ABL1 regulates spindle orientation in adherent cells and mammalian skin

Nature Communications

Volumn 3, Issue , 2012, Pages

  Matsumura, Shigeru ^a   Hamasaki, Mayumi ^a   Yamamoto, Takuya ^b,c,d   Ebisuya, Miki ^a,d   Sato, Mizuho ^e   Nishida, Eisuke ^a,d   Toyoshima, Fumiko ^a  

^a KYOTO UNIVERSITY   (Japan)

^b KYOTO UNIVERSITY   (Japan)

^c KYOTO UNIVERSITY   (Japan)

^d JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

^e NARA INSTITUTE OF SCIENCE AND TECHNOLOGY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

CELL PROTEIN; LEUCYLGLYCLASPARAGINE REPEAT ENRICHED PROTEIN; NUMA PROTEIN; PROTEIN TYROSINE KINASE; TYROSINE KINASE ABL1; UNCLASSIFIED DRUG; ABELSON KINASE; TYROSINE;

ANIMAL TISSUE; ARTICLE; CELL ADHESION; CELL STRUCTURE; CELLULAR DISTRIBUTION; CONTROLLED STUDY; ENZYME ACTIVITY; EPIDERMIS; HELA CELL; HUMAN; HUMAN CELL; METAPHASE; MICROTUBULE; MITOSIS SPINDLE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; RNA INTERFERENCE; SPINDLE ORIENTATION; WILD TYPE; ANIMAL; CHEMISTRY; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MOUSE MUTANT; PHOSPHORYLATION; PHYSIOLOGY; SIGNAL TRANSDUCTION; SKIN; TIME;

MAMMALIA;

ANIMALS; CELL ADHESION; EPIDERMIS; GENE EXPRESSION REGULATION; HELA CELLS; HUMANS; METAPHASE; MICE; MICE, KNOCKOUT; MITOTIC SPINDLE APPARATUS; PHOSPHORYLATION; PROTO-ONCOGENE PROTEINS C-ABL; RNA INTERFERENCE; SIGNAL TRANSDUCTION; SKIN; TIME FACTORS; TYROSINE;

EID: 84863046015     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms1634     Document Type: Article

References (217)

