Pak1ip1 Loss-of-Function Leads to Cell Cycle Arrest, Loss of Neural Crest Cells, and Craniofacial Abnormalities
Neural crest cells (NCCs) comprise a transient progenitor cell population of neuroepithelial origin that contributes to a variety of cell types throughout vertebrate embryos including most mesenchymal cells of the cranial and facial structures. Consequently, abnormal NCC development underlies a vari...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.510063/full |
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| author | Alexios A. Panoutsopoulos Alexios A. Panoutsopoulos Angelo Harlan De Crescenzo Angelo Harlan De Crescenzo Albert Lee Albert Lee Amelia MacKenzie Lu Adam P. Ross Adam P. Ross Laura N. Borodinsky Laura N. Borodinsky Ralph Marcucio Paul A. Trainor Paul A. Trainor Konstantinos S. Zarbalis Konstantinos S. Zarbalis Konstantinos S. Zarbalis |
| author_facet | Alexios A. Panoutsopoulos Alexios A. Panoutsopoulos Angelo Harlan De Crescenzo Angelo Harlan De Crescenzo Albert Lee Albert Lee Amelia MacKenzie Lu Adam P. Ross Adam P. Ross Laura N. Borodinsky Laura N. Borodinsky Ralph Marcucio Paul A. Trainor Paul A. Trainor Konstantinos S. Zarbalis Konstantinos S. Zarbalis Konstantinos S. Zarbalis |
| author_sort | Alexios A. Panoutsopoulos |
| collection | DOAJ |
| description | Neural crest cells (NCCs) comprise a transient progenitor cell population of neuroepithelial origin that contributes to a variety of cell types throughout vertebrate embryos including most mesenchymal cells of the cranial and facial structures. Consequently, abnormal NCC development underlies a variety of craniofacial defects including orofacial clefts, which constitute some of the most common birth defects. We previously reported the generation of manta ray (mray) mice that carry a loss-of-function allele of the gene encoding the preribosomal factor Pak1ip1. Here we describe cranioskeletal abnormalities in homozygous mray mutants that arise from a loss of NCCs after their specification. Our results show that the localized loss of cranial NCCs in the developing frontonasal prominences is caused by cell cycle arrest and cell death. In addition, and consistent with deficits in ribosome biosynthesis, homozygous mray mutants display decreased protein biosynthesis, further linking Pak1ip1 to a role in ribosome biogenesis. |
| first_indexed | 2024-12-17T03:32:36Z |
| format | Article |
| id | doaj.art-ee23303e1c1a4a44a8dec0dc3164c2e5 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-17T03:32:36Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-ee23303e1c1a4a44a8dec0dc3164c2e52022-12-21T22:05:13ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-09-01810.3389/fcell.2020.510063510063Pak1ip1 Loss-of-Function Leads to Cell Cycle Arrest, Loss of Neural Crest Cells, and Craniofacial AbnormalitiesAlexios A. Panoutsopoulos0Alexios A. Panoutsopoulos1Angelo Harlan De Crescenzo2Angelo Harlan De Crescenzo3Albert Lee4Albert Lee5Amelia MacKenzie Lu6Adam P. Ross7Adam P. Ross8Laura N. Borodinsky9Laura N. Borodinsky10Ralph Marcucio11Paul A. Trainor12Paul A. Trainor13Konstantinos S. Zarbalis14Konstantinos S. Zarbalis15Konstantinos S. Zarbalis16Department of Pathology and Laboratory Medicine, School of Medicine, University of California, Davis, Davis, CA, United StatesInstitute for Pediatric Regenerative Medicine, Shriners Hospitals for Children – Northern California, Sacramento, CA, United StatesDepartment of Pathology and Laboratory Medicine, School of Medicine, University of California, Davis, Davis, CA, United StatesInstitute for Pediatric Regenerative Medicine, Shriners Hospitals for Children – Northern California, Sacramento, CA, United StatesDepartment of Pathology and Laboratory Medicine, School of