Cell cycle regulation in the postmitotic neuron: oxymoron or new biology? (original) (raw)

• Cai, L., Hayes, N. L. & Nowakowski, R. S. Synchrony of clonal cell proliferation and contiguity of clonally related cells: production of mosaicism in the ventricular zone of developing mouse neocortex. J. Neurosci. 17, 2088–2100 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Cai, L., Hayes, N. L. & Nowakowski, R. S. Local homogeneity of cell cycle length in developing mouse cortex. J. Neurosci. 17, 2079–2087 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Takahashi, T., Goto, T., Miyama, S., Nowakowski, R. S. & Caviness, V. S. Jr. Sequence of neuron origin and neocortical laminar fate: relation to cell cycle of origin in the developing murine cerebral wall. J. Neurosci. 19, 10357–10371 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Takahashi, T., Nowakowski, R. S. & Caviness, V. S. Jr. The cell cycle of the pseudostratified ventricular epithelium of the embryonic murine cerebral wall. J. Neurosci. 15, 6046–6057 (1995).
  Article CAS PubMed PubMed Central Google Scholar
• Takahashi, T., Nowakowski, R. S. & Caviness, V. S. Jr. Cell cycle parameters and patterns of nuclear movement in the neocortical proliferative zone of the fetal mouse. J. Neurosci. 13, 820–833 (1993).
  Article CAS PubMed PubMed Central Google Scholar
• Miale, I. L. & Sidman, R. L. An autoradiographic analysis of histogenesis in the mouse cerebellum. Exp. Neurol. 4, 277–296 (1961).
  Article CAS PubMed Google Scholar
• Uzman, L. L. The histogenesis of the mouse cerebellum as studied by its tritiated thymidine uptake. J. Comp. Neurol. 114, 137–159 (1960).
  Article CAS PubMed Google Scholar
• Nowakowski, R. S., Lewin, S. B. & Miller, M. W. Bromodeoxyuridine immunohistochemical determination of the lengths of the cell cycle and the DNA-synthetic phase for an anatomically defined population. J. Neurocyt. 18, 311–318 (1989).
  Article CAS Google Scholar
• Bonnert, T. P. et al. Molecular characterization of adult mouse subventricular zone progenitor cells during the onset of differentiation. Eur. J. Neurosci. 24, 661–675 (2006).
  Article PubMed Google Scholar
• Noctor, S. C., Martinez-Cerdeno, V., Ivic, L. & Kriegstein, A. R. Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nature Neurosci. 7, 136–144 (2004).
  Article CAS PubMed Google Scholar
• Taupin, P. Neurogenesis in the adult central nervous system. C. R. Biol. 329, 465–475 (2006).
  Article PubMed Google Scholar
• Sohur, U. S., Emsley, J. G., Mitchell, B. D. & Macklis, J. D. Adult neurogenesis and cellular brain repair with neural progenitors, precursors and stem cells. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 361, 1477–1497 (2006).
  Article CAS PubMed Google Scholar
• Aimone, J. B., Wiles, J. & Gage, F. H. Potential role for adult neurogenesis in the encoding of time in new memories. Nature Neurosci. 9, 723–727 (2006).
  Article CAS PubMed Google Scholar
• Kuan, C. Y. et al. Hypoxia-ischemia induces DNA synthesis without cell proliferation in dying neurons in adult rodent brain. J. Neurosci. 24, 10763–10772 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Kenney, A. M., Cole, M. D. & Rowitch, D. H. Nmyc upregulation by sonic hedgehog signaling promotes proliferation in developing cerebellar granule neuron precursors. Development 130, 15–28 (2003).
  Article CAS PubMed Google Scholar
• Ruiz i Altaba, A., Palma, V. & Dahmane, N. Hedgehog–Gli signalling and the growth of the brain. Nature Rev. Neurosci. 3, 24–33 (2002).
  Article CAS Google Scholar
• Clarke, A. R. et al. Requirement for a functional _Rb_-1 gene in murine development. Nature 359, 328–330 (1992).
  Article CAS PubMed Google Scholar
• Jacks, T. et al. Effects of an Rb mutation in the mouse. Nature 359, 295–300 (1992).
  Article CAS PubMed Google Scholar
• Lee, E. Y. et al. Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis. Nature 359, 288–294 (1992).