1. Knoblich, J. A. Mechanisms of asymmetric stem cell division. Cell 132, 583-597 (2008). (Pubitemid 351253698)
2. St Johnston, D. & Ahringer, J. Cell polarity in eggs and epithelia: Parallels and diversity. Cell 141, 757-774 (2010).
3. Quyn, A. J. et al. Spindle orientation bias in gut epithelial stem cell compartments is lost in precancerous tissue. Cell Stem Cell 6, 175-181 (2010).
4. Fleming, E. S., Temchin, M., Wu, Q., Maggio Price, L. & Tirnauer, J. S. Spindle misorientation in tumors from APC(min/+) mice. Mol. Carcinog. 48, 592-598 (2009).
5. Fischer, E. et al. Defective planar cell polarity in polycystic kidney disease. Nat. Genet. 38, 21-23 (2006). (Pubitemid 43011877)
6. Toyoshima, F. & Nishida, E. Integrin-mediated adhesion orients the spindle parallel to the substratum in an EB1-and myosin X-dependent manner. EMBO J. 26, 1487-1498 (2007). (Pubitemid 46480928)
7. Toyoshima, F., Matsumura, S., Morimoto, H., Mitsushima, M. & Nishida, E. PtdIns(3,4,5)P3 regulates spindle orientation in adherent cells. Dev. Cell 13, 796-811 (2007). (Pubitemid 350163038)
8. Mitsushima, M., Toyoshima, F. & Nishida, E. Dual role of Cdc42 in spindle orientation control of adherent cells. Mol. Cell. Biol. 29, 2816-2827 (2009).
9. Lechler, T. & Fuchs, E. Asymmetric cell divisions promote stratification and differentiation of mammalian skin. Nature 437, 275-280 (2005). (Pubitemid 41294492)
10. Taddei, I. et al. Beta1 integrin deletion from the basal compartment of the mammary epithelium affects stem cells. Nat. Cell Biol. 10, 716-722 (2008). (Pubitemid 351772937)
11. Godin, J. D. et al. Huntingtin is required for mitotic spindle orientation and mammalian neurogenesis. Neuron 67, 392-406 (2010).
12. Watt, F. M., Estrach, S. & Ambler, C. A. Epidermal Notch signalling: Differentiation, cancer and adhesion. Curr. Opin. Cell Biol. 20, 171-179 (2008).
13. Schwartzberg, P. L. et al. Mice homozygous for the ablm1 mutation show poor viability and depletion of selected B and T cell populations. Cell 65, 1165-1175 (1991). (Pubitemid 121001330)
14. Tybulewicz, V. L., Crawford, C. E., Jackson, P. K., Bronson, R. T. & Mulligan, R. C. Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogene. Cell 65, 1153-1163 (1991). (Pubitemid 121001329)
15. Konno, D. et al. Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis. Nat. Cell Biol. 10, 93-101 (2008).
16. Du, Q. & Macara, I. G. Mammalian pins is a conformational switch that links NuMA to heterotrimeric G proteins. Cell 119, 503-516 (2004). (Pubitemid 39482350)
17. Siller, K. H. & Doe, C. Q. Spindle orientation during asymmetric cell division. Nat. Cell Biol. 11, 365-374 (2009).
18. Zheng, Z. et al. LGN regulates mitotic spindle orientation during epithelial morphogenesis. J. Cell Biol. 189, 275-288 (2010).
19. Siegrist, S. E. & Doe, C. Q. Microtubule-induced Pins/Galphai cortical polarity in Drosophila neuroblasts. Cell 123, 1323-1335 (2005). (Pubitemid 41821788)
20. Johnston, C. A., Hirono, K., Prehoda, K. E. & Doe, C. Q. Identification of an Aurora-A/PinsLINKER/Dlg spindle orientation pathway using induced cell polarity in S2 cells. Cell 138, 1150-1163 (2009).
21. Merdes, A., Ramyar, K., Vechio, J. D. & Cleveland, D. W. A complex of NuMA and cytoplasmic dynein is essential for mitotic spindle assembly. Cell 87, 447-458 (1996). (Pubitemid 26374319)
22. Du, Q., Stukenberg, P. T. & Macara, I. G. A mammalian partner of inscuteable binds NuMA and regulates mitotic spindle organization. Nat. Cell Biol. 3, 1069-1075 (2001). (Pubitemid 33130457)
23. Kisurina Evgenieva, O. et al. Multiple mechanisms regulate NuMA dynamics at spindle poles. J. Cell Sci. 117, 6391-6400 (2004).
24. Singh, J., Yanfeng, W. A., Grumolato, L., Aaronson, S. A. & Mlodzik, M. Abelson family kinases regulate Frizzled planar cell polarity signaling via Dsh phosphorylation. Genes Dev. 24, 2157-2168 (2010).
25. Segalen, M. et al. The Fz-Dsh planar cell polarity pathway induces oriented cell division via Mud/NuMA in Drosophila and zebrafish. Dev. Cell 19, 740-752 (2010).
26. Kikuchi, K., Niikura, Y., Kitagawa, K. & Kikuchi, A. Dishevelled, a Wnt signalling component, is involved in mitotic progression in cooperation with Plk1. EMBO J. 29, 3470-3483 (2010).
27. Rush, J. et al. Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat. Biotechnol. 23, 94-101 (2005). (Pubitemid 41724631)
28. Dephoure, N. et al. A quantitative atlas of mitotic phosphorylation. Proc. Natl Acad. Sci. USA 105, 10762-10767 (2008).
29. Songyang, Z. et al. Catalytic specificity of protein-tyrosine kinases is critical for selective signalling. Nature 373, 536-539 (1995).
30. Kipreos, E. T. & Wang, J. Y. Differential phosphorylation of c-Abl in cell cycle determined by cdc2 kinase and phosphatase activity. Science 248, 217-220 (1990).
