Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development

Francesco Cecconi, Gonzalo Alvarez-Bolado, Barbara I. Meyer, Kevin A. Roth, Peter Gruss

Research output: Contribution to journalArticlepeer-review

Abstract

The cytosolic protein APAF1, human homolog of C. elegans CED-4, participates in the CASPASE 9 (CASP9)-dependent activation of CASP3 in the general apoptotic pathway. We have generated by gene trap a null allele of the murine Apaf1. Homozygous mutants die at embryonic day 16.5. Their phenotype includes severe craniofacial malformations, brain overgrowth, persistence of the interdigital webs, and dramatic alterations of the lens and retina. Homozygous embryonic fibroblasts exhibit reduced response to various apoptotic stimuli. In situ immunodetection shows that the absence of Apaf1 protein prevents the activation of Casp3 in vivo. In agreement with the reported function of CED-4 in C. elegans, this phenotype can be correlated with a defect of apoptosis. Our findings suggest that Apaf1 is essential for Casp3 activation in embryonic brain and is a key regulator of developmental programmed cell death in mammals.

Original languageEnglish
Pages (from-to)727-737
Number of pages11
JournalCell
Volume94
Issue number6
DOIs
Publication statusPublished - Sep 18 1998

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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