TY - JOUR
T1 - Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development
AU - Cecconi, Francesco
AU - Alvarez-Bolado, Gonzalo
AU - Meyer, Barbara I.
AU - Roth, Kevin A.
AU - Gruss, Peter
PY - 1998/9/18
Y1 - 1998/9/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0032544449&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032544449&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(00)81732-8
DO - 10.1016/S0092-8674(00)81732-8
M3 - Article
C2 - 9753320
AN - SCOPUS:0032544449
VL - 94
SP - 727
EP - 737
JO - Cell
JF - Cell
SN - 0092-8674
IS - 6
ER -