31. Feller, S. M., Ren, R., Hanafusa, H. & Baltimore, D. SH2 and SH3 domains as molecular adhesives: The interactions of Crk and Abl. Trends. Biochem. Sci. 19, 453-458 (1994). (Pubitemid 24342756)
32. Du, Q., Taylor, L., Compton, D. A. & Macara, I. G. LGN blocks the ability of NuMA to bind and stabilize microtubules. A mechanism for mitotic spindle assembly regulation. Curr. Biol. 12, 1928-1933 (2002). (Pubitemid 35426706)
33. Zandy, N. L. & Pendergast, A. M. Abl tyrosine kinases modulate cadherin-dependent adhesion upstream and downstream of Rho family GTPases. Cell Cycle 7, 444-448 (2008). (Pubitemid 351366470)
34. Unno, K., Hanada, T. & Chishti, A. H. Functional involvement of human discs large tumor suppressor in cytokinesis. Exp. Cell Res. 314, 3118-3129 (2008).
35. Fujita, A. et al. Imatinib mesylate (STI571)-induced cell edge translocation of kinase-active and kinase-defective Abelson kinase: Requirements of myristoylation and src homology 3 domain. Mol. Pharmacol. 75, 75-84 (2009).
36. Bell, J. Speakable and Unspeakable in Quantum Mechanics 2nd edn (Cambridge University Press, 2004).
37. Wiseman, H. M., Jones, S. J. & Doherty, A. C. Steering, entanglement, nonlocality, and the Einstein-Podolsky-Rosen paradox. Phys. Rev. Lett. 98, 140402 (2007).
38. Schrödinger, E. Die gegenwärtige Situation in der Quantenmechanik. Naturwissenschaften 23, 807-812; 823-828; 844-849 (1935).
39. Einstein, A., Podolsky, B. & Rosen, N. Can quantum-mechanical description of physical reality be considered complete? Phys. Rev. 47, 777-780 (1935).
40. Oppenheim, J. & Wehner, S. The uncertainty principle determines the nonlocality of quantum mechanics. Science 330, 1072-1074 (2010).
41. Hald, J., Sørensen, J., Schori, C. & Polzik, E. Spin squeezed atoms: A macroscopic entangled ensemble created by light. Phys. Rev. Lett. 83, 1319-1322 (1999). (Pubitemid 129690105)
42. Silberhorn, C. et al. Generation of continuous variable Einstein-Podolsky-Rosen entanglement via the Kerr nonlinearity in an optical fiber. Phys. Rev. Lett. 86, 4267-4270 (2001). (Pubitemid 32469536)
43. Bowen, W., Schnabel, R., Lam, P. & Ralph, T. Experimental investigation of criteria for continuous variable entanglement. Phys. Rev. Lett. 90, 43601 (2003).
44. Howell, J. C., Bennink, R. S., Bentley, S. J. & Boyd, R. W. Realization of the Einstein-Podolsky-Rosen paradox using momentum-and position-entangled photons from spontaneous parametric down conversion. Phys. Rev. Lett. 92, 210403 (2004).
45. Branciard, C., Cavalcanti, E. G., Walborn, S. P., Scarani, V. & Wiseman, H. M. One-sided device-independent quantum key distribution: Security, feasibility and the connection with steering. Preprint at http://arXiv.org/abs/ 1109.1435 (2011).
46. Horodecki, M., Horodecki, P. & Horodecki, R. Separability of mixed states: Necessary and sufficient conditions. Phys. Lett. A 223, 1-8 (1996). (Pubitemid 126391868)
47. Bell, J. S. On the Einstein-Podolsky-Rosen paradox. Physics 1, 195-200 (1964).
48. Cavalcanti, E. G., Jones, S. J., Wiseman, H. M. & Reid, M. D. Experimental criteria for steering and the Einstein-Podolsky-Rosen paradox. Phys. Rev. A 80, 032112 (2009).
49. Saunders, D. J., Jones, S. J., Wiseman, H. M. & Pryde, G. J. Experimental EPR-steering using Bell-local states. Nat. Phys. 6, 845-849 (2010).
50. Pearle, P. M. Hidden-variable example based on data rejection. Phys. Rev. D 2, 1418-1425 (1970).
51. Kim, T., Fiorentino, M. & Wong, F. Phase-stable source of polarization-entangled photons using a polarization Sagnac interferometer. Phys. Rev. A 73, 12316 (2006).
52. Fedrizzi, A., Herbst, T., Poppe, A., Jennewein, T. & Zeilinger, A. A wavelength-tunable fiber-coupled source of narrowband entangled photons. Opt. Express 15, 15377-15386 (2007). (Pubitemid 350127693)
53. Lita, A. E., Miller, A. J. & Nam, S. W. Counting near-infrared single-photons with 95% efficiency. Opt. Express 16, 3032-3040 (2008). (Pubitemid 351342522)
54. Bennink, R. Optimal collinear Gaussian beams for spontaneous parametric down-conversion. Phys. Rev. A 81, 053805 (2010).
55. Scheidl, T. et al. Violation of local realism with freedom of choice. Proc. Natl Acad. Sci. USA 107, 19708-19713 (2010).
56. Wittmann, B. et al. Loophole-free quantum steering. Preprint at http://arXiv.org/abs/1111.0760 (2011).
57. Pironio, S. et al. Device-independent quantum key distribution secure against collective attacks. New J. Phys. 11, 045021 (2009).
58. Walborn, S. P., Salles, A., Gomes, R. M., Toscano, F. & Souto Ribeiro, P. H. Revealing hidden Einstein-Podolsky-Rosen nonlocality. Phys. Rev. Lett. 106, 130402 (2011).
59. Bennet, A. J. et al. Arbitrarily loss-tolerant Einstein-Podolsky-Rosen steering allowing a demonstration over 1 km of optical fiber with no detection loophole. Preprint at http://arXiv.org/abs/1111.0739 (2011).
60. Ma, X. & Lütkenhaus, N. Improved data post-processing in quantum key distribution and application to loss thresholds in device independent QKD Preprint at http://arXiv.org/abs/1109.1203 (2011).
