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

Eur J Neurosci. 2012 Oct;36(7):2888-98. doi: 10.1111/j.1460-9568.2012.08221.x. Epub 2012 Jul 22.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cerebellum / embryology
  • Cerebellum / metabolism*
  • Comparative Genomic Hybridization
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / genetics*
  • Paired Box Transcription Factors / metabolism
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Transcriptome / genetics*

Substances

  • Atoh1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Eye Proteins
  • Homeodomain Proteins
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pax6 protein, mouse
  • RNA, Messenger
  • Repressor Proteins