Transcriptome and proteome analysis of early embryonic mouse brain development

Authors

  • Daniela Hartl,

    1. Institute for Human Genetics, Charité – University Medicine Berlin, Berlin, Germany
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    • These authors contributed equally to this work.

  • Martin Irmler,

    1. Institute for Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
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    • These authors contributed equally to this work.

  • Irmgard Römer,

    1. Institute for Human Genetics, Charité – University Medicine Berlin, Berlin, Germany
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  • Michael T. Mader,

    1. Institute of Stem Cell Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
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  • Lei Mao,

    1. Institute for Human Genetics, Charité – University Medicine Berlin, Berlin, Germany
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  • Claus Zabel,

    1. Institute for Human Genetics, Charité – University Medicine Berlin, Berlin, Germany
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  • Martin Hrabé de Angelis,

    1. Institute for Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
    2. Technical University Munich, Center of Life and Food Sciences Weihenstephan Chair of Experimental Genetics, Weihenstephan, Germany
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  • Johannes Beckers,

    1. Institute for Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
    2. Technical University Munich, Center of Life and Food Sciences Weihenstephan Chair of Experimental Genetics, Weihenstephan, Germany
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  • Joachim Klose Professor

    Corresponding author
    1. Institute for Human Genetics, Charité – University Medicine Berlin, Berlin, Germany
    • Institute for Human Genetics, Charité – University Medicine Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany Fax: +49-30-450-566904
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Abstract

Mouse embryonic brain development involves sequential differentiation of multipotent progenitors into neurons and glia cells. Using microarrays and large 2-DE, we investigated the mouse brain transcriptome and proteome of embryonic days 9.5, 11.5, and 13.5. During this developmental period, neural progenitor cells shift from proliferation to neuronal differentiation. As expected, we detected numerous expression changes between all time points investigated, but interestingly, the rate of alteration remained in a similar range within 2 days of development. Furthermore, up- and down-regulation of gene products was balanced at each time point which was also seen at embryonic days 16–18. We hypothesize that during embryonic development, the rate of gene expression alteration is rather constant due to limited cellular resources such as energy, space, and free water. A similar complexity in terms of expressed genes and proteins suggests that changes in relative concentrations rather than an increase in the number of gene products dominate cellular differentiation. In general, expression of metabolism and cell cycle related gene products was down-regulated when precursor cells switched from proliferation to neuronal differentiation (days 9.5–11.5), whereas neuron specific gene products were up-regulated. A detailed functional analysis revealed their implication in differentiation related processes such as rearrangement of the actin cytoskeleton as well as Notch- and Wnt-signaling pathways.

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