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Regulation of the Pax6 : Pax6(5a) mRNA ratio in the developing mammalian brain

By Jeni Pinson, John O Mason, T Ian Simpson and David J Price

Abstract

BACKGROUND: Early in mammalian brain development cell proliferation generates a population of progenitor cells whose subsequent divisions produce increasing numbers of postmitotic neurons. Pax6 affects both processes and it has been suggested that this changing role is due at least in part to changes in the relative concentrations of its two main isoforms, (i) Pax6 and (ii) Pax6(5a), created by insertion of a 42 bp exon (exon 5a) into one of the two DNA-binding domains. Crucially, however, no previous study has determined whether the ratio between Pax6 and Pax6(5a) transcripts alters during mammalian neurogenesis in vivo. RESULTS: Using RNase protection assays, we show that Pax6 transcripts are 6–10 times more prevalent than Pax6(5a) transcripts early in neurogenesis in the murine telencephalon, diencephalon and hindbrain and that the ratio later falls significantly to about 3:1 in these regions. CONCLUSION: These changes in vivo are similar in magnitude to those shown previously to alter target gene activity in vitro and might, therefore, allow the single mammalian Pax6 gene to carry out different functions at different times in mammalian brain development

Topics: Research Article
Publisher: BioMed Central
Year: 2005
DOI identifier: 10.1186/1471-213X-5-13
OAI identifier: oai:pubmedcentral.nih.gov:1182360
Provided by: PubMed Central

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Citations

  1. (2002). Cvekl A: A comparative cDNA microarray analysis reveals a spectrum of genes regulated by Pax6 in mouse lens. Genes Cells
  2. (2004). Cvekl A: Functional interactions between alternatively spliced forms of Pax6 in crystallin gene regulation and in haploinsufficiency. Nucleic Acids Res
  3. (2002). Cvekl A: Identification of genes downstream of Pax6 in the mouse lens using cDNA microarrays.
  4. (2002). Glial cells generate neurons: the role of the transcription factor Pax6. Nat Neurosci
  5. (2004). Gotz M: Molecular dissection of Pax6 function: the specific roles of the paired domain and homeodomain in brain development. Development
  6. (2004). Growth and specification of the eye are controlled independently by Eyegone and Eyeless in Drosophila melanogaster. Nat Genet
  7. (2004). Growth and specification: fly Pax6 homologs eyegone and eyeless have distinct functions. Bioessays
  8. (1991). Gruss P: Pax-6, a murine paired box gene, is expressed in the developing CNS. Development
  9. (1994). Identification of a Pax paired domain recognition sequence and evidence for DNAdependent conformational changes.
  10. (1991). Mouse small eye results from mutations in a paired-like homeobox-containing gene. Nature
  11. (2002). Pax6 is required to regulate the cell cycle and the rate of progression from symmetrical to asymmetrical division in mammalian cortical progenitors. Development
  12. (1991). Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region. Cell
  13. (1994). RL: Two independent and interactive DNA-binding subdomains of the Pax6 paired domain are regulated by alternative splicing. Genes Dev
  14. (1998). Tyrosine phosphorylation of platelet derived growth factor beta receptors in coronary artery lesions: implications for vascular remodelling after directional coronary atherectomy and unstable angina pectoris. Heart

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