 

  16. Wodarz A, Ramrath A, Grimm A et al. Drosophila atypical protein kinase C associates with Bazooka and controls polarity of epithelia and neuroblasts. J Cell Biol 2000; 150(6):1361–1374.

    Article  PubMed  CAS  Google Scholar 

  17. Petronczki M, Knoblich JA. DmPAR-6 directs epithelial polarity and asymmetric cell division of neuroblasts in Drosophila. Nat Cell Biol 2001; 3(1):43–49.

    Article  PubMed  CAS  Google Scholar 

  18. Yu F, Cai Y, Kaushik R et al. Distinct roles of Galphai and Gbeta13F subunits of the heterotrimeric G protein complex in the mediation of Drosophila neuroblast asymmetric divisions. J Cell Biol 2003; 162(4):623–633.

    Article  PubMed  CAS  Google Scholar 

  19. Parmentier ML, Woods D, Greig S et al. Rapsynoid/partner of inscuteable controls asymmetric division of larval neuroblasts in Drosophila. J Neurosci (Online) 2000; 20:RC84(81–85).

    Google Scholar 

  20. Schaefer M, Shevchenko A, Knoblich JA. A protein complex containing Inscuteable and the Galpha-binding protein Pins orients asymmetric cell divisions in Drosophila. Curr Biol 2000; 10(7):353–362.

    Article  PubMed  CAS  Google Scholar 

  21. Yu F, Morin X, Cai Y et al. Analysis of partner of inscuteable, a novel player of Drosophila asymmetric divisions, reveals two distinct steps in inscuteable apical localization. Cell 2000; 100(4):399–409.

    Article  PubMed  CAS  Google Scholar 

  22. Yu F, Wang H, Qian H et al. Locomotion defects, together with Pins, regulates heterotrimeric G-protein signaling during Drosophila neuroblast asymmetric divisions. Genes Dev 2005; 19(11):1341–1353.

    Article  PubMed  CAS  Google Scholar 

  23. Siller KH, Doe CQ. Spindle orientation during asymmetric cell division. Nat Cell Biol 2009; 11(4):365–374.

    Article  PubMed  CAS  Google Scholar 

  24. Wodarz A. Molecular control of cell polarity and asymmetric cell division in Drosophila neuroblasts. Curr Opin Cell Biol 2005; 17(5):475–481.

    Article  PubMed  CAS  Google Scholar 

  25. Spana EP, Doe CQ. Numb antagonizes Notch signaling to specify sibling neuron cell fates. Neuron 1996; 17(1):21–26.

    Article  PubMed  CAS  Google Scholar 

  26. Buescher M, Yeo SL, Udolph G et al. Binary sibling neuronal cell fate decisions in the Drosophila embryonic central nervous system are nonstochastic and require inscuteable-mediated asymmetry of ganglion mother cells. Genes Dev 1998; 12(12):1858–1870.

    Article  PubMed  CAS  Google Scholar 

  27. Skeath JB, Doe CQ. Sanpodo and Notch act in opposition to Numb to distinguish sibling neuron fates in the Drosophila CNS. Development 1998; 125(10):1857–1865.

    PubMed  CAS  Google Scholar 

  28. Udolph G, Rath P, Chia W. A requirement for Notch in the genesis of a subset of glial cells in the Drosophila embryonic central nervous system which arise through asymmetric divisions. Development 2001; 128(8):1457–1466.

    PubMed  CAS  Google Scholar 

  29. Van De Bor V, Giangrande A. Notch signaling represses the glial fate in fly PNS. Development 2001; 128(8):1381–1390.

    Google Scholar 

  30. Umesono Y, Hiromi Y, Hotta Y. Context-dependent utilization of Notch activity in Drosophila glial determination. Development 2002; 129(10):2391–2399.

    PubMed  CAS  Google Scholar 

  31. Udolph G, Rath P, Tio M et al. On the roles of Notch, Delta, kuzbanian and inscuteable during the development of Drosophila embryonic neuroblast lineages. Dev Biol 2009; 336(2):156-168.

    Google Scholar 

  32. Rath P, Lin S, Udolph G et al. Inscuteable-independent apicobasally oriented asymmetric divisions in the Drosophila embryonic CNS. EMBO Rep 2002; 3(7):660–665.

