The cerebral cortex is built up of numerous neurons and cells supporting them, most of which originate from neural stem cells (NSCs). NSCs divide symmetrically to produce themselves and asymmetrically to generate neurons, and both types of divisions reply on faithful segregation of chromosomes into daughter cells. In the current study, we study the functions of evolutionarily conserved chromosome regulators, known as condensin I and condensin II, during development of the cerebral cortex in mice. We find that condensins I and II have both overlapping and non-overlapping functions in NSC divisions and survival: loss of either one of condensins causes distinct abnormalities in the process of chromosome segregation. Remarkably, loss of condensin II, but not of condensin I, also alters chromosome architecture during non-dividing stages. Our results demonstrate convincingly that an intricate balance between condensins I and II plays a crucial role in NSC divisions. It will be of great interest to test in the future whether such balancing acts of the two condensin complexes might be misregulated in tumorigenic NSCs that undergo uncontrolled cell divisions.
Vyšlo v časopise: Overlapping and Non-overlapping Functions of Condensins I and II in Neural Stem Cell Divisions. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004847 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004847
1. KriegsteinA, Alvarez-BuyllaA (2009) The glial nature of embryonic and adult neural stem cells. Annu Rev Neurosci 32 : 149–184.
2. ParidaenJTML, HuttnerWB (2014) Neurogenesis during development of the vertebrate central nervous system. EMBO Rep 15 : 351–364.
3. BushmanD, ChunJ (2013) The genomically mosaic brain: aneuploidy and more in neural diversity and disease. Semin Cell Dev Biol 24 : 357–369.
4. HiranoT (2012) Condensins: universal organizers of chromosomes with diverse functions. Genes Dev 26 : 1659–1678.
5. FujiwaraT, TanakaK, KuroiwaT, HiranoT (2013) Spatiotemporal dynamics of condensins I and II: evolutionary insights from the primitive red alga Cyanidioschyzon merolae. Mol Biol Cell 24 : 2515–2527.
6. HartlTA, SweeneySJ, KneplerPJ, BoscoG (2008) Condensin II resolves chromosomal associations to enable anaphase I segregation in Drosophila male meiosis. PLoS Genet 4: e1000228.
7. HartlTA, SmithHF, BoscoG (2008) Chromosome alignment and transvection are antagonized by condensin II. Science 322 : 1384–1387.
8. SakamotoT, InuiYT, UraguchiS, YoshizumiT, MatsunagaS, et al. (2011) Condensin II alleviates DNA damage and is essential for tolerance of boron overload stress in Arabidopsis. Plant Cell 23 : 3533–3546.
9. ShintomiK, HiranoT (2011) The relative ratio of condensin I to II determines chromosome shapes. Genes Dev 25 : 1464–1469.
10. ThorntonGK, WoodsCG (2009) Primary microcephaly: do all roads lead to Rome? Trends Genet 25 : 501–510.
11. YamashitaD, ShintomiK, OnoT, GavvovidisI, SchindlerD, et al. (2011) MCPH1 regulates chromosome condensation and shaping as a composite modulator of condensin II. J Cell Biol 194 : 841–854.
12. CsankovszkiG, ColletteK, SpahlK, CareyJ, SnyderM, et al. (2009) Three distinct condensin complexes control C. elegans chromosome dynamics. Curr Biol 19 : 9–19.
13. OnoT, LosadaA, HiranoM, MyersMP, NeuwaldAF, et al. (2003) Differential contributions of condensin I and condensin II to mitotic chromosome architecture in vertebrate cells. Cell 115 : 109–121.
14. HirotaT, GerlichD, KochB, EllenbergJ, PetersJ-M (2004) Distinct functions of condensin I and II in mitotic chromosome assembly. J Cell Sci 117 : 6435–6445.
15. GreenLC, KalitsisP, ChangTM, CipeticM, KimJH, et al. (2012) Contrasting roles of condensin I and condensin II in mitotic chromosome formation. J Cell Sci 125 : 1591–1604.
16. OnoT, FangY (2004) Spatial and temporal regulation of Condensins I and II in mitotic chromosome assembly in human cells. Mol Biol Cell 15 : 3296–3308.
17. LeeJ, OgushiS, SaitouM, HiranoT (2011) Condensins I and II are essential for construction of bivalent chromosomes in mouse oocytes. Mol Biol Cell 22 : 3465–3477.
18. TroncheF, KellendonkC, KretzO, GassP, AnlagK, et al. (1999) Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nat Genet 23 : 99–103.
19. HevnerRF, DazaRAM, RubensteinJLR, StunnenbergH, OlavarriaJF, et al. (2003) Beyond laminar fate: toward a molecular classification of cortical projection/pyramidal neurons. Dev Neurosci 25 : 139–151.
20. KawauchiT, ShikanaiM, KosodoY (2013) Extra-cell cycle regulatory functions of cyclin-dependent kinases (CDK) and CDK inhibitor proteins contribute to brain development and neurological disorders. Genes to Cells 18 : 176–194.
21. YuJ, ZhangL (2005) The transcriptional targets of p53 in apoptosis control. Biochem Biophys Res Commun 331 : 851–858.
22. RileyT, SontagE, ChenP, LevineA (2008) Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol 9 : 402–412.
23. PanierS, DurocherD (2013) Push back to respond better: regulatory inhibition of the DNA double-strand break response. Nat Rev Mol Cell Biol 14 : 661–672.
