Adolescent Mouse Takes on An Active Transcriptomic Expression During Postnatal Cerebral Development

Postnatal cerebral development is a complicated biological process precisely controlled by multiple genes. To understand the molecular mechanism of cerebral development, we compared dynamics of mouse cerebrum transcriptome through three developmental stages using high-throughput RNA-seq technique. Three libraries were generated from the mouse cerebrum at infancy, adolescence and adulthood, respectively. Consequently, 44,557,729 (infancy), 59,257,530 (adolescence) and 72,729,636 (adulthood) reads were produced, which were assembled into 15,344, 16,048 and 15,775 genes, respectively. We found that the overall gene expression level increased from infancy to adolescence and decreased later on upon reaching adulthood. The adolescence cerebrum has the most active gene expression, with expression of a large number of regulatory genes up-regulated and some crucial pathways activated. Transcription factor (TF) analysis suggested the similar dynamics as expression profiling, especially those TFs functioning in neurogenesis differentiation, oligodendrocyte lineage determination and circadian rhythm regulation. Moreover, our data revealed a drastic increase in myelin basic protein (MBP)-coding gene expression in adolescence and adulthood, suggesting that the brain myelin may be generated since mouse adolescence. In addition, differential gene expression analysis indicated the activation of rhythmic pathway, suggesting the function of rhythmic movement since adolescence; Furthermore, during infancy and adolescence periods, gene expression related to axon repulsion and attraction showed the opposite trends, indicating that axon repulsion was activated after birth, while axon attraction might be activated at the embryonic stage and declined during the postnatal development. Our results from the present study may shed light on the molecular mechanism underlying the postnatal development of the mammalian cerebrum.

[1]  Chiara Romualdi,et al.  IDEG6: a web tool for detection of differentially expressed genes in multiple tag sampling experiments. , 2003, Physiological genomics.

[2]  S. Ranade,et al.  Stem cell transcriptome profiling via massive-scale mRNA sequencing , 2008, Nature Methods.

[3]  Peng Cui,et al.  Hydroxyurea-induced global transcriptional suppression in mouse ES cells. , 2010, Carcinogenesis.

[4]  S. Grillner,et al.  Central generation of locomotion in the spinal dogfish , 1976, Brain Research.

[5]  Otto W. Witte,et al.  Adult and Embryonic GAD Transcripts Are Spatiotemporally Regulated during Postnatal Development in the Rat Brain , 2009, PloS one.

[6]  E. Haber,et al.  The Polymyositis-Scleroderma Autoantigen Interacts with the Helix-Loop-Helix Proteins E12 and E47* , 1997, The Journal of Biological Chemistry.

[7]  Heinz Bönisch,et al.  Knockout of the norepinephrine transporter and pharmacologically diverse antidepressants prevent behavioral and brain neurotrophin alterations in two chronic stress models of depression , 2009, Journal of neurochemistry.

[8]  Carmen Birchmeier,et al.  Neuregulin-1/ErbB Signaling Serves Distinct Functions in Myelination of the Peripheral and Central Nervous System , 2008, Neuron.

[9]  Arne Gericke,et al.  Regulation of the PTEN phosphatase. , 2006, Gene.

[10]  G. Schett,et al.  Abundance of platelet-derived growth factors (PDGFs), PDGF receptors and activation of mitogen-activated protein kinases in brain decline with age. , 1998, Brain research. Molecular brain research.

[11]  E. Huang,et al.  Neurotrophins: roles in neuronal development and function. , 2001, Annual review of neuroscience.

[12]  Irving L. Weissman,et al.  Pten, Tumorigenesis, and Stem Cell Self-Renewal , 2006, Cell.

[13]  Colleen Manitt,et al.  Netrin Participates in the Development of Retinotectal Synaptic Connectivity by Modulating Axon Arborization and Synapse Formation in the Developing Brain , 2009, The Journal of Neuroscience.

[14]  M. Poo,et al.  The cell biology of neuronal navigation , 2001, Nature Cell Biology.

[15]  S. Baker,et al.  PTEN signaling in brain: neuropathology and tumorigenesis , 2008, Oncogene.

[16]  Natalie G. Ahn,et al.  The MAP kinase cascade. Discovery of a new signal transduction pathway. , 1993 .

[17]  Manfred Gessler,et al.  Hey genes: a novel subfamily of hairy- and Enhancer of split related genes specifically expressed during mouse embryogenesis , 1999, Mechanisms of Development.

[18]  Chao Zhao,et al.  Myelin Impairs CNS Remyelination by Inhibiting Oligodendrocyte Precursor Cell Differentiation , 2006, The Journal of Neuroscience.

[19]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[20]  A. Buonanno,et al.  Regulation of ErbB-4 endocytosis by neuregulin in GABAergic hippocampal interneurons , 2007, Brain Research Bulletin.