  Article CAS PubMed Google Scholar
• Lee, E. Y. et al. Dual roles of the retinoblastoma protein in cell cycle regulation and neuron differentiation. Genes Dev. 8, 2008–2021 (1994). A detailed description of how a cell cycle protein can also be a potent pro-differentiation agent.
  Article CAS PubMed Google Scholar
• Cunningham, J. J. & Roussel, M. F. Cyclin-dependent kinase inhibitors in the development of the central nervous system. Cell Growth Differ. 12, 387–396 (2001).
  CAS PubMed Google Scholar
• Cunningham, J. J. et al. The cyclin-dependent kinase inhibitors p19Ink4d and p27Kip1 are coexpressed in select retinal cells and act cooperatively to control cell cycle exit. Mol. Cell. Neurosci. 19, 359–374 (2002). A clear demonstration of how certain CKIs assist in the orderly cessation of neuronal cell division.
  Article CAS PubMed Google Scholar
• Schmetsdorf, S., Gartner, U. & Arendt, T. Expression of cell cycle-related proteins in developing and adult mouse hippocampus. Int. J. Dev. Neurosci. 23, 101–112 (2005).
  Article CAS PubMed Google Scholar
• Blackshaw, S. et al. Genomic analysis of mouse retinal development. PLoS Biol. 2, E247 (2004).
  Article PubMed PubMed Central CAS Google Scholar
• Dehay, C., Savatier, P., Cortay, V. & Kennedy, H. Cell-cycle kinetics of neocortical precursors are influenced by embryonic thalamic axons. J. Neurosci. 21, 201–214 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Lukaszewicz, A. et al. G1 phase regulation, area-specific cell cycle control, and cytoarchitectonics in the primate cortex. Neuron 47, 353–364 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Gao, Y. et al. A critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis. Cell 95, 891–902 (1998).
  Article CAS PubMed Google Scholar
• Barnes, D. E., Stamp, G., Rosewell, I., Denzel, A. & Lindahl, T. Targeted disruption of the gene encoding DNA ligase IV leads to lethality in embryonic mice. Curr. Biol. 8, 1395–1398 (1998).
  Article CAS PubMed Google Scholar
• Esposito, G. et al. Mice reconstituted with DNA polymerase β-deficient fetal liver cells are able to mount a T cell-dependent immune response and mutate their Ig genes normally. Proc. Natl Acad. Sci. USA 97, 1166–1171 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Sugo, N., Aratani, Y., Nagashima, Y., Kubota, Y. & Koyama, H. Neonatal lethality with abnormal neurogenesis in mice deficient in DNA polymerase β. EMBO J. 19, 1397–1404 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Lee, Y., Barnes, D. E., Lindahl, T. & McKinnon, P. J. Defective neurogenesis resulting from DNA ligase IV deficiency requires Atm. Genes Dev. 14, 2576–2580 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Chun, J. Cell death, DNA breaks and possible rearrangements: an alternative view. Trends Neurosci. 23, 407–409 (2000).
  Article CAS PubMed Google Scholar
• Gilmore, E. C., Herrup, K., Nowakowski, R. S. & Caviness, V. S. Jr. Reply. Trends Neurosci. 23, 408–409 (2000).
  Article CAS PubMed Google Scholar
• Gilmore, E. C., Nowakowski, R. S., Caviness, V. S. Jr. & Herrup, K. Cell birth, cell death, cell diversity and DNA breaks: how do they all fit together? Trends Neurosci. 23, 100–105 (2000).
  Article CAS PubMed Google Scholar
• Baker, S. J. & McKinnon, P. J. Tumour-suppressor function in the nervous system. Nature Rev. Cancer 4, 184–196 (2004).
  Article CAS Google Scholar
• O'Driscoll, M. & Jeggo, P. A. The role of double-strand break repair- insights from human genetics. Nature Rev. Genet. 7, 45–54 (2006).
  Article CAS PubMed Google Scholar
• Murphy, M. et al. Delayed early embryonic lethality following disruption of the murine cyclin A2 gene. Nature Genet. 15, 83–86 (1997).
  Article CAS PubMed Google Scholar
• Brandeis, M. et al. Cyclin B2-null mice develop normally and are fertile whereas cyclin B1-null mice die in utero. Proc. Natl Acad. Sci. USA 95, 4344–4349 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Kozar, K. et al. Mouse development and cell proliferation in the absence of D-cyclins. Cell 118, 477–491 (2004).
