@article{1a6174241f084648b220d8496ff3070a,
title = "Embryogenesis and Adult Life in the Absence of Intrinsic Apoptosis Effectors BAX, BAK, and BOK",
abstract = "Intrinsic apoptosis, reliant on BAX and BAK, has been postulated to be fundamental for morphogenesis, but its precise contribution to this process has not been fully explored in mammals. Our structural analysis of BOK suggests close resemblance to BAX and BAK structures. Notably, Bok−/−Bax−/−Bak−/− animals exhibited more severe defects and died earlier than Bax−/−Bak−/− mice, implying that BOK has overlapping roles with BAX and BAK during developmental cell death. By analyzing Bok−/−Bax−/−Bak−/− triple-knockout mice whose cells are incapable of undergoing intrinsic apoptosis, we identified tissues that formed well without this process. We provide evidence that necroptosis, pyroptosis, or autophagy does not substantially substitute for the loss of apoptosis. Albeit very rare, unexpected attainment of adult Bok−/−Bax−/−Bak−/− mice suggests that morphogenesis can proceed entirely without apoptosis mediated by these proteins and possibly without cell death in general. Although apoptosis has been observed in many organs and tissues during embryonic development, it is not strictly required for the development of most organs.",
keywords = "aortic arch defects, BCL-2 proteins, BOK, cleft palate, exencephaly, facial cleft, midline defects, ompalocele, programmed cell death, spina bifida",
author = "Ke, {Francine F.S.} and Vanyai, {Hannah K.} and Cowan, {Angus D.} and Delbridge, {Alex R.D.} and Lachlan Whitehead and Stephanie Grabow and Czabotar, {Peter E.} and Voss, {Anne K.} and Andreas Strasser",
note = "Funding Information: We thank Drs. T. Kaufmann, D.C.S. Huang, S.J. Korsmeyer, and C. Thompson for mice; C. D{\textquoteright}Alessando and G. Siciliano for expert animal care; WEHI Histology and Imaging services department; Z. Liu and R. Salvamoser for lysates for western blots; Drs. J. Vince and N. Lalaoui for antibodies; A. Wardak for western blot optimization; S. Monard for FACS assistance; and D. Anbarci for photography of histological slides for analysis. We also thank Professor P.M. Colman for discussions and comments regarding the BOK structure and the beamline staff at the Australian Synchrotron. Crystallization experiments were performed at the Bio21 C3 Collaborative Crystallisation Centre. This work was supported by grants and fellowships from the Cancer Council Victoria (F.F.S.K., S.G.), the Lady Tata Memorial Trust (S.G.) the Leukaemia Foundation Australia (F.F.S.K., S.G.), Australian Government Postgraduate Award (H.K.V.), the National Health and Medical Research Council (NHMRC Program Grant 1016701 to A.S.; NHMRC Project grant 1051078 to A.K.V.; NHMRC project grant 1079706 to P.E.C.; and NHMRC Fellowships 1020363 to A.S., 575512 and 1081421 to A.K.V., and 1079700 to P.E.C.), the Leukemia and Lymphoma Society (SCOR Grant 7001-03 ; to A.S.), and the operational infrastructure grants through the Australian Government IRIISS and the Victorian State Government OIS . Funding Information: We thank Drs. T. Kaufmann, D.C.S. Huang, S.J. Korsmeyer, and C. Thompson for mice; C. D'Alessando and G. Siciliano for expert animal care; WEHI Histology and Imaging services department; Z. Liu and R. Salvamoser for lysates for western blots; Drs. J. Vince and N. Lalaoui for antibodies; A. Wardak for western blot optimization; S. Monard for FACS assistance; and D. Anbarci for photography of histological slides for analysis. We also thank Professor P.M. Colman for discussions and comments regarding the BOK structure and the beamline staff at the Australian Synchrotron. Crystallization experiments were performed at the Bio21 C3 Collaborative Crystallisation Centre. This work was supported by grants and fellowships from the Cancer Council Victoria (F.F.S.K., S.G.), the Lady Tata Memorial Trust (S.G.) the Leukaemia Foundation Australia (F.F.S.K., S.G.), Australian Government Postgraduate Award (H.K.V.), the National Health and Medical Research Council (NHMRC Program Grant 1016701 to A.S.; NHMRC Project grant 1051078 to A.K.V.; NHMRC project grant 1079706 to P.E.C.; and NHMRC Fellowships 1020363 to A.S., 575512 and 1081421 to A.K.V., and 1079700 to P.E.C.), the Leukemia and Lymphoma Society (SCOR Grant 7001-03; to A.S.), and the operational infrastructure grants through the Australian Government IRIISS and the Victorian State Government OIS. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2018",
month = may,
day = "17",
doi = "10.1016/j.cell.2018.04.036",
language = "English",
volume = "173",
pages = "1217--1230.e17",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier",
number = "5",
}