Subtle Changes in the Levels of BCL-2 Proteins Cause Severe Craniofacial Abnormalities
Summary: 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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718313342 |
| _version_ | 1819010304143523840 |
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| author | Stephanie Grabow Andrew J. Kueh Francine Ke Hannah K. Vanyai Bilal N. Sheikh Michael A. Dengler William Chiang Samantha Eccles Ian M. Smyth Lynelle K. Jones Frederic J. de Sauvage Mark Scott Lachlan Whitehead Anne K. Voss Andreas Strasser |
| author_facet | Stephanie Grabow Andrew J. Kueh Francine Ke Hannah K. Vanyai Bilal N. Sheikh Michael A. Dengler William Chiang Samantha Eccles Ian M. Smyth Lynelle K. Jones Frederic J. de Sauvage Mark Scott Lachlan Whitehead Anne K. Voss Andreas Strasser |
| author_sort | Stephanie Grabow |
| collection | DOAJ |
| description | Summary: 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. : Grabow et al. find that combined loss of single alleles of pro-survival Mcl-1 and Bcl-x causes craniofacial defects, including holoprosencephaly, a severe birth defect. Normal development is restored by concomitant loss of a single allele of pro-apoptotic Bim, revealing that cell survival and cell death during embryogenesis are finely balanced. Keywords: MCL-1, MCL1, BCL-XL, BCL2L1, BIM, BCL2L11, apoptosis, embryonic development, holoprosencephaly, cyclopia |
| first_indexed | 2024-12-21T01:10:08Z |
| format | Article |
| id | doaj.art-b958c8def9dc4e4eb7387f18421e59a4 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T01:10:08Z |
| publishDate | 2018-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-b958c8def9dc4e4eb7387f18421e59a42022-12-21T19:20:57ZengElsevierCell Reports2211-12472018-09-01241232853295.e4Subtle Changes in the Levels of BCL-2 Proteins Cause Severe Craniofacial AbnormalitiesStephanie Grabow0Andrew J. Kueh1Francine Ke2Hannah K. Vanyai3Bilal N. Sheikh4Michael A. Dengler5William Chiang6Samantha Eccles7Ian M. Smyth8Lynelle K. Jones9Frederic J. de Sauvage10Mark Scott11Lachlan Whitehead12Anne K. Voss13Andreas Strasser14The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC 3052, Australia; Corresponding authorThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, AustraliaDevelopment and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia; Department of Anatomy and Developmental Biology and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC 3800, AustraliaDevelopment and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia; Department of Anatomy and Developmental Biology and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC 3800, AustraliaDepartment of Molecular Oncology, Genentech, South San Francisco, CA 94080, USAThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC 3052, Australia; Corresponding authorThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC 3052, Australia; Corresponding authorSummary: 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. : Grabow et al. find that combined loss of single alleles of pro-survival Mcl-1 and Bcl-x causes craniofacial defects, including holoprosencephaly, a severe birth defect. Normal development is restored by concomitant loss of a single allele of pro-apoptotic Bim, revealing that cell survival and cell death during embryogenesis are finely balanced. Keywords: MCL-1, MCL1, BCL-XL, BCL2L1, BIM, BCL2L11, apoptosis, embryonic development, holoprosencephaly, cyclopiahttp://www.sciencedirect.com/science/article/pii/S2211124718313342 |
| spellingShingle | Stephanie Grabow Andrew J. Kueh Francine Ke Hannah K. Vanyai Bilal N. Sheikh Michael A. Dengler William Chiang Samantha Eccles Ian M. Smyth Lynelle K. Jones Frederic J. de Sauvage Mark Scott Lachlan Whitehead Anne K. Voss Andreas Strasser Subtle Changes in the Levels of BCL-2 Proteins Cause Severe Craniofacial Abnormalities Cell Reports |
| title | Subtle Changes in the Levels of BCL-2 Proteins Cause Severe Craniofacial Abnormalities |
| title_full | Subtle Changes in the Levels of BCL-2 Proteins Cause Severe Craniofacial Abnormalities |
| title_fullStr | Subtle Changes in the Levels of BCL-2 Proteins Cause Severe Craniofacial Abnormalities |
| title_full_unstemmed | Subtle Changes in the Levels of BCL-2 Proteins Cause Severe Craniofacial Abnormalities |
| title_short | Subtle Changes in the Levels of BCL-2 Proteins Cause Severe Craniofacial Abnormalities |
| title_sort | subtle changes in the levels of bcl 2 proteins cause severe craniofacial abnormalities |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718313342 |
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