  Article CAS PubMed Google Scholar
• Levine, E. M., Close, J., Fero, M., Ostrovsky, A. & Reh, T. A. p27Kip1 regulates cell cycle withdrawal of late multipotent progenitor cells in the mammalian retina. Dev. Biol. 219, 299–314 (2000).
  Article CAS PubMed Google Scholar
• Mitsuhashi, T. et al. Overexpression of p27Kip1 lengthens the G1 phase in a mouse model that targets inducible gene expression to central nervous system progenitor cells. Proc. Natl Acad. Sci. USA 98, 6435–6440 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Ciemerych, M. A. & Sicinski, P. Cell cycle in mouse development. Oncogene 24, 2877–2898 (2005). This is a comprehensive yet readable overview of virtually every cell cycle gene knockout in mice.
  Article CAS PubMed Google Scholar
• al-Ubaidi, M. R., Hollyfield, J. G., Overbeek, P. A. & Baehr, W. Photoreceptor degeneration induced by the expression of simian virus 40 large tumor antigen in the retina of transgenic mice. Proc. Natl Acad. Sci. USA 89, 1194–1198 (1992).
  Article CAS PubMed PubMed Central Google Scholar
• Feddersen, R. M., Clark, H. B., Yunis, W. S. & Orr, H. T. In vivo viability of postmitotic Purkinje neurons requires pRb family member function. Mol. Cell. Neurosci. 6, 153–167 (1995).
  Article CAS PubMed Google Scholar
• Feddersen, R. M., Ehlenfeldt, R., Yunis, W. S., Clark, H. B. & Orr, H. T. Disrupted cerebellar cortical development and progressive degeneration of Purkinje cells in SV40 T antigen transgenic mice. Neuron 9, 955–966 (1992). The earliest demonstration (see also references 44 and 46) that driving a cell cycle in a postmitotic neuron triggers death rather than division.
  Article CAS PubMed Google Scholar
• Feddersen, R. M. et al. Susceptibility to cell death induced by mutant SV40 T-antigen correlates with Purkinje neuron functional development. Mol. Cell. Neurosci. 9, 42–62 (1997).
  Article CAS PubMed Google Scholar
• Athanasiou, M. C. et al. The transcription factor E2F-1 in SV40 T antigen-induced cerebellar Purkinje cell degeneration. Mol. Cell. Neurosci. 12, 16–28 (1998).
  Article CAS PubMed Google Scholar
• Macleod, K. F., Hu, Y. & Jacks, T. Loss of Rb activates both p53-dependent and independent cell death pathways in the developing mouse nervous system. EMBO J. 15, 6178–6188 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Tsai, K. Y. et al. Mutation of E2f-1 suppresses apoptosis and inappropriate S phase entry and extends survival of Rb-deficient mouse embryos. Mol. Cell 2, 293–304 (1998).
  Article CAS PubMed Google Scholar
• Freeman, R. S., Estus, S. & Johnson, E. M. Jr. Analysis of cell cycle-related gene expression in postmitotic neurons: selective induction of Cyclin D1 during programmed cell death. Neuron 12, 343–355 (1994).
  Article CAS PubMed Google Scholar
• Herrup, K. & Busser, J. C. The induction of multiple cell cycle events precedes target-related neuronal death. Development 121, 2385–2395 (1995). The first demonstration that natural examples of developmental cell death are preceded by cell cycle activation.
  Article CAS PubMed Google Scholar
• Farinelli, S. E. & Greene, L. A. Cell cycle blockers mimosine, ciclopirox, and deferoxamine prevent the death of PC12 cells and postmitotic sympathetic neurons after removal of trophic support. J. Neurosci. 16, 1150–1162 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Park, D. S., Levine, B., Ferrari, G. & Greene, L. A. Cyclin dependent kinase inhibitors and dominant negative cyclin dependent kinase 4 and 6 promote survival of NGF-deprived sympathetic neurons. J. Neurosci. 17, 8975–8983 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Park, D. S., Morris, E. J., Greene, L. A. & Geller, H. M. G1/S cell cycle blockers and inhibitors of cyclin-dependent kinases suppress camptothecin-induced neuronal apoptosis. J. Neurosci. 17, 1256–1270 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Park, D. S., Farinelli, S. E. & Greene, L. A. Inhibitors of cyclin-dependent kinases promote survival of post-mitotic neuronally differentiated PC12 cells and sympathetic neurons. J. Biol. Chem. 271, 8161–8169 (1996).
