Amplification of neural stem cell proliferation by intermediate progenitor cells in Drosophila brain development

被引:273
作者
Bello, Bruno C. [1 ]
Izergina, Natalya [1 ]
Caussinus, Emmanuel [1 ]
Reichert, Heinrich [1 ]
机构
[1] Univ Basel, Biozentrum, CH-4056 Basel, Switzerland
关键词
D O I
10.1186/1749-8104-3-5
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: In the mammalian brain, neural stem cells divide asymmetrically and often amplify the number of progeny they generate via symmetrically dividing intermediate progenitors. Here we investigate whether specific neural stem cell-like neuroblasts in the brain of Drosophila might also amplify neuronal proliferation by generating symmetrically dividing intermediate progenitors. Results: Cell lineage-tracing and genetic marker analysis show that remarkably large neuroblast lineages exist in the dorsomedial larval brain of Drosophila. These lineages are generated by brain neuroblasts that divide asymmetrically to self renew but, unlike other brain neuroblasts, do not segregate the differentiating cell fate determinant Prospero to their smaller daughter cells. These daughter cells continue to express neuroblast-specific molecular markers and divide repeatedly to produce neural progeny, demonstrating that they are proliferating intermediate progenitors. The proliferative divisions of these intermediate progenitors have novel cellular and molecular features; they are morphologically symmetrical, but molecularly asymmetrical in that key differentiating cell fate determinants are segregated into only one of the two daughter cells. Conclusion: Our findings provide cellular and molecular evidence for a new mode of neurogenesis in the larval brain of Drosophila that involves the amplification of neuroblast proliferation through intermediate progenitors. This type of neurogenesis bears remarkable similarities to neurogenesis in the mammalian brain, where neural stem cells as primary progenitors amplify the number of progeny they generate through generation of secondary progenitors. This suggests that key aspects of neural stem cell biology might be conserved in brain development of insects and mammals.
引用
收藏
页数:17
相关论文
共 50 条
  • [1] Drosophila APC2 and APC1 have overlapping roles in the larval brain despite their distinct intracellular localizations
    Akong, K
    McCartney, BM
    Peifer, M
    [J]. DEVELOPMENTAL BIOLOGY, 2002, 250 (01) : 71 - 90
  • [2] Self-renewal and solid tumor stem cells
    Al-Hajj, M
    Clarke, MF
    [J]. ONCOGENE, 2004, 23 (43) : 7274 - 7282
  • [3] Asymmetric localization and function of cell-fate determinants: a fly's view
    Bardin, AJ
    Le Borgne, R
    Schweisguth, F
    [J]. CURRENT OPINION IN NEUROBIOLOGY, 2004, 14 (01) : 6 - 14
  • [4] The brain tumor gene negatively regulates neural progenitor cell proliferation in the larval central brain of Drosophila
    Bello, Bruno
    Reichert, Heinrich
    Hirth, Frank
    [J]. DEVELOPMENT, 2006, 133 (14): : 2639 - 2648
  • [5] Polycomb group genes are required for neural stem cell survival in postembryonic neurogenesis of Drosophila
    Bello, Bruno
    Holbro, Niklaus
    Reichert, Heinrich
    [J]. DEVELOPMENT, 2007, 134 (06): : 1091 - 1099
  • [6] Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells
    Betschinger, J
    Mechtler, K
    Knoblich, JA
    [J]. CELL, 2006, 124 (06) : 1241 - 1253
  • [7] Dare to be different:: Asymmetric cell division in Drosophila, C-elegans and vertebrates
    Betschinger, J
    Knoblich, JA
    [J]. CURRENT BIOLOGY, 2004, 14 (16) : R674 - R685
  • [8] Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster
    Caussinus, E
    Gonzalez, C
    [J]. NATURE GENETICS, 2005, 37 (10) : 1125 - 1129
  • [9] Patterns of cell division and expression of asymmetric cell fate determinants in postembryonic neuroblast lineages of Drosophila
    Ceron, J
    González, C
    Tejedor, FJ
    [J]. DEVELOPMENTAL BIOLOGY, 2001, 230 (02) : 125 - 138
  • [10] Prospero acts as a binary switch between self-renewal and differentiation in Drosophila neural stem cells
    Choksi, Semil P.
    Southall, Tony D.
    Bossing, Torsten
    Edoff, Karin
    de Wit, Elzo
    Fischer, Bettina E.
    van Steensel, Bas
    Micklem, Gos
    Brand, Andrea H.
    [J]. DEVELOPMENTAL CELL, 2006, 11 (06) : 775 - 789