61. Clauser, J. F. & Horne, M. A. Experimental consequences of objective local theories. Phys. Rev. D 10, 526-535 (1974).
62. Eberhard, P. Background level and counter efficiencies required for a loophole-free Einstein-Podolsky-Rosen experiment. Phys. Rev. A 47, 747-750 (1993).
63. Rowe, M. A. et al. Experimental violation of a Bell's inequality with efficient detection. Nature 409, 791-794 (2001). (Pubitemid 32165319)
64. Ansmann, M. et al. Violation of Bell's inequality in Josephson phase qubits. Nature 461, 504-506 (2009).
65. Cavalcanti, E. G., Drummond, P. D., Bachor, H. A. & Reid, M. D. Spin entanglement, decoherence and Bohm's EPR paradox. Opt. Express 17, 18693-18702 (2009).
66. Wehner, S. & Winter, A. Higher entropic uncertainty relations for anti-commuting observables. J. Math. Phys. 49, 062105 (2008).
67. Hecht, E. Optics 4 edn (Addison Wesley, 2002).
68. Moroder, T., Gühne, O., Beaudry, N., Piani, M. & Lütkenhaus, N. Entanglement verification with realistic measurement devices via squashing operations. Phys. Rev. A 81, 052342 (2010).
69. Lydersen, L. et al. Superlinear threshold detectors in quantum cryptography. Phys. Rev. A 84, 032320 (2011).
70. Gerhardt, I., Liu, Q., Lamas-Linares, A., Skaar, J., Kurtsiefer, C. & Makarov, V. Full-field implementation of a perfect eavesdropper on a quantum cryptography system. Nat. Commun. 2, 349 (2011).
71. Shimada, M. et al. Progress in the ITER physics basis-Chapter 1: Overview and summary. Nucl. Fusion 47, S1-S17 (2007).
72. Evans, T. E. et al. Edge stability and transport control with resonant magnetic perturbations in collisionless tokamak plasmas. Nat. Phys. 2, 419-423 (2006). (Pubitemid 43841618)
73. Liang, Y. et al. Active control of type-I edge localized modes on JET. Phys. Rev. Lett. 98, 265004 (2007).
74. Goeler, S., von Stodiek, W. & Sauthoff, N. Studies of internal disruptions and m=1 oscillations in tokamak discharges with soft-x-ray techniques. Phys. Rev. Lett. 33, 1201-1204 (1974).
75. Campbell, D. J. et al. Stabilization of sawteeth with additional heating in the JET tokamak. Phys. Rev. Lett. 60, 2148-2151 (1988).
76. Sauter, O. et al. Control of neoclassical tearing modes by sawtooth control. Phys. Rev. Lett. 88, 105001 (2002).
77. Chapman, I. T. et al. Empirical scaling of sawtooth period for onset of neoclassical tearing modes. Nucl. Fusion 50, 102001 (2010).
78. White, R. B., Monticello, D. A., Rosenbluth, M. N. & Waddel, B. V. Saturation of tearing mode. Phys. Fluids 20, 800-805 (1977).
79. Romanelli, F. et al. Overview of JET results. Fusion Energy 2010: Proceedings of the 23rd International Conference, Daejeon, 2010 (International Atomic Energy Agency (IAEA), 2010).
80. Winsor, N., Johnson, J. L. & Dawson, J. M. Geodesic acoustic waves in hydromagnetic systems. Phys. Fluids 11, 2448-2450 (1968).
81. Porcelli, F. & Rosenbluth, M. N. Generalised Mercier criterion. Plasma Phys. Control. Fusion 40, 481-492 (1998).
82. White, R. B., Rutherford, P. H., Colestock, P. & Bussac, M. N. Sawtooth stabilization by energetic trapped particles. Phys. Rev. Lett. 60, 2038-2048 (1988).
83. Porcelli, F. Fast particle stabilization. Plasma Phys. Control. Fusion 33, 1601-1620 (1991).
84. Cheng, C. Z. & Qian, Q. Theory of ballooning-mirror instabilities for anisotropic pressure plasmas in the magnetosphere. J. Geophys. Res. 99, 11193-11209 (1994).
85. Brouwer, L. E. J. On continuous vector distributions on surfaces. Nederl. Akad. Wetensch. Proc. Ser. A 11, 850-858 (1909).
86. Antonsen, T. M. & Lee, Y. C. Electrostatic modification of variational-principles for anisotropic plasmas. Phys. Fluids 25, 132-1342 (1982).
87. Van Dam, J. W., Rosenbluth, M. N. & Lee, Y. C. A generalized kinetic-energy principle. Phys. Fluids 25, 1349-1354 (1982).
88. Helander, P., Gimblett, C. G., Hastie, R. J. & McClements, K. G. The influence of fast ions on the magnetohydrodynamic stability of negative shear profiles. Phys. Plasmas 4, 2181-2187 (1997). (Pubitemid 127649788)
89. Rosenbluth, M. N., Dagazian, P. Y. & Rutherford, P. H. Nonlinear properties of internal m=1 kink instability in cylindrical tokamak. Phys. Fluids 16, 1894-1902 (1973).
90. Mercier, C. Un critere necessaire de stabilite hydromagnetique pour un plasma en symetrie de revolution. Nucl. Fusion 1, 47-53 (1960).
91. Cheng, C. Z., Chen, L. & Chance, M. S. High-n ideal and resistive Alfven waves in tokamaks. Ann. Phys. 161, 21 (1985).
92. Bondeson, A. & Ward, D. Stabilization of external-modes in tokamaks by resistive walls and plasma rotation. Phys. Rev. Lett. 72, 2709-2712 (1994). (Pubitemid 24975240)
93. Graves, J. P., Chapman, I. T., Coda, S., Eriksson, L.-G. & Johnson, T. Sawtooth-control mechanism using toroidally propagating ion-cyclotron- resonance waves in tokamaks. Phys. Rev. Lett. 102, 065005 (2009).