  Article PubMed Google Scholar
• Ferrari, G. & Greene, L. A. Proliferative inhibition by dominant-negative Ras rescues naive and neuronally differentiated PC12 cells from apoptotic death. EMBO J. 13, 5922–5928 (1994).
  Article CAS PubMed PubMed Central Google Scholar
• Park, D. S., Obeidat, A., Giovanni, A. & Greene, L. A. Cell cycle regulators in neuronal death evoked by excitotoxic stress: implications for neurodegeneration and its treatment. Neurobiol. Aging 21, 771–781 (2000).
  Article CAS PubMed Google Scholar
• Courtney, M. J. & Coffey, E. T. The mechanism of Ara-C-induced apoptosis of differentiating cerebellar granule neurons. Eur. J. Neurosci. 11, 1073–1084 (1999).
  Article CAS PubMed Google Scholar
• Mirjany, M., Ho, L. & Pasinetti, G. M. Role of cyclooxygenase-2 in neuronal cell cycle activity and glutamate-mediated excitotoxicity. J. Pharmacol. Exp. Ther. 301, 494–500 (2002).
  Article CAS PubMed Google Scholar
• Padmanabhan, J., Park, D. S., Greene, L. A. & Shelanski, M. L. Role of cell cycle regulatory proteins in cerebellar granule neuron apoptosis. J. Neurosci. 19, 8747–8756 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Liu, D. X., Biswas, S. C. & Greene, L. A. B-myb and C-myb play required roles in neuronal apoptosis evoked by nerve growth factor deprivation and DNA damage. J. Neurosci. 24, 8720–8725 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Biswas, S. C., Liu, D. X. & Greene, L. A. Bim is a direct target of a neuronal E2F-dependent apoptotic pathway. J. Neurosci. 25, 8349–8358 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Konishi, Y. & Bonni, A. The E2F-Cdc2 cell-cycle pathway specifically mediates activity deprivation-induced apoptosis of postmitotic neurons. J. Neurosci. 23, 1649–1658 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Konishi, Y., Lehtinen, M., Donovan, N. & Bonni, A. Cdc2 phosphorylation of BAD links the cell cycle to the cell death machinery. Mol. Cell 9, 1005–1016 (2002).
  Article CAS PubMed Google Scholar
• Lipinski, M. M. et al. Cell-autonomous and non-cell-autonomous functions of the Rb tumor suppressor in developing central nervous system. EMBO J. 20, 3402–3413 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Maandag, E. C. et al. Developmental rescue of an embryonic-lethal mutation in the retinoblastoma gene in chimeric mice. EMBO J. 13, 4260–4268 (1994).
  Article CAS PubMed PubMed Central Google Scholar
• Williams, B. O. et al. Extensive contribution of Rb-deficient cells to adult chimeric mice with limited histopathological consequences. EMBO J. 13, 4251–4259 (1994).
  Article CAS PubMed PubMed Central Google Scholar
• MacPherson, D. et al. Conditional mutation of Rb causes cell cycle defects without apoptosis in the central nervous system. Mol. Cell Biol. 23, 1044–1053 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Wu, L. et al. Extra-embryonic function of Rb is essential for embryonic development and viability. Nature 421, 942–947 (2003).
  Article CAS PubMed Google Scholar
• De Bruin, A. et al. Rb function in extraembryonic lineages suppresses apoptosis in the CNS of Rb-deficient mice. Proc. Natl Acad. Sci. USA 100, 6546–6551 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Vincent, I., Rosado, M. & Davies, P. Mitotic mechanisms in Alzheimer's disease? J. Cell Biol. 132, 413–425 (1996).
  Article CAS PubMed Google Scholar
• Vincent, I., Zheng, J. H., Dickson, D. W., Kress, Y. & Davies, P. Mitotic phosphoepitopes precede paired helical filaments in Alzheimer's disease. Neurobiol. Aging 19, 287–296 (1998).
  Article CAS PubMed Google Scholar
• Nagy, Z., Esiri, M., Cato, A. & Smith, A. Cell cycle markers in the hippocampus in Alzheimer's disease. Acta Neuropathol. (Berl) 94, 6–15 (1997).
  Article CAS Google Scholar
• Busser, J., Geldmacher, D. S. & Herrup, K. Ectopic cell cycle proteins predict the sites of neuronal cell death in Alzheimer's disease brain. J. Neurosci. 18, 2801–2807 (1998). The first demonstration that cell cycle events in human neurodegenerative disease are accompanied by DNA replication.
