The regulation of the embryonic transcription factor Pax-3

Abstract

Pax-3 belongs to a family of nine murine transcription factors, the Pax genes. These all contain a highly conserved DNA binding domain, the paired domain and play key roles in embryogenesis in the mouse. Pax-3 is expressed in neural crest cells, developing spinal cord and brain from embryonic day 8.5 post coitus. Expression is temporally and spatially regulated and is restricted to mitotic progenitor cells before the onset of differentiation. Pax-3 has previously been shown to be necessary fbr continued proliferation of the sensoiy neuron derived ND7 cell line. In this study the cell cycle transcription regulators E2F and the Myc/Max/Mad network have been shovm to control the expression of Pax-3 in ND7 cells. In addition their binding sites in the Pax-3 promoter have been identified and it has been shown that binding to these sites is cell-cycle dependent. This work has also looked at the subcellular localisation of Pax-3. Using fusions of Pax-3 and Enhanced Green Fluorescent Protein (EGFP) a Nuclear Localisation Sequence (NLS) has been identified in the Pax-3 protein. I have also shown that Pax- 3 nuclear import in primary neural crest cells is serum dependent. To date few target proteins of Pax-3 have been identified. Studies on an antisense Pax-3 cell line showed that suppression of Pax-3 expression led to the upregulation Snap-25 a protein involved in axonal outgrowth. I have shown that Pax-3 directly inhibits Snap-25 expression and located the Pax-3 binding site in the Snap-25 promoter.

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