title: Loss of Aif function causes cell death in the mouse embryo, but the temporal progression of patterning is normal.
abstract: Apoptosis-inducing factor (AIF) is an evolutionarily conserved, ubiquitously expressed flavoprotein with NADH oxidase activity that is normally confined to mitochondria. In mammalian cells, AIF is released from mitochondria in response to apoptotic stimuli and translocates to the nucleus where it is thought to bind DNA and contribute to chromatinolysis and cell death in a caspase-independent manner. Here we describe the consequences of inactivating Aif in the early mouse embryo. Unexpectedly, we found that both the apoptosis-dependent process of cavitation in embryoid bodies and apoptosis associated with embryonic neural tube closure occur in the absence of AIF, indicating that Aif function is not required for apoptotic cell death in early mouse embryos. By embryonic day 9 (E9), loss of Aif function causes abnormal cell death, presumably because of reduced mitochondrial respiratory chain complex I activity. Because of this cell death, Aif null embryos fail to increase significantly in size after E9. Remarkably, patterning processes continue on an essentially normal schedule, such that E10 Aif null embryos with only approximately 1/10 the normal number of cells have the same somite number as their wild-type littermates. These observations show that pattern formation in the mouse can occur independent of embryo size and cell number.
authors.affiliation: Department of Anatomy, University of California-San Francisco, San Francisco, CA 94143, USA.
authors.forename: Doris
authors.initials: D
authors.lastname: Brown
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Yu
authors.forename: Nicholas
authors.initials: N
authors.lastname: Joza
authors.forename: Paule
authors.initials: P
authors.lastname: Bénit
authors.forename: Juanito
authors.initials: J
authors.lastname: Meneses
authors.forename: Meri
authors.initials: M
authors.lastname: Firpo
authors.forename: Pierre
authors.initials: P
authors.lastname: Rustin
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
authors.forename: Gail R
authors.initials: GR
authors.lastname: Martin
mesh_terms: D000818:Animals; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000502:physiology*; D019521:Body Patterning / Q000235:genetics; D002452:Cell Count; D042967:Electron Transport Complex I / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000201:enzymology / Q000648:ultrastructure; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D005804:Genes, Lethal; D051379:Mice; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000201:enzymology; D009154:Mutation
chemical_list: D051033:Apoptosis Inducing Factor; C494830:AIFM1 protein, mouse; D042967:Electron Transport Complex I