  Article CAS PubMed PubMed Central Google Scholar
• Yang, Y., Geldmacher, D. S. & Herrup, K. DNA replication precedes neuronal cell death in Alzheimer's disease. J. Neurosci. 21, 2661–2668 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Yang, Y., Mufson, E. J. & Herrup, K. Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer's disease. J. Neurosci. 23, 2557–2563 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Arendt, T., Holzer, M. & Gartner, U. Neuronal expression of cycline dependent kinase inhibitors of the INK4 family in Alzheimer's disease. J. Neural Transm. 105, 949–960 (1998).
  Article CAS PubMed Google Scholar
• Hoozemans, J. J. et al. Cyclin D1 and cyclin E are co-localized with cyclo-oxygenase 2 (COX-2) in pyramidal neurons in Alzheimer disease temporal cortex. J. Neuropathol. Exp. Neurol. 61, 678–688 (2002).
  Article CAS PubMed Google Scholar
• McShea, A., Harris, P. L., Webster, K. R., Wahl, A. F. & Smith, M. A. Abnormal expression of the cell cycle regulators P16 and CDK4 in Alzheimer's disease. Am. J. Pathol. 150, 1933–1939 (1997).
  CAS PubMed PubMed Central Google Scholar
• Vincent, I., Jicha, G., Rosado, M. & Dickson, D. W. Aberrant expression of mitotic cdc2/cyclin B1 kinase in degenerating neurons of Alzheimer's disease brain. J. Neurosci. 17, 3588–3598 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Smith, M. Z., Nagy, Z. & Esiri, M. M. Cell cycle-related protein expression in vascular dementia and Alzheimer's disease. Neurosci. Lett. 271, 45–48 (1999).
  Article CAS PubMed Google Scholar
• Arendt, T., Rodel, L., Gartner, U. & Holzer, M. Expression of the cyclin-dependent kinase inhibitor p16 in Alzheimer's disease. Neuroreport 7, 3047–3049 (1996).
  Article CAS PubMed Google Scholar
• Zhu, X. et al. Elevated expression of a regulator of the G2/M phase of the cell cycle, neuronal CIP-1-associated regulator of cyclin B, in Alzheimer's disease. J. Neurosci. Res. 75, 698–703 (2004).
  Article CAS PubMed Google Scholar
• Johansson, A. et al. Genetic association of CDC2 with cerebrospinal fluid tau in Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 20, 367–374 (2005).
  Article CAS PubMed Google Scholar
• Johansson, A. et al. Increased frequency of a new polymorphism in the cell division cycle 2 (cdc2) gene in patients with Alzheimer's disease and frontotemporal dementia. Neurosci. Lett. 340, 69–73 (2003).
  Article CAS PubMed Google Scholar
• Nguyen, M. D. et al. Cell cycle regulators in the neuronal death pathway of amyotrophic lateral sclerosis caused by mutant superoxide dismutase 1. J. Neurosci. 23, 2131–2140 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Ranganathan, S. & Bowser, R. Alterations in G1 to S phase cell-cycle regulators during amyotrophic lateral sclerosis. Am. J. Pathol. 162, 823–835 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Ranganathan, S., Scudiere, S. & Bowser, R. Hyperphosphorylation of the retinoblastoma gene product and altered subcellular distribution of E2F-1 during Alzheimer's disease and amyotrophic lateral sclerosis. J. Alzheimers Dis. 3, 377–385 (2001).
  Article CAS PubMed Google Scholar
• Yang, Y. & Herrup, K. Loss of neuronal cell cycle control in ataxia-telangiectasia: a unified disease mechanism. J. Neurosci. 25, 2522–2529 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Burns, K. A. et al. Nestin-CreER mice reveal DNA synthesis by nonapoptotic neurons following cerebral ischemia-hypoxia. Cereb. Cortex 27 Jan 2007 (doi:10.1093/cercor/bhl164).
  Article PubMed Google Scholar
• Höglinger, G. et al. The pRb/E2F cell-cycle pathway mediates cell death in Parkinson's disease. Proc. Natl Acad. Sci. USA 104, 3585–3590 (2007).
