The Mdm2 gene of zebrafish (Danio rerio): preferential expression duping development of neural and muscular tissues, and absence of tumor formation after overexpression of its cDNA during early embryogenesis

The Mdm2 protein is most probably the main negative cellular regulator of t he p53 turner-suppressor protein. It was found to be overexpressed in a gre at number of human tumors and is considered as a potential target for anti- tumor therapies. Mdm2 is an essential gene in mice, yet its role in normal development and tissue differentiation is unknown. In order to study the ro le of this important protein in an evolutionary perspective, we cloned atl Mdm2 cDNA from the fish Danio rerio and analyzed its expression pattern as well as the phenotypic consequences of its overexpression. The main functio nal domains as well as the interaction between Mdm2 and p53 are conserved i n zebrafish. Moreover, we show here that the gene is expressed specifically during early development in neural and muscular tissues. Surprisingly, mic roinjection of Mdm2 mRNA in two-cell-stage embryos led to inhibition of cel lular convergence during gastrulation. The clones derived from Mdma microin jected blastomeres were significantly smaller than those derived from contr ol microinjections, and, in contrast to what was observed in Xenopus, did n ot develop tumors. Our results suggest that Mdm2 expression may be importan t during the differentiation of neural and muscular tissues of zebrafish. T hey also point to important differences between phyla in the susceptibility to tumor formation.