94. Graves, J. P. et al. Experimental verification of sawtooth control by energetic particles in ion cyclotron resonance heated JET tokamak plasmas. Nucl. Fusion 50, 052002 (2010).
95. Betti, R. & Freidberg, J. P. Destabilization of the internal kink mode by energetic circulating ions. Phys. Rev. Lett. 70, 3428-3430 (1993).
96. Chapman, I. T. Controlling sawtooth oscillations in tokamak plasmas. Plasma Phys. Control. Fus. 53, 003001 (2011).
97. Graves, J. P. et al. Recent advances in sawtooth control. Fus. Sci. Tech. 59, 539-548 (2011).
98. Albergante, M. et al. Numerical modelling of electromagnetic turbulent transport of energetic ions in burning plasmas. Plasma Phys. Control. Fusion 53, 054002 (2011).
99. Graves, J. P. Influence of asymmetric energetic ion distributions on sawtooth stabilization. Phys. Rev. Lett. 92, 185003 (2004).
100. Chapman, I. T. et al. Sawtooth control using off-axis NBI. Plasma Phys. Control. Fusion 50, 045006 (2008).
101. Jucker, M. et al. Integrated modeling for ion cyclotron resonant heating in toroidal systems. Comp. Phys. Comm. 182, 912-925 (2011).
102. Wagner, F. et al. Regime of improved confinement and high-beta in neutral-beam-heated divertor discharges of the asdex tokamak. Phys. Rev. Lett. 49, 1408-1412 (1982).
103. Pinches, S. D., Appel, L., Candy, J., Hender, T. & Hopcraft, K. I. The HAGIS self-consistent nonlinear wave-particle interaction model. Comput. Phys. Commun. 111, 133-149 (1998). (Pubitemid 128400470)
104. Lennholm, M. et al. Demonstration of effective control of fast-ion-stabilized sawteeth by electron-cyclotron current drive. Phys. Rev. Lett. 102, 115004 (2009).
105. Akala, O. O. & Clarke, M. F. Hematopoietic stem cell self-renewal. Curr. Opin. Genet. Dev. 16, 496-501 (2006). (Pubitemid 44345208)
106. Bracken, A. P. & Helin, K. Polycomb group proteins: Navigators of lineage pathways led astray in cancer. Nat. Rev. Cancer 9, 773-784 (2009).
107. Margueron, R. & Reinberg, D. The Polycomb complex PRC2 and its mark in life. Nature 469, 343-349 (2011).
108. Ben-Porath, I. et al. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat. Genet. 40, 499-507 (2008). (Pubitemid 351601215)
109. Schlesinger, Y. et al. Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nat. Genet. 39, 232-236 (2007). (Pubitemid 46184355)
110. Martin-Perez, D., Piris, M. A. & Sanchez-Beato, M. Polycomb proteins in hematologic malignancies. Blood 116, 5465-5475 (2010).
111. Morin, R. D. et al. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat. Genet. 42, 181-185 (2010).
112. Sneeringer, C. J. et al. Coordinated activities of wild-type plus mutant EZH2 drive tumor-associated hypertrimethylation of lysine 27 on histone H3 (H3K27) in human B-cell lymphomas. Proc. Natl Acad. Sci. U S A 107, 20980-20985 (2011).
113. Yap, D. B. et al. Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation. Blood 117, 2451-2459 (2010).
114. Xu, F. et al. Overexpression of the EZH2, RING1 and BMI1 genes is common in myelodysplastic syndromes: Relation to adverse epigenetic alteration and poor prognostic scoring. Ann. Hematol. 90, 643-653 (2010).
115. Paul, T. A. et al. Signatures of polycomb repression and reduced H3K4 trimethylation are associated with p15INK4b DNA methylation in AML. Blood 115, 3098-3108 (2010).
116. Fiskus, W. et al. Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor panobinostat against human AML cells. Blood 114, 2733-2743 (2009).
117. Nikoloski, G. et al. Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes. Nat. Genet. 42, 665-667 (2010).
118. Ernst, T. et al. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat. Genet. 42, 722-726 (2010).
119. de Boer, J. et al. Transgenic mice with hematopoietic and lymphoid specific expression of Cre. Eur. J. Immunol. 33, 314-325 (2003).
120. Croker, B. A. et al. SOCS3 is a critical physiological negative regulator of G-CSF signaling and emergency granulopoiesis. Immunity 20, 153-165 (2004). (Pubitemid 38258392)
121. Ogilvy, S. et al. Promoter elements of vav drive transgene expression in vivo throughout the hematopoietic compartment. Blood 94, 1855-1863 (1999). (Pubitemid 29430401)
122. Goodell, M. A. et al. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J. Exp. Med. 183, 1797-1806 (1996). (Pubitemid 26134320)
123. Ventura, A. et al. Restoration of p53 function leads to tumour regression in vivo. Nature 445, 661-665 (2007). (Pubitemid 46232887)
124. Clausen, B. E. et al. Conditional gene targeting in macrophages and granulocytes using LysMcre mice. Transgenic Res. 8, 265-277 (1999). (Pubitemid 29523965)
125. Passegue, E. et al. Global analysis of proliferation and cell cycle gene expression in the regulation of hematopoietic stem and progenitor cell fates. J. Exp. Med. 202, 1599-1611 (2005). (Pubitemid 41746605)