  Article PubMed PubMed Central CAS Google Scholar
• Jordan-Sciutto, K. L., Dorsey, R., Chalovich, E. M., Hammond, R. R. & Achim, C. L. Expression patterns of retinoblastoma protein in Parkinson disease. J. Neuropathol. Exp. Neurol. 62, 68–74 (2003).
  Article CAS PubMed Google Scholar
• West, A. B., Dawson, V. L. & Dawson, T. M. To die or grow: Parkinson's disease and cancer. Trends Neurosci. 28, 348–352 (2005).
  Article CAS PubMed Google Scholar
• Love, S. Neuronal expression of cell cycle-related proteins after brain ischaemia in man. Neurosci. Lett. 353, 29–32 (2003).
  Article CAS PubMed Google Scholar
• Jordan-Sciutto, K. L., Wang, G., Murphey-Corb, M. & Wiley, C. A. Cell cycle proteins exhibit altered expression patterns in lentiviral-associated encephalitis. J. Neurosci. 22, 2185–2195 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Jordan-Sciutto, K. L., Wang, G., Murphy-Corb, M. & Wiley, C. A. Induction of cell-cycle regulators in simian immunodeficiency virus encephalitis. Am. J. Pathol. 157, 497–507 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Barlow, C. et al. Atm-deficient mice: a paradigm of ataxia telangiectasia. Cell 86, 159–171 (1996).
  Article CAS PubMed Google Scholar
• Borghesani, P. R. et al. Abnormal development of Purkinje cells and lymphocytes in Atm mutant mice. Proc. Natl Acad. Sci. USA 97, 3336–3341 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Xu, Y. et al. Targeted disruption of ATM leads to growth retardation, chromosomal fragmentation during meiosis, immune defects, and thymic lymphoma. Genes Dev. 10, 2411–2422 (1996).
  Article CAS PubMed Google Scholar
• Lamb, B. T. et al. Introduction and expression of the 400 kilobase amyloid precursor protein gene in transgenic mice. Nature Genet. 5, 22–30 (1993).
  Article CAS PubMed Google Scholar
• Hsiao, K. K. et al. Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins. Neuron 15, 1203–1218 (1995).
  Article CAS PubMed Google Scholar
• Hsiao, K. et al. Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science 274, 99–102 (1996).
  Article CAS PubMed Google Scholar
• Games, D. et al. Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein. Nature 373, 523–527 (1995).
  Article CAS PubMed Google Scholar
• Sturchler-Pierrat, C. et al. Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc. Natl Acad. Sci. USA 94, 13287–13292 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Mucke, L. et al. High-level neuronal expression of aβ 1–42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J. Neurosci. 20, 4050–4058 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Citron, M. et al. Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid β-protein in both transfected cells and transgenic mice. Nature Med. 3, 67–72 (1997).
  Article CAS PubMed Google Scholar
• Calhoun, M. E. et al. Neuron loss in APP transgenic mice. Nature 395, 755–756 (1998).
  Article CAS PubMed Google Scholar
• Barlow, C. et al. ATM is a cytoplasmic protein in mouse brain required to prevent lysosomal accumulation. Proc. Natl Acad. Sci. USA 97, 871–876 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Hock, B. J. Jr. & Lamb, B. T. Transgenic mouse models of Alzheimer's disease. Trends Genet. 17, S7–S12 (2001).
  Article CAS PubMed Google Scholar
• Yang, Y., Varvel, N. H., Lamb, B. T. & Herrup, K. Ectopic cell cycle events link human Alzheimer's disease and amyloid precursor protein transgenic mouse models. J. Neurosci. 26, 775–784 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Gartner, U. et al. Amyloid deposition in APP23 mice is associated with the expression of cyclins in astrocytes but not in neurons. Acta Neuropathol. (Berl) 106, 535–544 (2003).
  Article CAS Google Scholar
• Jordan-Sciutto, K., Rhodes, J. & Bowser, R. Altered subcellular distribution of transcriptional regulators in response to Aβ peptide and during Alzheimer's disease. Mech. Ageing Dev. 123, 11–20 (2001).
  Article CAS PubMed Google Scholar
• Jordan-Sciutto, K. L., Murray Fenner, B. A., Wiley, C. A. & Achim, C. L. Response of cell cycle proteins to neurotrophic factor and chemokine stimulation in human neuroglia. Exp. Neurol. 167, 205–214 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Strachan, G. D., Kopp, A. S., Koike, M. A., Morgan, K. L. & Jordan-Sciutto, K. L. Chemokine- and neurotrophic factor-induced changes in E2F1 localization and phosphorylation of the retinoblastoma susceptibility gene product (pRb) occur by distinct mechanisms in murine cortical cultures. Exp. Neurol. 193, 455–468 (2005).
