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

D. Garcia-Domingo, E. Leonardo, A. Grandien, P. Martinez, J. Pablo Albar, Juan Carlos Izpisua Belmonte, C. Martinez-A*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

The DIO-1 (death inducer-obliterator-1) gene, identified by differential display PCR in pre-B WOL-1 cells undergoing apoptosis, encodes a putative transcription factor whose protein has two Zn finger motifs, nuclear localization signals, and transcriptional activation domains, expressed in the limb interdigitating webs during development. When overexpressed, DIO-1 translocates to the nucleus and activates apoptosis in vitro. Nuclear translocation as well as induction of apoptosis are lost after deletion of the nuclear localization sequences. DIO-1 apoptotic induction is prevented by caspase inhibitors and Bcl-2 overexpression. The in vivo role of DIO-1 was studied by misexpressing DIO-1 during chicken limb development. The most frequently observed phenotype was an arrest in limb outgrowth, an effect that correlates with the inhibition of mesodermal and ectodermal genes involved in this process. Our data demonstrate the ability of DIO-1 to trigger apoptotic processes in vitro and suggest a role for this gene in cell death during development.

Original languageEnglish (US)
Pages (from-to)7992-7997
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number14
DOIs
StatePublished - Jul 6 1999

Keywords

  • Interdigital webs
  • Transcription factors

ASJC Scopus subject areas

  • General

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