Rôle des gènes pax4 et arx au cours de la différenciation endocrine pancréatique chez le poisson zèbre

Genetic studies in mouse have demonstrated the crucial function of PAX4 in pancreatic cell differentiation. This transcription factor specifies β- and δ-cell fate at the expense of α-cell identity by repressing Arx gene expression and ectopic expression of PAX4 in α-cells is sufficient to convert them into β-cells. Surprisingly, no Pax4 orthologous gene can be found in chicken and xenopus tropicalis raising the question of the function of Pax4 gene in lower vertebrates such as in fish. In the present study, we have analysed the expression and the function of the orthologous pax4 gene in zebrafish. In zebrafish, pax4 is not required for the generation of pancreatic β- and δ-cells, unlike its crucial role in the differentiation of these cell types in mouse. On the other hand, the mutual repression between Arx and Pax4 is observed in both mouse and zebrafish. These data suggests that the main original function of Pax4 during vertebrate evolution was to modulate the number of pancreatic α-cells and its role in β-cells differentiation appeared later in vertebrate evolution.