Subtle Changes in the Levels of BCL-2 Proteins Cause Severe Craniofacial Abnormalities

Cell Reports
S GrabowAndreas Strasser

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.

Citations

Nov 9, 2019·Genes & Development·Verena LabiKlaus Rajewsky
Mar 15, 2020·Cell Death & Disease·Francine KeAndreas Strasser
Mar 10, 2020·F1000Research·Anne K Voss, Andreas Strasser
Nov 5, 2019·F1000Research·Andrew Gilmore, Louise King
Nov 10, 2020·Cell Death and Differentiation·James M PembertonDavid W Andrews
Nov 14, 2020·Genes & Development·Ayan T RayPhilippe Soriano
Feb 19, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Sarah Kehr, Meike Vogler
Jul 14, 2020·Journal of Stomatology, Oral and Maxillofacial Surgery·M A SaghiriP Freag
Jun 9, 2021·Cell Death and Differentiation·Diane MoujalledJeffrey R Liddell

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