Generation of neuronal variability and complexity

Listen to an interview with Fred Gage on the stem cells podcast The production of specialized differentiated neurons derived from stem cells has been proposed as a revolutionary technology for regenerative medicine. However, few examples of specific neuronal cell differentiation have been described so far. Although stem-cell tissue replacement might be seemingly straightforward in other cases, the high degree of complexity of the nervous system raises the challenge of tissue replacement substantially. Understanding mechanisms of neuronal diversification will not only be relevant for therapeutic purposes but might also shed light on the differences in cognitive abilities, personality traits and psychiatric conditions observed in humans.

[1]  N. Okada,et al.  LINEs Mobilize SINEs in the Eel through a Shared 3′ Sequence , 2002, Cell.

[2]  C. Meischl,et al.  A new exon created by intronic insertion of a rearranged LINE-1 element as the cause of chronic granulomatous disease , 2000, European Journal of Human Genetics.

[3]  J. V. Moran,et al.  Initial sequencing and analysis of the human genome. , 2001, Nature.

[4]  B. Pakkenberg,et al.  Aging and the human neocortex , 2003, Experimental Gerontology.

[5]  A. C. Collins,et al.  The Role of RNA Editing of Kainate Receptors in Synaptic Plasticity and Seizures , 2001, Neuron.

[6]  J. Chun,et al.  Chromosome Segregation Defects Contribute to Aneuploidy in Normal Neural Progenitor Cells , 2003, The Journal of Neuroscience.

[7]  M. Ogasawara,et al.  Embryonic karyotype of abortuses in relation to the number of previous miscarriages. , 2000, Fertility and sterility.

[8]  R. Yolken,et al.  Identification of differentially expressed RNA transcripts in neuropsychiatric disorders , 1997, Biological Psychiatry.

[9]  F. Papavasiliou,et al.  V(D)J Recombination and the Evolution of the Adaptive Immune System , 2003, PLoS biology.

[10]  Maro G. Machizawa,et al.  Neural activity predicts individual differences in visual working memory capacity , 2004, Nature.

[11]  P. Mombaerts,et al.  Odorant receptor gene choice is reset by nuclear transfer from mouse olfactory sensory neurons , 2004, Nature.

[12]  Hongjun Song,et al.  Neurogenesis in the adult brain: new strategies for central nervous system diseases. , 2004, Annual review of pharmacology and toxicology.

[13]  R. Dingledine,et al.  Genetic regulation of glutamate receptor ion channels. , 1999, Annual review of pharmacology and toxicology.

[14]  Jef D. Boeke,et al.  Human L1 Retrotransposition: cisPreference versus trans Complementation , 2001, Molecular and Cellular Biology.

[15]  C. Fuller,et al.  Fluorescence In Situ Hybridization (FISH) in Diagnostic and Investigative Neuropathology , 2002, Brain pathology.

[16]  R. Dingledine,et al.  The glutamate receptor ion channels. , 1999, Pharmacological reviews.

[17]  J. C. Clemens,et al.  Drosophila Dscam Is an Axon Guidance Receptor Exhibiting Extraordinary Molecular Diversity , 2000, Cell.

[18]  Y. Kawahara,et al.  Deficient RNA editing of GluR2 and neuronal death in amyotropic lateral sclerosis , 2005, Journal of Molecular Medicine.

[19]  H. Meijer,et al.  Mechanisms of translational control by the 3' UTR in development and differentiation. , 2005, Seminars in cell & developmental biology.

[20]  Bosiljka Tasic,et al.  Alternative pre-mRNA splicing and proteome expansion in metazoans , 2002, Nature.

[21]  J. T. Kadonaga,et al.  The RNA polymerase II core promoter. , 2003, Annual review of biochemistry.

[22]  M. Götz,et al.  Cortical development: the art of generating cell diversity , 2005, Development.

[23]  M. Gellert,et al.  The taming of a transposon: V(D)J recombination and the immune system , 2004, Immunological reviews.

[24]  P. Deininger,et al.  LINE-1 RNA splicing and influences on mammalian gene expression , 2006, Nucleic acids research.

[25]  J Schröder,et al.  Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[26]  R. Reenan,et al.  A-to-I Pre-mRNA Editing in Drosophila Is Primarily Involved in Adult Nervous System Function and Integrity , 2000, Cell.

[27]  A. Multani,et al.  Aneuploidy, stem cells and cancer. , 2006, EXS.

[28]  T. Ayoubi,et al.  Regulation of gene expression by alternative promoters , 1996, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[29]  J. Chun,et al.  Aneuploid neurons are functionally active and integrated into brain circuitry , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[30]  B L Finlay,et al.  Local differences in the amount of early cell death in neocortex predict adult local specializations. , 1983, Science.

[31]  E. Soriano,et al.  Cell death and removal in the cerebral cortex during development , 1992, Progress in Neurobiology.

