Subtle changes in the levels of BCL-2 proteins cause severe craniofacial abnormalities
- Author(s)
- Grabow, S; Kueh, AJ; Ke, F; Vanyai, HK; Sheikh, BN; Dengler, MA; Chiang, W; Eccles, S; Smyth, IM; Jones, LK; de Sauvage, FJ; Scott, M; Whitehead, L; Voss, AK; Strasser, A;
- Details
- Publication Year 2018-09-18,Volume 24,Issue #12,Page 3285-3295.e4
- Journal Title
- Cell Reports
- Publication Type
- Journal Article
- Abstract
- Apoptotic cell death removes unwanted cells and is regulated by interactions between pro-survival and pro-apoptotic members of the BCL-2 protein family. The regulation of apoptosis is thought to be crucial for normal embryonic development. Accordingly, complete loss of pro-survival MCL-1 or BCL-XL (BCL2L1) causes embryonic lethality. However, it is not known whether minor reductions in pro-survival proteins could cause developmental abnormalities. We explored the rate-limiting roles of MCL-1 and BCL-XL in development and show that combined loss of single alleles of Mcl-1 and Bcl-x causes neonatal lethality. Mcl-1(+/-);Bcl-x(+/-) mice display craniofacial anomalies, but additional loss of a single allele of pro-apoptotic Bim (Bcl2l11) restores normal development. These findings demonstrate that the control of cell survival during embryogenesis is finely balanced and suggest that some human craniofacial defects, for which causes are currently unknown, may be due to subtle imbalances between pro-survival and pro-apoptotic BCL-2 family members.
- Publisher
- Cell Press
- Research Division(s)
- Molecular Genetics Of Cancer; Development And Cancer; Systems Biology And Personalised Medicine
- PubMed ID
- 30232009
- Publisher's Version
- https://doi.org/10.1016/j.celrep.2018.08.048
- Open Access at Publisher's Site
https://doi.org/10.1016/j.celrep.2018.08.048- NHMRC Grants
- NHMRC/1016701, NHMRC/1020363, NHMRC/575512, NHMRC/1081421, NHMRC/1051078,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2018-10-11 04:23:15
Last Modified: 2018-10-12 03:14:14