126. Ashburner, M. et al. Gene ontology: Tool for the unification of biology. The gene ontology consortium. Nat. Genet. 25, 25-29 (2000). (Pubitemid 30257031)
127. Kiel, M. J., Radice, G. L. & Morrison, S. J. Lack of evidence that hematopoietic stem cells depend on N-cadherin-mediated adhesion to osteoblasts for their maintenance. Cell Stem Cell 1, 204-217 (2007). (Pubitemid 47215590)
128. Arai, F. et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 118, 149-161 (2004). (Pubitemid 38962572)
129. Tam, W. F. et al. Id1 is a common downstream target of oncogenic tyrosine kinases in leukemic cells. Blood 112, 1981-1992 (2008).
130. Forsberg, E. C. et al. Molecular signatures of quiescent, mobilized and leukemia-initiating hematopoietic stem cells. PLoS One 5, e8785 (2010).
131. Buonamici, S. et al. EVI1 induces myelodysplastic syndrome in mice. J. Clin. Invest. 114, 713-719 (2004). (Pubitemid 39582822)
132. Goyama, S. et al. Evi-1 is a critical regulator for hematopoietic stem cells and transformed leukemic cells. Cell Stem Cell 3, 207-220 (2008).
133. Goyama, S. et al. EVI-1 interacts with histone methyltransferases SUV39H1 and G9a for transcriptional repression and bone marrow immortalization. Leukemia 24, 81-88 (2010).
134. Bracken, A. P. et al. The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev. 21, 525-530 (2007). (Pubitemid 46409467)
135. Sauvageau, M. & Sauvageau, G. Polycomb group proteins: Multi-faceted regulators of somatic stem cells and cancer. Cell Stem Cell 7, 299-313 (2010).
136. Tefferi, A. & Gilliland, D. G. Oncogenes in myeloproliferative disorders. Cell Cycle 6, 550-566 (2007). (Pubitemid 46440428)
137. Kogan, S. C. et al. Bethesda proposals for classification of nonlymphoid hematopoietic neoplasms in mice. Blood 100, 238-245 (2002). (Pubitemid 35177453)
138. Vire, E. et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature 439, 871-874 (2006). (Pubitemid 43255707)
139. Ohm, J. E. et al. A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing. Nat. Genet. 39, 237-242 (2007). (Pubitemid 46184356)
140. Widschwendter, M. et al. Epigenetic stem cell signature in cancer. Nat. Genet. 39, 157-158 (2007). (Pubitemid 46184343)
141. Coussens, L. M. & Werb, Z. Inflammation and cancer. Nature 420, 860-867 (2002). (Pubitemid 36019639)
142. Jones, P. A. & Baylin, S. B. The epigenomics of cancer. Cell 128, 683-692 (2007). (Pubitemid 46273572)
143. Bejar, R. et al. Clinical effect of point mutations in myelodysplastic syndromes. N. Engl. J. Med. 364, 2496-2506 (2011).
144. Lund, A. H. & van Lohuizen, M. Polycomb complexes and silencing mechanisms. Curr. Opin. Cell Biol. 16, 239-246 (2004). (Pubitemid 38610403)
145. Passegue, E. & Wagers, A. J. Regulating quiescence: New insights into hematopoietic stem cell biology. Dev. Cell 10, 415-417 (2006).
146. Li, Q. et al. Hematopoiesis and leukemogenesis in mice expressing oncogenic NrasG12D from the endogenous locus. Blood 117, 2022-2032 (2011).
147. Cleary, M. L. Regulating the leukaemia stem cell. Best Pract. Res. Clin. Haematol. 22, 483-487 (2009).
148. Braun, B. S. et al. Somatic activation of oncogenic Kras in hematopoietic cells initiates a rapidly fatal myeloproliferative disorder. Proc. Natl Acad. Sci. U S A 101, 597-602 (2004). (Pubitemid 38084682)
149. Mullally, A. et al. Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietic stem and progenitor cells. Cancer Cell 17, 584-596 (2010).
150. Warr, M. R., Pietras, E. M. & Passegue, E. Mechanisms controlling hematopoietic stem cell functions during normal hematopoiesis and hematological malignancies. Wiley Interdiscip. Rev. Syst. Biol. Med. 3, 681-701 (2011).
151. Herrera-Merchan, A. et al. miR-33-mediated downregulation of p53 controls hematopoietic stem cell self-renewal. Cell Cycle 9, 3277-3285 (2010).
152. Gonzalez, S., Pisano, D. G. & Serrano, M. Mechanistic principles of chromatin remodeling guided by siRNAs and miRNAs. Cell Cycle 7, 2601-2608 (2008).
153. Gonzalez, S. et al. Oncogenic activity of Cdc6 through repression of the INK4/ARF locus. Nature 440, 702-706 (2006).
154. Hirokawa, N., Tanaka, Y., Okada, Y. & Takeda, S. Nodal flow and the generation of left-right asymmetry. Cell 125, 33-45 (2006).
155. Gros, J., Feistel, K., Viebahn, C., Blum, M. & Tabin, C. J. Cell movements at Hensen's node establish left/right asymmetric gene expression in the chick. Science 324, 941-944 (2009).
156. Hamada, H., Meno, C., Watanabe, D. & Saijoh, Y. Establishment of vertebrate left-right asymmetry. Nat. Rev. Genet. 3, 103-113 (2002). (Pubitemid 34506594)
157. Nonaka, S. et al. Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein. Cell 95, 829-837 (1998). (Pubitemid 29014462)
158. Nonaka, S., Shiratori, H., Saijoh, Y. & Hamada, H. Determination of left-right patterning of the mouse embryo by artificial nodal flow. Nature 418, 96-99 (2002). (Pubitemid 34742578)