[32]  R. Duvoisin,et al.  Alternative Splicing Unmasks Dendritic and Axonal Targeting Signals in Metabotropic Glutamate Receptor 1 , 2002, The Journal of Neuroscience.

[33]  H. Kazazian Mobile Elements: Drivers of Genome Evolution , 2004, Science.

[34]  Tom Maniatis,et al.  Promoter Choice Determines Splice Site Selection in Protocadherin α and γ Pre-mRNA Splicing , 2002 .

[35]  D. Black,et al.  Alternative RNA splicing in the nervous system , 2001, Progress in Neurobiology.

[36]  E. Arenas,et al.  Differential usage of multiple brain-derived neurotrophic factor promoters in the rat brain following neuronal activation. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[37]  M. O’Connell,et al.  Survival Is Impossible Without an Editor , 2000, Science.

[38]  P. Deininger,et al.  Human retroelements may introduce intragenic polyadenylation signals , 2005, Cytogenetic and Genome Research.

[39]  Victoria Arango,et al.  Altered Editing of Serotonin 2C Receptor Pre-mRNA in the Prefrontal Cortex of Depressed Suicide Victims , 2002, Neuron.

[40]  Steven W. Flavell,et al.  Activity-Dependent Regulation of MEF2 Transcription Factors Suppresses Excitatory Synapse Number , 2006, Science.

[41]  Lisa M. D'Souza,et al.  Genome sequence of the Brown Norway rat yields insights into mammalian evolution , 2004, Nature.

[42]  B. Bass,et al.  RNA editing by ADARs is important for normal behavior in Caenorhabditis elegans , 2002, The EMBO journal.

[43]  Thierry Heidmann,et al.  LINE-mediated retrotransposition of marked Alu sequences , 2003, Nature Genetics.

[44]  E. Jones,et al.  Histone methylation at gene promoters is associated with developmental regulation and region‐specific expression of ionotropic and metabotropic glutamate receptors in human brain , 2005, Journal of neurochemistry.

[45]  R. Yolken,et al.  Epigenetic studies of genomic retroelements in major psychosis , 2004, Schizophrenia Research.

[46]  T. Crow,et al.  Isolation and phylogeny of endogenous retrovirus sequences belonging to the HERV-W family in primates. , 1999, The Journal of general virology.

[47]  Kenneth S. Kosik,et al.  The Elegance of the MicroRNAs: A Neuronal Perspective , 2005, Neuron.

[48]  P. Grabowski,et al.  Cell- and stage-specific splicing events resolved in specialized neurons of the rat cerebellum. , 1996, RNA.

[49]  Kevin Eggan,et al.  Mice cloned from olfactory sensory neurons , 2004, Nature.

[50]  D. Bartel MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[51]  Fred H. Gage,et al.  The Adult Rat Hippocampus Contains Primordial Neural Stem Cells , 1997, Molecular and Cellular Neuroscience.

[52]  D. Black Mechanisms of alternative pre-messenger RNA splicing. , 2003, Annual review of biochemistry.

[53]  Kazunari Taira,et al.  A Small Modulatory dsRNA Specifies the Fate of Adult Neural Stem Cells , 2004, Cell.

[54]  Danny Reinberg,et al.  Histone lysine methylation: a signature for chromatin function. , 2003, Trends in genetics : TIG.

[55]  F. Gage,et al.  Mammalian neural stem cells. , 2000, Science.

[56]  I. Gottesman,et al.  Human development: biological and genetic processes. , 2005, Annual review of psychology.

[57]  A. Vezzani,et al.  Alternative Splicing at the C‐terminal but not at the N‐terminal Domain of the NMDA Receptor NR1 is Altered in the Kindled Hippocampus , 1995, The European journal of neuroscience.

[58]  B. Bass,et al.  Inosine exists in mRNA at tissue‐specific levels and is most abundant in brain mRNA , 1998, The EMBO journal.

[59]  T. Maniatis,et al.  A Striking Organization of a Large Family of Human Neural Cadherin-like Cell Adhesion Genes , 1999, Cell.

[60]  Gene W. Yeo,et al.  Noncoding RNAs in the mammalian central nervous system. , 2006, Annual review of neuroscience.

[61]  Haibo Zhang,et al.  Biased alternative polyadenylation in human tissues , 2005, Genome Biology.

[62]  Juan I. Young,et al.  Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[63]  John Bracht,et al.  MicroRNAs: a developing story. , 2005, Current opinion in genetics & development.

[64]  J. B. Angevine Time of neuron origin in the diencephalon of the mouse. An autoradiographic study , 1970, The Journal of comparative neurology.

[65]  Colleen M. Niswender,et al.  RNA Editing of the Human Serotonin 5-Hydroxytryptamine 2C Receptor Silences Constitutive Activity* , 1999, The Journal of Biological Chemistry.

