Amplification of neural stem cell proliferation by intermediate progenitor cells in Drosophila brain development
Tóm tắt
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. 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. 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.
Tài liệu tham khảo
Gotz M, Huttner WB: The cell biology of neurogenesis. Nat Rev Mol Cell Biol. 2005, 6 (10): 777-788. 10.1038/nrm1739.
Merkle FT, Alvarez-Buylla A: Neural stem cells in mammalian development. Curr Opin Cell Biol. 2006, 18 (6): 704-709. 10.1016/j.ceb.2006.09.008.
Kriegstein A, Noctor S, Martinez-Cerdeno V: Patterns of neural stem and progenitor cell division may underlie evolutionary cortical expansion. Nat Rev Neurosci. 2006, 7 (11): 883-890. 10.1038/nrn2008.
Morrison SJ, Kimble J: Asymmetric and symmetric stem-cell divisions in development and cancer. Nature. 2006, 441 (7097): 1068-1074. 10.1038/nature04956.
Al-Hajj M, Clarke MF: Self-renewal and solid tumor stem cells. Oncogene. 2004, 23 (43): 7274-7282. 10.1038/sj.onc.1207947.
Oliver TG, Wechsler-Reya RJ: Getting at the root and stem of brain tumors. Neuron. 2004, 42 (6): 885-888. 10.1016/j.neuron.2004.06.011.
Yu F, Kuo CT, Jan YN: Drosophila neuroblast asymmetric cell division: recent advances and implications for stem cell biology. Neuron. 2006, 51 (1): 13-20. 10.1016/j.neuron.2006.06.016.
Egger B, Chell JM, Brand AH: Insights into neural stem cell biology from flies. Philos Trans R Soc Lond B Biol Sci. 2008, 363 (1489): 39-59. 10.1098/rstb.2006.2011.
Karcavich RE: Generating neuronal diversity in the Drosophila central nervous system: a view from the ganglion mother cells. Dev Dyn. 2005, 232 (3): 609-616. 10.1002/dvdy.20273.
Skeath JB, Thor S: Genetic control of Drosophila nerve cord development. Curr Opin Neurobiol. 2003, 13 (1): 8-15. 10.1016/S0959-4388(03)00007-2.
Pearson BJ, Doe CQ: Specification of temporal identity in the developing nervous system. Annu Rev Cell Dev Biol. 2004, 20: 619-647. 10.1146/annurev.cellbio.19.111301.115142.
Technau GM, Berger C, Urbach R: Generation of cell diversity and segmental pattern in the embryonic central nervous system of Drosophila. Dev Dyn. 2006, 235 (4): 861-869. 10.1002/dvdy.20566.
Truman JW, Bate M: Spatial and temporal patterns of neurogenesis in the central nervous system of Drosophila melanogaster. Dev Biol. 1988, 125 (1): 145-157. 10.1016/0012-1606(88)90067-X.
Prokop A, Technau GM: The origin of postembryonic neuroblasts in the ventral nerve cord of Drosophila melanogaster. Development. 1991, 111 (1): 79-88.
Truman JW, Schuppe H, Shepherd D, Williams DW: Developmental architecture of adult-specific lineages in the ventral CNS of Drosophila. Development. 2004, 131 (20): 5167-5184. 10.1242/dev.01371.
Pereanu W, Hartenstein V: Neural lineages of the Drosophila brain: a three-dimensional digital atlas of the pattern of lineage location and projection at the late larval stage. J Neurosci. 2006, 26 (20): 5534-5553. 10.1523/JNEUROSCI.4708-05.2006.
Bardin AJ, Le Borgne R, Schweisguth F: Asymmetric localization and function of cell-fate determinants: a fly's view. Curr Opin Neurobiol. 2004, 14 (1): 6-14. 10.1016/j.conb.2003.12.002.
Betschinger J, Knoblich JA: Dare to be different: asymmetric cell division in Drosophila, C. elegans and vertebrates. Curr Biol. 2004, 14 (16): R674-85. 10.1016/j.cub.2004.08.017.
Wang H, Chia W: Drosophila neural progenitor polarity and asymmetric division. Biol Cell. 2005, 97 (1): 63-74. 10.1042/BC20040064.
Chu-Lagraff Q, Wright DM, McNeil LK, Doe CQ: The prospero gene encodes a divergent homeodomain protein that controls neuronal identity in Drosophila. Development. 1991, Suppl 2: 79-85.
Vaessin H, Grell E, Wolff E, Bier E, Jan LY, Jan YN: prospero is expressed in neuronal precursors and encodes a nuclear protein that is involved in the control of axonal outgrowth in Drosophila. Cell. 1991, 67 (5): 941-953. 10.1016/0092-8674(91)90367-8.
Li L, Vaessin H: Pan-neural Prospero terminates cell proliferation during Drosophila neurogenesis. Genes Dev. 2000, 14 (2): 147-151.
Choksi SP, Southall TD, Bossing T, Edoff K, de Wit E, Fischer BE, van Steensel B, Micklem G, Brand AH: Prospero acts as a binary switch between self-renewal and differentiation in Drosophila neural stem cells. Dev Cell. 2006, 11 (6): 775-789. 10.1016/j.devcel.2006.09.015.
Ikeshima-Kataoka H, Skeath JB, Nabeshima Y, Doe CQ, Matsuzaki F: Miranda directs Prospero to a daughter cell during Drosophila asymmetric divisions. Nature. 1997, 390 (6660): 625-629. 10.1038/37641.