    Article  PubMed  CAS  Google Scholar 

  33. Almeida MS, Bray SJ. Regulation of post-embryonic neuroblasts by Drosophila Grainyhead. Mech Dev 2005; 122(12):1282–1293.

    Article  PubMed  CAS  Google Scholar 

  34. Novotny T, Eiselt R, Urban J. Hunchback is required for the specification of the early sublineage of neuroblast 7-3 in the Drosophila central nervous system. Development 2002; 129(4):1027–1036.

    PubMed  CAS  Google Scholar 

  35. Lundell MJ, Lee HK, Perez E et al. The regulation of apoptosis by Numb/Notch signaling in the serotonin lineage of Drosophila. Development 2003; 130(17):4109–4121.

    Article  PubMed  CAS  Google Scholar 

  36. Lee HK, Lundell MJ. Differentiation of the Drosophila serotonergic lineage depends on the regulation of Zfh-1 by Notch and Eagle. Mol Cell Neurosci 2007; 36(1):47–58.

    Article  PubMed  CAS  Google Scholar 

  37. Truman JW, Moats W, Altman J et al. Role of Notch signaling in establishing the hemilineages of secondary neurons in Drosophila melanogaster. Development 2010; 137(1):53–61.

    Article  PubMed  CAS  Google Scholar 

  38. Kambadur R, Koizumi K, Stivers C et al. Regulation of POU genes by castor and hunchback establishes layered compartments in the Drosophila CNS. Genes Dev 1998; 12(2):246-260.

    Google Scholar 

  39. Isshiki T, Pearson B, Holbrook S et al. Drosophila neuroblasts sequentially express transcription factors which specify the temporal identity of their neuronal progeny. Cell 2001; 106(4):511–521.

    Article  PubMed  CAS  Google Scholar 

  40. Pearson BJ, Doe CQ. Regulation of neuroblast competence in Drosophila. Nature 2003; 425(6958):624–628.

    Article  PubMed  CAS  Google Scholar 

  41. Mettler U, Vogler G, Urban J. Timing of identity: spatiotemporal regulation of hunchback in neuroblast lineages of Drosophila by Seven-up and Prospero. Development 2006; 133(3):429–437.

    Article  PubMed  CAS  Google Scholar 

  42. Yang X, Bahri S, Klein T et al. Klumpfuss, a putative Drosophila zinc finger transcription factor, acts to differentiate between the identities of two secondary precursor cells within one neuroblast lineage. Genes Dev 1997; 11(11):1396–1408.

    Article  PubMed  CAS  Google Scholar 

  43. Koelzer S, Klein T. A Notch-independent function of Suppressor of Hairless during the development of the bristle sensory organ precursor cell of Drosophila. Development 2003; 130(9):1973–1988.

    Article  PubMed  CAS  Google Scholar 

  44. Monastirioti M, Giagtzoglou N, Koumbanakis KA et al. Drosophila Hey is a target of Notch in asymmetric divisions during embryonic and larval neurogenesis. Development 2010; 137(2):191–201.

    Article  PubMed  CAS  Google Scholar 

  45. Krejci A, Bernard F, Housden BE et al. Direct response to Notch activation: signaling crosstalk and incoherent logic. Sci Signal 2009; 2(55):ra1.

    Article  Google Scholar 

  46. Kurooka H, Honjo T. Functional interaction between the mouse notch1 intracellular region and histone acetyltransferases PCAF and GCN5. J Biol Chem 2000; 275(22):17211–17220.

    Article  PubMed  CAS  Google Scholar 

  47. Armstrong JA, Sperling AS, Deuring R et al. Genetic screens for enhancers of brahma reveal functional interactions between the BRM chromatin-remodeling complex and the delta-notch signal transduction pathway in Drosophila. Genetics 2005; 170(4):1761–1774.

    Article  PubMed  CAS  Google Scholar 

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Udolph, G. (2012). Notch Signaling and the Generation of Cell Diversity in Drosophila Neuroblast Lineages. In: Reichrath, J., Reichrath, S. (eds) Notch Signaling in Embryology and Cancer. Advances in Experimental Medicine and Biology, vol 727. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0899-4_4

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