159. Okada, Y., Takeda, S., Tanaka, Y., Belmonte, J. C. & Hirokawa, N. Mechanism of nodal flow: A conserved symmetry breaking event in left-right axis determination. Cell 121, 633-644 (2005). (Pubitemid 40720015)
160. Nonaka, S. et al. De novo formation of left-right asymmetry by posterior tilt of nodal cilia. PLoS Biol. 3, e268 (2005).
161. Hashimoto, M. et al. Planar polarization of node cells determines the rotational axis of node cilia. Nat. Cell Biol. 12, 170-176 (2010).
162. Cartwright, J. H., Piro, O. & Tuval, I. Fluid-dynamical basis of the embryonic development of left-right asymmetry in vertebrates. Proc. Natl Acad. Sci. USA 101, 7234-7239 (2004). (Pubitemid 38638016)
163. McGrath, J., Somlo, S., Makova, S., Tian, X. & Brueckner, M. Two populations of node monocilia initiate left-right asymmetry in the mouse. Cell 114, 61-73 (2003). (Pubitemid 36859841)
164. Tanaka, Y., Okada, Y. & Hirokawa, N. FGF-induced vesicular release of Sonic hedgehog and retinoic acid in leftward nodal flow is critical for left-right determination. Nature 435, 172-177 (2005). (Pubitemid 40685936)
165. Afzelius, B. A. A human syndrome caused by immotile cilia. Science 193, 317-319 (1976).
166. Shinohara, K. et al. High-speed micro-PIV measurements of transient flow in microfluidic devices. Meas. Sci. Technol. 15, 1965-1970 (2004). (Pubitemid 39375770)
167. Schweickert, A. et al. The nodal inhibitor coco is a critical target of leftward flow in Xenopus. Curr. Biol. 20, 738-743 (2010).
168. Schweickert, A. et al. Cilia-driven leftward flow determines laterality in Xenopus. Curr. Biol. 17, 60-66 (2007). (Pubitemid 46027569)
169. Shiratori, H. et al. Two-step regulation of left-right asymmetric expression of Pitx2: Initiation by nodal signaling and maintenance by Nkx2. Mol. Cell 7, 137-149 (2001). (Pubitemid 32162907)
170. Kobayashi, Y. et al. Hydrocephalus, situs inversus, chronic sinusitis, and male infertility in DNA polymerase lambda-deficient mice: Possible implication for the pathogenesis of immotile cilia syndrome. Mol. Cell Biol. 22, 2769-2776 (2002). (Pubitemid 34262997)
171. Bonnafe, E. et al. The transcription factor RFX3 directs nodal cilium development and left-right asymmetry specification. Mol. Cell Biol. 24, 4417-4427 (2004). (Pubitemid 41071011)
172. Okada, Y. et al. Abnormal nodal flow precedes situs inversus in iv and inv mice. Mol. Cell 4, 459-468 (1999). (Pubitemid 29531126)
173. Yokoyama, T. et al. Reversal of left-right asymmetry: A situs inversus mutation. Science 260, 679-682 (1993). (Pubitemid 23167591)
174. Oki, S. et al. Reversal of left-right asymmetry induced by aberrant Nodal signaling in the node of mouse embryos. Development 136, 3917-3925 (2009).
175. Vick, P. et al. Flow on the right side of the gastrocoel roof plate is dispensable for symmetry breakage in the frog Xenopus laevis. Dev. Biol. 331, 281-291 (2009).
176. Cartwright, J. H., Piro, N., Piro, O. & Tuval, I. Embryonic nodal flow and the dynamics of nodal vesicular parcels. J. R. Soc. Interface 4, 49-55 (2007). (Pubitemid 46225430)
177. Happel, K. & Brenner, H. Low Reynolds Number Hydrodynamics (Martinus Nijhoff, 1983).
178. Nauli, S. M. et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat. Genet. 33, 129-137 (2003). (Pubitemid 36177063)
179. Malone, A. M. et al. Primary cilia mediate mechanosensing in bone cells by a calcium-independent mechanism. Proc. Natl Acad. Sci. USA 104, 13325-13330 (2007). (Pubitemid 47293944)
180. Tabin, C. J. & Vogan, K. J. A two-cilia model for vertebrate left-right axis specification. Genes Dev. 17, 1-6 (2003). (Pubitemid 36062503)
181. Kawasumi, A. et al. Left-right asymmetry in the level of active Nodal protein produced in the node is translated into left-right asymmetry in the lateral plate of mouse embryos. Dev. Biol. 353, 321-330 (2011).
182. Robinson, J. et al. The IMGT/HLA database. Nucleic Acids Res. 37, 1013-1017 (2009).
183. Spurgin, L. G. & Richardson, D. S. How pathogens drive genetic diversity: MHC, mechanisms and misunderstandings. Proc. R. Soc. B Biol. Sci. 277, 979-988 (2010).
184. Janeway, C. A., Travers, P., Walport, M. & Sclomchik, M. J. Immunobiology: The Immune System in Health and Disease 6th edn (Garland Science, 2005).
185. Bernatchez, L. & Landry, C. MHC studies in nonmodel vertebrates: What have we learned about natural selection in 15 years? J. Evol. Biol. 16, 363-377 (2003). (Pubitemid 36567968)
186. Barrett, R. D. H. & Schluter, D. Adaptation from standing genetic variation. Trends Ecol. Evol. 23, 38-44 (2008).
187. Sorci, G., Moller, A. P. & Boulinier, T. Genetics of host-parasite interactions. Trends Ecol. Evol. 12, 196-200 (1997).
188. Edwards, S. V. & Hedrick, P. W. Evolution and ecology of MHC molecules: From genomics to sexual selection. Trends Ecol. Evol. 13, 305-311 (1998). (Pubitemid 28368430)
189. Milinski, M. The major histocompatibility complex, sexual selection, and mate choice. Annu. Rev. Ecol. Evol. Syst. 37, 159-186 (2006). (Pubitemid 44907616)