  Article CAS PubMed Google Scholar
• Delalle, I., Takahashi, T., Nowakowski, R. S., Tsai, L. H. & Caviness, V. S. Jr. Cyclin E-p27 opposition and regulation of the G1 phase of the cell cycle in the murine neocortical PVE: a quantitative analysis of mRNA in situ hybridization. Cereb. Cortex 9, 824–832 (1999). A detailed look at the effects on cell cycle kinetics of the elimination of a key CDK inhibitor, p27.
  Article CAS PubMed Google Scholar
• Dyer, M. A. & Cepko, C. L. p27Kip1 and p57Kip2 regulate proliferation in distinct retinal progenitor cell populations. J. Neurosci. 21, 4259–4271 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Dyer, M. A. & Cepko, C. L. p57Kip2 regulates progenitor cell proliferation and amacrine interneuron development in the mouse retina. Development 127, 3593–3605 (2000).
  Article CAS PubMed Google Scholar
• Gui, H., Li, S. & Matise, M. P. A cell-autonomous requirement for Cip/Kip cyclin-kinase inhibitors in regulating neuronal cell cycle exit but not differentiation in the developing spinal cord. Dev. Biol. 301, 14–26 (2007).
  Article CAS PubMed Google Scholar
• Nguyen, L. et al. p27kip1 independently promotes neuronal differentiation and migration in the cerebral cortex. Genes Dev. 20, 1511–1524 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Cicero, S. & Herrup, K. Cyclin-dependent kinase 5 is essential for neuronal cell cycle arrest and differentiation. J. Neurosci. 25, 9658–9668 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Rosales, J. L., Nodwell, M. J., Johnston, R. N. & Lee, K. Y. Cdk5/p25nck5a interaction with synaptic proteins in bovine brain. J. Cell Biochem. 78, 151–159 (2000).
  Article CAS PubMed Google Scholar
• Fu, A. K. et al. Cdk5 is involved in neuregulin-induced AChR expression at the neuromuscular junction. Nature Neurosci. 4, 374–381 (2001).
  Article CAS PubMed Google Scholar
• Fu, A. K. et al. Aberrant motor axon projection, acetylcholine receptor clustering, and neurotransmission in cyclin-dependent kinase 5 null mice. Proc. Natl Acad. Sci. USA 102, 15224–15229 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Fu, W. Y. et al. Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism. Nature Neurosci. 10, 67–76 (2007).
  Article CAS PubMed Google Scholar
• Lee, S. Y., Wenk, M. R., Kim, Y., Nairn, A. C. & De Camilli, P. Regulation of synaptojanin 1 by cyclin-dependent kinase 5 at synapses. Proc. Natl Acad. Sci. USA 101, 546–551 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Morabito, M. A., Sheng, M. & Tsai, L. H. Cyclin-dependent kinase 5 phosphorylates the N-terminal domain of the postsynaptic density protein PSD-95 in neurons. J. Neurosci. 24, 865–876 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Tomizawa, K. et al. Cophosphorylation of amphiphysin I and dynamin I by Cdk5 regulates clathrin-mediated endocytosis of synaptic vesicles. J. Cell Biol. 163, 813–824 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Huang, Z., Zang, K. & Reichardt, L. F. The origin recognition core complex regulates dendrite and spine development in postmitotic neurons. J. Cell Biol. 170, 527–535 (2005). Analysis of the unexplained presence of proteins normally associated with DNA replication biochemistry in the mature neuronal synapse.
  Article CAS PubMed PubMed Central Google Scholar
• Thome, K. C. et al. Subsets of human origin recognition complex (ORC) subunits are expressed in non-proliferating cells and associate with non-ORC proteins. J. Biol. Chem. 275, 35233–35241 (2000).
  Article CAS PubMed Google Scholar
• Buss, R. R. & Oppenheim, R. W. Role of programmed cell death in normal neuronal development and function. Anat. Sci. Int. 79, 191–197 (2004).
  Article PubMed Google Scholar
• Perez-Garijo, A., Martin, F. A. & Morata, G. Caspase inhibition during apoptosis causes abnormal signalling and developmental aberrations in Drosophila. Development 131, 5591–5598 (2004). 'Undead' cells signal with mitogens to neighbouring cells; the authors take a first pass at identifying the signalling molecules involved.
