The role of the paired box embryonic transcription factor, Pax-3

In order to determine the precise role of Pax-3, its functional characteristics wee investigated in both the sensory neurone derived cell line, ND7 and primary neural crest cells.Analysis of Pax-3 during cellular differentiation, a process required for the formation of a mature neuronal cell, indicated a down regulation in Pax-3 expression, without direct effect upon cell proliferation. Pax-3 was therefore thought to be important for the maintenance of the undifferentiated cell phenotype, with its down regulation being an important regulatory process in the morphological differentiation of neuronal cells. Further more, Pax-3 was dependent on the presence of serum factors for high levels of expression and nuclear localisation.Specific down regulation of Pax-3 in ND7 cell lines with antisense technology was found to induce antisense Pax-3 RNA and rapidly reduce endogenous Pax-3 protein expression. This resulted in rapid changes in cell morphology from the normally rounded cell to a flattened cell phenotype exhibiting extensive neurite outgrowth. These cells also expressed genes such as the growth associated protein of 43KDa, characteristic of the mature neuron. Further analyses showed that expression of the FGF receptor 1 was down regulated in antisense Pax-3 cell lines.Investigation into the phosphorylation status of Pax-3 in ND7 cells revealed that Pax-3 may exist as a phosphoprotein within ND7 cells.In summary, the expression of Pax-3 appears essential to maintain the undifferentiated phenotype of immature neuronal cells. In the absence of Pax-3, cells may acquire characteristics of the mature neuronal cell, exhibiting altered gene expression and morphology. Pax-3 may also be post translationally regulated by phosphorylation. Phosphorylation/dephosphorylation may be important for precise regulation and function.