[21]  David J Anderson,et al.  Identification of a Novel Family of Oligodendrocyte Lineage-Specific Basic Helix–Loop–Helix Transcription Factors , 2000, Neuron.

[22]  G. Almazan,et al.  Acetylcholine agonists stimulate mitogen‐activated protein kinase in oligodendrocyte progenitors by muscarinic receptors , 1997, Journal of neuroscience research.

[23]  Carmen Blanco-Aparicio,et al.  PTEN, more than the AKT pathway. , 2007, Carcinogenesis.

[24]  Emmanuel Dias-Neto,et al.  Discovery of a functional protein complex of netrin-4, laminin γ1 chain, and integrin α6β1 in mouse neural stem cells , 2009, Proceedings of the National Academy of Sciences.

[25]  Claudia S. Barros,et al.  Impaired maturation of dendritic spines without disorganization of cortical cell layers in mice lacking NRG1/ErbB signaling in the central nervous system , 2009, Proceedings of the National Academy of Sciences.

[26]  Julia T. Choi,et al.  Adaptation reveals independent control networks for human walking , 2007, Nature Neuroscience.

[27]  E. Mccleskey,et al.  Rap1 mediates sustained MAP kinase activation induced by nerve growth factor , 1998, Nature.

[28]  Simon Rosenfeld,et al.  Numerical Deconvolution of cDNA Microarray Signal: Simulation Study , 2004, Annals of the New York Academy of Sciences.

[29]  M. Liberman,et al.  Nonneuronal cells regulate synapse formation in the vestibular sensory epithelium via erbB-dependent BDNF expression , 2010, Proceedings of the National Academy of Sciences.

[30]  Minoru Tanaka,et al.  Positional Cloning of the Mouse Circadian Clock Gene , 1997, Cell.

[31]  O. Kiehn,et al.  Physiological, anatomical and genetic identification of CPG neurons in the developing mammalian spinal cord , 2003, Progress in Neurobiology.

[32]  Alex M. Henry,et al.  High-resolution gene expression atlases for adult and developing mouse brain and spinal cord , 2012, Mammalian Genome.

[33]  中尾 光輝,et al.  KEGG(Kyoto Encyclopedia of Genes and Genomes)〔和文〕 (特集 ゲノム医学の現在と未来--基礎と臨床) -- (データベース) , 2000 .

[34]  Q. Wan,et al.  Phosphatase PTEN in neuronal injury and brain disorders , 2007, Trends in Neurosciences.

[35]  H. Scharfman,et al.  Brain-derived neurotrophic factor transgenic mice exhibit passive avoidance deficits, increased seizure severity and in vitro hyperexcitability in the hippocampus and entorhinal cortex , 1999, Neuroscience.

[36]  Massimo Pasqualetti,et al.  Hox Paralog Group 2 Genes Control the Migration of Mouse Pontine Neurons through Slit-Robo Signaling , 2008, PLoS biology.

[37]  Ariel S. Schwartz,et al.  An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man , 2010, Cell.

[38]  Birgitta Lannering,et al.  Age‐dependent sensitivity of the developing brain to irradiation is correlated with the number and vulnerability of progenitor cells , 2005, Journal of neurochemistry.

[39]  David R Kaplan,et al.  Neurotrophin signal transduction in the nervous system , 2000, Current Opinion in Neurobiology.

[40]  Uwe Drescher,et al.  Slit and Netrin-1 guide cranial motor axon pathfinding via Rho-kinase, myosin light chain kinase and myosin II , 2010, Neural Development.

[41]  David J. Anderson,et al.  neurogenins,a Novel Family ofatonal-Related bHLH Transcription Factors, Are Putative Mammalian Neuronal Determination Genes That Reveal Progenitor Cell Heterogeneity in the Developing CNS and PNS , 1996, Molecular and Cellular Neuroscience.

[42]  E. Shooter,et al.  Apoptosis of Central and Peripheral Neurons Can Be Prevented with Cyclin‐Dependent Kinase/Mitogen‐Activated Protein Kinase Inhibitors , 1998, Journal of neurochemistry.

[43]  Jin Ming-shun.  Histology Research of Telencephalon Development of Kun Ming Mouse and β-APP Expression during its Fetal and Postnatal Development , 2009 .

[44]  Michael E. Greenberg,et al.  Opposing Effects of ERK and JNK-p38 MAP Kinases on Apoptosis , 1995, Science.

[45]  J. Chilton.  Molecular mechanisms of axon guidance. , 2006, Developmental biology.

[46]  Rafael A Irizarry,et al.  Exploration, normalization, and summaries of high density oligonucleotide array probe level data. , 2003, Biostatistics.