DIO-1 is a gene involved in onset of apoptosis in vitro, whose misexpression disrupts limb development

The DIO-1 (death inducer-obliterator-1) gene, identified by differential di splay PCR in pre-B WOL-1 cells undergoing apoptosis, encodes a putative tra nscription factor whose protein has two Zn finger motifs, nuclear localizat ion signals, and transcriptional activation domains, expressed in the limb interdigitating webs during development. When overexpressed, DIO-1 transloc ates to the nucleus and activates apoptosis in vitro. Nuclear translocation as well as induction of apoptosis are lost after deletion of the nuclear l ocalization sequences. DIO-1 apoptotic induction is prevented by caspase in hibitors and Bcl-2 overexpression. The in vivo role of DIO-1 was studied by misexpressing DIO-1 during chicken limb development. The most frequently o bserved phenotype was an arrest in limb outgrowth, an effect that correlate s with the inhibition of mesodermal and ectodermal genes involved in this p rocess. Our data demonstrate the ability of DIO-1 to trigger apoptotic proc esses in vitro and suggest a role for this gene in cell death during develo pment.