24. PriceBD, D'AndreaAD (2013) Chromatin remodeling at DNA double-strand breaks. Cell 152 : 1344–1354.
25. SeoaneJ, LeH-V, ShenL, AndersonSA, MassaguéJ (2004) Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell 117 : 211–223.
26. FasanoCA, PhoenixTN, KokovayE, LowryN, ElkabetzY, et al. (2009) Bmi-1 cooperates with Foxg1 to maintain neural stem cell self-renewal in the forebrain. Genes Dev 23 : 561–574.
27. RoqueT, HatonC, EtienneO, ChicheporticheA, RousseauL, et al. (2012) Lack of a p21waf1/cip -dependent G1/S checkpoint in neural stem and progenitor cells after DNA damage in vivo. Stem Cells 30 : 537–547.
28. FazzioTG, PanningB (2010) Condensin complexes regulate mitotic progression and interphase chromatin structure in embryonic stem cells. J Cell Biol 188 : 491–503.
29. Probst AV, AlmouzniG (2011) Heterochromatin establishment in the context of genome-wide epigenetic reprogramming. Trends Genet 27 : 177–185.
30. BreroA, EaswaranHP, NowakD, GrunewaldI, CremerT, et al. (2005) Methyl CpG-binding proteins induce large-scale chromatin reorganization during terminal differentiation. J Cell Biol 169 : 733–743.
31. AgarwalN, BeckerA, JostKL, HaaseS, ThakurBK, et al. (2011) MeCP2 Rett mutations affect large scale chromatin organization. Hum Mol Genet 20 : 4187–4195.
32. McStayB, GrummtI (2008) The epigenetics of rRNA genes: from molecular to chromosome biology. Annu Rev Cell Dev Biol 24 : 131–157.
33. RoosW, KainaB (2006) DNA damage-induced cell death by apoptosis. Trends Mol Med 12 : 440–450.
34. JamesA, WangY, RajeH, RosbyR, DiMarioP (2014) Nucleolar stress with and without p53. Nucleus 5 : 1–25.
35. KuilmanT, MichaloglouC, MooiWJ, PeeperDS (2010) The essence of senescence. Genes Dev 24 : 2463–2479.
36. NaritaM, NunezS, HeardE, NaritaM, LinAW, et al. (2003) Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence state. Cell 113 : 703–716.
37. HayashiMT, CesareAJ, FitzpatrickJAJ, Lazzerini-DenchiE, KarlsederJ (2012) A telomere-dependent DNA damage checkpoint induced by prolonged mitotic arrest. Nat Struct Mol Biol 19 : 387–394.
38. OrthJD, LoewerA, LahavG, MitchisonTJ (2012) Prolonged mitotic arrest triggers partial activation of apoptosis, resulting in DNA damage and p53 induction. Mol Biol Cell 23 : 567–576.
39. GanemN, PellmanD (2012) Linking abnormal mitosis to the acquisition of DNA damage. J Cell Biol 199 : 871–881.
40. BauerCR, HartlTA, BoscoG (2012) Condensin II promotes the formation of chromosome territories by inducing axial compaction of polyploid interphase chromosomes. PLoS Genet 8: e1002873.
41. OnoT, YamashitaD, HiranoT (2013) Condensin II initiates sister chromatid resolution during S phase. J Cell Biol 200 : 429–441.
42. GoslingKM, MakaroffLE, TheodoratosA, KimY-H, WhittleB, et al. (2007) A mutation in a chromosome condensin II subunit, kleisin β, specifically disrupts T cell development. Proc Natl Acad Sci U S A 104 : 12445–12450.
43. RawlingsJS, GatzkaM, ThomasPG, IhleJN (2011) Chromatin condensation via the condensin II complex is required for peripheral T-cell quiescence. EMBO J 30 : 263–276.
44. GuyJ, ChevalH, SelfridgeJ, BirdA (2011) The role of MeCP2 in the brain. Annu Rev Cell Dev Biol 27 : 631–652.
45. SingletonMK, GonzalesML, LeungKN, YasuiDH, SchroederDI, et al. (2011) MeCP2 is required for global heterochromatic and nucleolar changes during activity-dependent neuronal maturation. Neurobiol Dis 43 : 190–200.
46. KishiN, MacklisJD (2004) MECP2 is progressively expressed in post-migratory neurons and is involved in neuronal maturation rather than cell fate decisions. Mol Cell Neurosci 27 : 306–321.
47. ZhengH, YingH, YanH, KimmelmanAC, HillerDJ, et al. (2008) p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation. Nature 455 : 1129–1133.
48. NishideK, NakataniY, KiyonariH, KondoT (2009) Glioblastoma formation from cell population depleted of Prominin1-expressing cells. PLoS One 4: e6869.
49. DávalosV, Súarez-LópezL, CastañoJ, MessentA, AbasoloI, et al. (2012) Human SMC2 protein, a core subunit of human condensin complex, is a novel transcriptional target of the WNT signaling pathway and a new therapeutic target. J Biol Chem 287 : 43472–43481.
50. Murakami-TonamiY, KishidaS, TakeuchiI, KatouY, MarisJM, et al. (2014) Inactivation of SMC2 shows a synergistic lethal response in MYCN-amplified neuroblastoma cells. Cell Cycle 13 : 1115–1131.
51. KankiH, SuzukiH, ItoharaS (2006) High-efficiency CAG-FLPe deleter mice in C57BL/6J background. Exp Anim 55 : 137–141.
52. SakaiK, MiyazakiJI (1997) A transgenic mouse line that retains Cre recombinase activity in mature oocytes irrespective of the cre transgene transmission. Biochem Biophys Res Commun 237 : 318–324.
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