Shen CP, Jan LY, Jan YN: Miranda is required for the asymmetric localization of Prospero during mitosis in Drosophila. Cell. 1997, 90 (3): 449-458. 10.1016/S0092-8674(00)80505-X.
Schuldt AJ, Adams JH, Davidson CM, Micklem DR, Haseloff J, St Johnston D, Brand AH: Miranda mediates asymmetric protein and RNA localization in the developing nervous system. Genes Dev. 1998, 12 (12): 1847-1857. 10.1101/gad.12.12.1847.
Knoblich JA, Jan LY, Jan YN: Asymmetric segregation of Numb and Prospero during cell division. Nature. 1995, 377 (6550): 624-627. 10.1038/377624a0.
Spana EP, Doe CQ: The prospero transcription factor is asymmetrically localized to the cell cortex during neuroblast mitosis in Drosophila. Development. 1995, 121 (10): 3187-3195.
Akong K, McCartney BM, Peifer M: Drosophila APC2 and APC1 have overlapping roles in the larval brain despite their distinct intracellular localizations. Dev Biol. 2002, 250 (1): 71-90. 10.1006/dbio.2002.0777.
Ceron J, Gonzalez C, Tejedor FJ: Patterns of cell division and expression of asymmetric cell fate determinants in postembryonic neuroblast lineages of Drosophila. Dev Biol. 2001, 230 (2): 125-138. 10.1006/dbio.2000.0110.
Bello B, Reichert H, Hirth F: The brain tumor gene negatively regulates neural progenitor cell proliferation in the larval central brain of Drosophila. Development. 2006, 133 (14): 2639-2648. 10.1242/dev.02429.
Betschinger J, Mechtler K, Knoblich JA: Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells. Cell. 2006, 124 (6): 1241-1253. 10.1016/j.cell.2006.01.038.
Lee CY, Wilkinson BD, Siegrist SE, Wharton RP, Doe CQ: Brat is a Miranda cargo protein that promotes neuronal differentiation and inhibits neuroblast self-renewal. Dev Cell. 2006, 10 (4): 441-449.
Maurange C, Gould AP: Brainy but not too brainy: starting and stopping neuroblast divisions in Drosophila. Trends Neurosci. 2005, 28 (1): 30-36. 10.1016/j.tins.2004.10.009.
Strausfeld: Atlas of an insect brain. 1976
Younossi-Hartenstein A, Nassif C, Green P, Hartenstein V: Early neurogenesis of the Drosophila brain. J Comp Neurol. 1996, 370 (3): 313-329. 10.1002/(SICI)1096-9861(19960701)370:3<313::AID-CNE3>3.0.CO;2-7.
Urbach R, Schnabel R, Technau GM: The pattern of neuroblast formation, mitotic domains and proneural gene expression during early brain development in Drosophila. Development. 2003, 130 (16): 3589-3606. 10.1242/dev.00528.
Ito K, Hotta Y: Proliferation pattern of postembryonic neuroblasts in the brain of Drosophila melanogaster. Dev Biol. 1992, 149 (1): 134-148. 10.1016/0012-1606(92)90270-Q.
Lee T, Luo L: Mosaic analysis with a repressible cell marker (MARCM) for Drosophila neural development. Trends Neurosci. 2001, 24 (5): 251-254. 10.1016/S0166-2236(00)01791-4.
Bello B, Holbro N, Reichert H: Polycomb group genes are required for neural stem cell survival in postembryonic neurogenesis of Drosophila. Development. 2007, 134 (6): 1091-1099. 10.1242/dev.02793.
Wu JS, Luo L: A protocol for mosaic analysis with a repressible cell marker (MARCM) in Drosophila. Nat Protoc. 2006, 1 (6): 2583-2589. 10.1038/nprot.2006.320.
Lee CY, Robinson KJ, Doe CQ: Lgl, Pins and aPKC regulate neuroblast self-renewal versus differentiation. Nature. 2006, 439 (7076): 594-598. 10.1038/nature04299.
Rusan NM, Peifer M: A role for a novel centrosome cycle in asymmetric cell division. J Cell Biol. 2007, 177 (1): 13-20. 10.1083/jcb.200612140.
Caussinus E, Gonzalez C: Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster. Nat Genet. 2005, 37 (10): 1125-1129. 10.1038/ng1632.
Haubensak W, Attardo A, Denk W, Huttner WB: Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: a major site of neurogenesis. Proc Natl Acad Sci U S A. 2004, 101 (9): 3196-3201. 10.1073/pnas.0308600100.
Noctor SC, Martinez-Cerdeno V, Ivic L, Kriegstein AR: Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat Neurosci. 2004, 7 (2): 136-144. 10.1038/nn1172.
Miyata T, Kawaguchi A, Saito K, Kawano M, Muto T, Ogawa M: Asymmetric production of surface-dividing and non-surface-dividing cortical progenitor cells. Development. 2004, 131 (13): 3133-3145. 10.1242/dev.01173.
Martinez-Cerdeno V, Noctor SC, Kriegstein AR: The role of intermediate progenitor cells in the evolutionary expansion of the cerebral cortex. Cereb Cortex. 2006, 16 Suppl 1: i152-61. 10.1093/cercor/bhk017.
ImageJ: A public domain Java image processing program . [http://rsb.info.nih.gov/ij]