190. De Boer, R. J., Borghans, J. A. M., van Boven, M., Kesmir, C. & Weissing, F. J. Heterozygote advantage fails to explain the high degree of polymorphism of the MHC. Immunogenetics 55, 725-731 (2004). (Pubitemid 38316677)
191. Ding, A. & Goudet, J. Heterozygote advantage and the maintenance of polymorphism for multilocus traits. Theor. Popul. Biol. 68, 157-166 (2005). (Pubitemid 41415588)
192. Wegner, K. M., Kalbe, M., Kurtz, J., Reusch, T. B. H. & Milinski, M. Parasite selection for immunogenetic optimality. Science 301, 1343 (2003). (Pubitemid 37075801)
193. Takahata, N. & Nei, M. Allelic genealogy under overdominant and frequency-dependent selection and polymorphism of major histocompatibility complex loci. Genetics 124, 967-978 (1990). (Pubitemid 20146073)
194. Slade, R. W. & McCallum, H. I. Overdominant vs. frequency-dependent selection at MHC Loci. Genetics 132, 861-862 (1992).
195. Lohm, J. et al. Experimental evidence for major histocompatibility complex-allele-specific resistance to a bacterial infection. Proc. R. Soc. B Biol. Sci. 269, 2029-2033 (2002). (Pubitemid 35177013)
196. Hamilton, W., Axelrod, R. & Tanese, R. Sexual reproduction as an adaptation to resist parasites. Proc. Natl Acad. Sci. USA 87, 3566-3573 (1990).
197. Howard, R. S. & Lively, C. M. Good vs complementary genes for parasitic resistance and the evolution of mate choice. BMC Evol. Biol. 4, 1-7 (2004).
198. Eizaguirre, C., Yeates, S. E., Lenz, T. L., Kalbe, M. & Milinski, M. MHC-based mate choice combines good genes and maintenance of MHC polymorphism. Mol. Ecol. 18, 3316-3329 (2009).
199. Westerdahl, H., Hansson, B., Bensch, S. & Hasselquist, D. Between-year variation of MHC allele frequencies in great reed warblers: Selection or drift? J. Evol. Biol. 17, 485-492 (2004). (Pubitemid 38571944)
200. Hess, C., Wang, Z. & Edwards, S. Evolutionary genetics of Carpodacus mexicanus, a recently colonized host of a bacterial pathogen, Mycoplasma gallisepticum. Genetica 129, 217 (2007).
201. Wegner, K. M. Major Histocompatibility Genes, Polymorphism and Balancing Selection: The Case of Parasites and Sticklebacks PhD Thesis (Christian-Albrechts-University, 2004).
202. Charbonnel, N. & Pemberton, J. A long-term genetic survey of an ungulate population reveals balancing selection acting on MHC through spatial and temporal fluctuations in selection. Heredity 95, 377-388 (2005). (Pubitemid 41548413)
203. Ekblom, R. et al. Spatial pattern of MHC class II variation in the great snipe (Gallinago media). Mol. Ecol. 16, 1439-1451 (2007). (Pubitemid 46474783)
204. Loiseau, C. et al. Plasmodium relictum infection and MHC diversity in the house sparrow (Passer domesticus). Proc. R. Soc. B Biol. Sci. 278, 1264-1272 (2011).
205. Van Valen, L. A new evolutionary law. Evol. Theor. 1, 1-30 (1973).
206. Lively, C. M. & Dybdahl, M. F. Parasite adaptation to locally common host genotypes. Nature 405, 679-681 (2000). (Pubitemid 30428652)
207. Lenz, T. L., Eizaguirre, C., Becker, S. & Reusch, T. B. H. RSCA genotyping of MHC for high-throughput evolutionary studies in the model organism three-spined stickleback Gasterosteus aculeatus. BMC Evol. Biol. 9, 57 (2009).
208. Hamilton, W. D. & Zuk, M. Heritable true fitness and bright birds: A role for parasites? Science 218, 384-387 (1982). (Pubitemid 13283877)
209. Decaestecker, E. et al. Host-parasite/'Red Queen/' dynamics archived in pond sediment. Nature 450, 870 (2007).
210. Koskella, B. & Lively, C. M. Evidence for negative frequency-dependent selection during experimental coevolution of a freshwater snail and a sterilizing trematode. Evolution 63, 2213-2221 (2009).
211. Berenos, C., Wegner, K. M. & Schmid-Hempel, P. Antagonistic coevolution with parasites maintains host genetic diversity: An experimental test. Proc. R. Soc. B Biol. Sci. 278, 218-224 (2011).
212. Schulte, R. D., Makus, C., Hasert, B., Michiels, N. K. & Schulenburg, H. Multiple reciprocal adaptations and rapid genetic change upon experimental coevolution of an animal host and its microbial parasite. Proc. Natl Acad. Sci. USA 107, 7359-7364 (2010).
213. Kalbe, M. et al. Lifetime reproductive success is maximized with optimal MHC diversity. Proc. R. Soc. B Biol. Sci. 276, 925-934 (2009).
214. Lenz, T. L. & Becker, S. Simple approach to reduce PCR artefact formation leads to reliable genotyping of MHC and other highly polymorphic loci-implications for evolutionary analysis. Gene 427, 17-123 (2008).
215. Clarke, K. R. & Gorley, R. N. Primer v6: User Manual/Tutorial (PRIMER-E, 2006).
216. R Development Core Team. R Foundation for Statistical Computing (2010).
217. Eizaguirre, C. et al. Parasite diversity, patterns of MHC II variation and olfactory based mate choice in diverging three-spined stickleback ecotypes. Evol. Ecol. 25, 605-622 (2011).