A Role for AIF in Embryogenesis

Apoptosis-inducing factor (AIF) appears to be involved in a second pathway of programmed cell death that does not rely on the cytochrome c-Apaf1-caspase 9 pathway. Joza et al. knocked out the aif gene in embryonic stem (ES) cells ( aif /y ) and found that these cells did not contribute to chimeric mice when injected into blastocysts, but did retain their ability to differentiate into endoderm, mesoderm, and ectoderm as ES cells in culture. When the ES cells formed embryoid bodies, the aif /y ES cells failed to undergo cell death and normal cavitation (an essential step in the initiation of gastrulation), suggesting that AIF may control a very early apoptotic event in embryogenesis. Analysis of the characteristics of the programmed cell death exhibited during cavitation suggest that the pathway requires AIF, is genetically separable from the Apaf1-caspase 9 pathway, and can occur without activation of caspase 3. N. Joza, S. A. Susin, E. Daugas, W. L. Stanford, S. K. Cho, C. Y. J. Li, T. Sasaki, A. J. Elia, H.-Y. M. Cheng, L. Ravagnan, K. F. Ferri, N. Zamzami, A. Wakeham, R. Hakem, H. Yoshida, Y.-Y. Kong, T. W. Mak, J. C. Zúñiga-Pflücker, G. Kroemer, J. M. Penninger, Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death. Nature 410 , 549-554 (2001). [Online Journal]