  Article CAS PubMed Google Scholar
• Perez-Garijo, A., Martin, F. A., Struhl, G. & Morata, G. Dpp signaling and the induction of neoplastic tumors by caspase-inhibited apoptotic cells in Drosophila. Proc. Natl Acad. Sci. USA 102, 17664–17669 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Huh, J. R., Guo, M. & Hay, B. A. Compensatory proliferation induced by cell death in the Drosophila wing disc requires activity of the apical cell death caspase Dronc in a nonapoptotic role. Curr. Biol. 14, 1262–1266 (2004).
  Article CAS PubMed Google Scholar
• Field, S. J. et al. E2F-1 functions in mice to promote apoptosis and suppress proliferation. Cell 85, 549–561 (1996).
  Article CAS PubMed Google Scholar
• Yamasaki, L. et al. Tumor induction and tissue atrophy in mice lacking E2F-1. Cell 85, 537–548 (1996).
  Article CAS PubMed Google Scholar
• McKinnon, P. J. ATM and ataxia telangiectasia. EMBO Rep. 5, 772–776 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Shiloh, Y. & Kastan, M. B. ATM: genome stability, neuronal development, and cancer cross paths. Adv. Cancer Res. 83, 209–254 (2001).
  Article CAS PubMed Google Scholar
• Kastan, M. B. & Lim, D. S. The many substrates and functions of ATM. Nature Rev. Mol. Cell Biol. 1, 179–186 (2000).
  Article CAS Google Scholar
• Gilmore, E. C., Ohshima, T., Goffinet, A. M., Kulkarni, A. B. & Herrup, K. Cyclin-dependent kinase 5-deficient mice demonstrate novel developmental arrest in cerebral cortex. J. Neurosci. 18, 6370–6377 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Ohshima, T. et al. Migration defects of _cdk5_−/− neurons in the developing cerebellum is cell autonomous. J. Neurosci. 19, 6017–6026 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Ohshima, T. et al. Targeted disruption of the cyclin-dependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death. Proc. Natl Acad. Sci. USA 93, 11173–11178 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• O'Hare, M. J. et al. Differential roles of nuclear and cytoplasmic cyclin-dependent kinase 5 in apoptotic and excitotoxic neuronal death. J. Neurosci. 25, 8954–8966 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Fantl, V., Stamp, G., Andrews, A., Rosewell, I. & Dickson, C. Mice lacking cyclin D1 are small and show defects in eye and mammary gland development. Genes Dev. 9, 2364–2372 (1995).
  Article CAS PubMed Google Scholar
• Sicinski, P. et al. Cyclin D1 provides a link between development and oncogenesis in the retina and breast. Cell 82, 621–630 (1995).
  Article CAS PubMed Google Scholar
• Sicinski, P. et al. Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis. Nature 384, 470–474 (1996).
  Article CAS PubMed Google Scholar
• Huard, J. M., Forster, C. C., Carter, M. L., Sicinski, P. & Ross, M. E. Cerebellar histogenesis is disturbed in mice lacking cyclin D2. Development 126, 1927–1935 (1999).
  Article CAS PubMed Google Scholar
• Georgia, S. & Bhushan, A. β cell replication is the primary mechanism for maintaining postnatal β cell mass. J. Clin. Invest. 114, 963–968 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Ciemerych, M. A. et al. Development of mice expressing a single D-type cyclin. Genes Dev. 16, 3277–3289 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Lee, M. H. et al. Targeted disruption of p107: functional overlap between p107 and Rb. Genes Dev. 10, 1621–1632 (1996).
  Article CAS PubMed Google Scholar
• Eilam, R. et al. Selective loss of dopaminergic nigro-striatal neurons in brains of Atm-deficient mice. Proc. Natl Acad. Sci. USA 95, 12653–12656 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Brown, E. J. & Baltimore, D. ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes Dev. 14, 397–402 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Liu, Q. et al. Chk1 is an essential kinase that is regulated by Atr and required for the G2/M DNA damage checkpoint. Genes Dev. 14, 1448–1459 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Takai, H. et al. Chk2-deficient mice exhibit radioresistance and defective p53-mediated transcription. EMBO J. 21, 5195–5205 (2002).
  Article CAS PubMed PubMed Central Google Scholar