[66]  R. Oppenheim Cell death during development of the nervous system. , 1991, Annual review of neuroscience.

[67]  J. V. Moran,et al.  Multiple Fates of L1 Retrotransposition Intermediates in Cultured Human Cells , 2005, Molecular and Cellular Biology.

[68]  R. Williams,et al.  Mapping genes that modulate mouse brain development: a quantitative genetic approach. , 2000, Results and problems in cell differentiation.

[69]  P. Kincade A Developing Story , 2001, Cell.

[70]  Lin Lu,et al.  Rodent BDNF genes, novel promoters, novel splice variants, and regulation by cocaine , 2006, Brain Research.

[71]  Colin N. Dewey,et al.  Initial sequencing and comparative analysis of the mouse genome. , 2002 .

[72]  F. Alt,et al.  A Critical Role for DNA End-Joining Proteins in Both Lymphogenesis and Neurogenesis , 1998, Cell.

[73]  F. Gage,et al.  Adult neurogenesis and neural stem cells of the central nervous system in mammals , 2002, Journal of neuroscience research.

[74]  M. Tsuda,et al.  Differential Activation of Brain-derived Neurotrophic Factor Gene Promoters I and III by Ca2+ Signals Evoked vial-type Voltage-dependent andN-Methyl-d-aspartate Receptor Ca2+Channels* , 2000, The Journal of Biological Chemistry.

[75]  Y. Yung,et al.  Constitutional Aneuploidy in the Normal Human Brain , 2005, The Journal of Neuroscience.

[76]  H. Sakano,et al.  Detection of somatic DNA recombination in the transgenic mouse brain. , 1991, Science.

[77]  P. Tam,et al.  Distinct expression profiles of Mecp2 transcripts with different lengths of 3'UTR in the brain and visceral organs during mouse development. , 2005, Genomics.

[78]  T. Südhof,et al.  Neurexins: three genes and 1001 products. , 1998, Trends in genetics : TIG.

[79]  S. Grant,et al.  The synapse proteome and phosphoproteome: a new paradigm for synapse biology. , 2006, Biochemical Society transactions.

[80]  Alexandros D. Polydorides,et al.  The splice of life: Alternative splicing and neurological disease , 2001, Nature Reviews Neuroscience.

[81]  C Koch,et al.  Complexity and the nervous system. , 1999, Science.

[82]  R. Hehlmann,et al.  Human Endogenous Retrovirus Expression Profiles in Samples from Brains of Patients with Schizophrenia and Bipolar Disorders , 2005, Journal of Virology.

[83]  S. Mango,et al.  Regulation of Organogenesis by the Caenorhabditis elegans FoxA Protein PHA-4 , 2002, Science.

[84]  S. Tonegawa,et al.  On somatic recombination in the central nervous system of transgenic mice. , 1992, Science.

[85]  J. LaSalle,et al.  Elevated methyl-CpG-binding protein 2 expression is acquired during postnatal human brain development and is correlated with alternative polyadenylation , 2002, Journal of Molecular Medicine.

[86]  Colleen M Niswender,et al.  RNA Editing of the Human Serotonin 5-HT2C Receptor: Alterations in Suicide and Implications for Serotonergic Pharmacotherapy , 2001, Neuropsychopharmacology.

[87]  J. Harper,et al.  A Calcium-Regulated MEF2 Sumoylation Switch Controls Postsynaptic Differentiation , 2006, Science.

[88]  M. O’Connell,et al.  The many roles of an RNA editor , 2001, Nature Reviews Genetics.

[89]  Fred H. Gage,et al.  Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition , 2005, Nature.

[90]  E. Alleva,et al.  Epigenetic control of neurobehavioural plasticity: the role of neurotrophins , 2004, Behavioural pharmacology.

[91]  Thierry Heidmann,et al.  Human LINE retrotransposons generate processed pseudogenes , 2000, Nature Genetics.

[92]  M. Hübener,et al.  Activity‐dependent regulation of alternative splicing patterns in the rat brain , 1999, The European journal of neuroscience.

[93]  Neil Burgess,et al.  Neural representations in human spatial memory , 2003, Trends in Cognitive Sciences.

[94]  G. Edwalds-Gilbert,et al.  Alternative poly(A) site selection in complex transcription units: means to an end? , 1997, Nucleic acids research.

[95]  Gene W. Yeo,et al.  Variation in alternative splicing across human tissues , 2004, Genome Biology.

[96]  S. Rehen,et al.  Chromosomal variation in neurons of the developing and adult mammalian nervous system , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[97]  S. Akbarian,et al.  Editing for an AMPA receptor subunit RNA in prefrontal cortex and striatum in Alzheimer's disease, Huntington's disease and schizophrenia , 1995, Brain Research.