Genome-wide microarray comparison reveals downstream genes of Pax6 in the developing mouse cerebellum

Authors

  • Thomas J. Ha,

    1. Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, Canada
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  • Douglas J. Swanson,

    1. Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, Canada
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  • Roumyana Kirova,

    1. Mammalian Genetics and Genomics Group, Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA
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  • Joanna Yeung,

    1. Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, Canada
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  • Kunho Choi,

    1. Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, Canada
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  • Yiai Tong,

    1. Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN, USA
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  • Elissa J. Chesler,

    1. Mammalian Genetics and Genomics Group, Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA
    2. The Jackson Laboratory, Bar Harbor, ME, USA
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  • Daniel Goldowitz

    1. Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, Canada
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Dan Goldowitz, PhD, as above.
E-mail: dang@cmmt.ubc.ca

Abstract

The Pax6 transcription factor is expressed in cerebellar granule cells and when mutated, as in the Sey/Sey mouse, produces granule cells with disturbed survival and migration and with defects in neurite extension. The impact of Pax6 on other genes in the context of cerebellar development has not been identified. In this study, we performed transcriptome comparisons between wildtype and Pax6-null whole cerebellar tissue at embryonic day (E) 13.5, 15.5 and 18.5 using Affymetrix arrays (U74Av2). Statistical analyses identified 136 differentially regulated transcripts (FDR 0.05, 1.2-fold change cutoff) over time in Pax6-null cerebellar tissue. In parallel we examined the Math1-null granuloprival cerebellum and identified 228 down-regulated transcripts (FDR 0.05, 1.2-fold change cutoff). The intersection of these two microarray datasets produced a total of 21 differentially regulated transcripts. For a subset of the identified transcripts, we used qRT-PCR to validate the microarray data and demonstrated the expression in the rhombic lip lineage and differential expression in Pax6-null cerebellum with in situ hybridisation analysis. The candidate genes identified in this way represent direct or indirect Pax6-downstream genes involved in cerebellar development.

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