Medicine, University of California, Davis, Davis, CA, United StatesInstitute for Pediatric Regenerative Medicine, Shriners Hospitals for Children – Northern California, Sacramento, CA, United StatesDavid B. Falk College of Sport and Human Dynamics – Department of Public Health, Syracuse University, Syracuse, NY, United StatesDepartment of Pathology and Laboratory Medicine, School of Medicine, University of California, Davis, Davis, CA, United StatesInstitute for Pediatric Regenerative Medicine, Shriners Hospitals for Children – Northern California, Sacramento, CA, United StatesInstitute for Pediatric Regenerative Medicine, Shriners Hospitals for Children – Northern California, Sacramento, CA, United StatesDepartment of Physiology and Membrane Biology, School of Medicine, University of California, Davis, Davis, CA, United StatesDepartment of Orthopedic Surgery, School of Medicine, University of California, San Francisco, San Francisco, CA, United StatesStowers Institute for Medical Research, Kansas City, MO, United StatesDepartment of Anatomy and Cell Biology, School of Medicine, The University of Kansas Medical Center, Kansas, KS, United StatesDepartment of Pathology and Laboratory Medicine, School of Medicine, University of California, Davis, Davis, CA, United StatesInstitute for Pediatric Regenerative Medicine, Shriners Hospitals for Children – Northern California, Sacramento, CA, United StatesMIND Institute, University of California, Davis, Davis, CA, United StatesNeural crest cells (NCCs) comprise a transient progenitor cell population of neuroepithelial origin that contributes to a variety of cell types throughout vertebrate embryos including most mesenchymal cells of the cranial and facial structures. Consequently, abnormal NCC development underlies a variety of craniofacial defects including orofacial clefts, which constitute some of the most common birth defects. We previously reported the generation of manta ray (mray) mice that carry a loss-of-function allele of the gene encoding the preribosomal factor Pak1ip1. Here we describe cranioskeletal abnormalities in homozygous mray mutants that arise from a loss of NCCs after their specification. Our results show that the localized loss of cranial NCCs in the developing frontonasal prominences is caused by cell cycle arrest and cell death. In addition, and consistent with deficits in ribosome biosynthesis, homozygous mray mutants display decreased protein biosynthesis, further linking Pak1ip1 to a role in ribosome biogenesis.https://www.frontiersin.org/article/10.3389/fcell.2020.510063/fullneural crestdevelopmentorofacial cleftsmousePak1ip1ribosomopathies |
| spellingShingle | Alexios A. Panoutsopoulos Alexios A. Panoutsopoulos Angelo Harlan De Crescenzo Angelo Harlan De Crescenzo Albert Lee Albert Lee Amelia MacKenzie Lu Adam P. Ross Adam P. Ross Laura N. Borodinsky Laura N. Borodinsky Ralph Marcucio Paul A. Trainor Paul A. Trainor Konstantinos S. Zarbalis Konstantinos S. Zarbalis Konstantinos S. Zarbalis Pak1ip1 Loss-of-Function Leads to Cell Cycle Arrest, Loss of Neural Crest Cells, and Craniofacial Abnormalities Frontiers in Cell and Developmental Biology neural crest development orofacial clefts mouse Pak1ip1 ribosomopathies |
| title | Pak1ip1 Loss-of-Function Leads to Cell Cycle Arrest, Loss of Neural Crest Cells, and Craniofacial Abnormalities |
| title_full | Pak1ip1 Loss-of-Function Leads to Cell Cycle Arrest, Loss of Neural Crest Cells, and Craniofacial Abnormalities |
| title_fullStr | Pak1ip1 Loss-of-Function Leads to Cell Cycle Arrest, Loss of Neural Crest Cells, and Craniofacial Abnormalities |
| title_full_unstemmed | Pak1ip1 Loss-of-Function Leads to Cell Cycle Arrest, Loss of Neural Crest Cells, and Craniofacial Abnormalities |
| title_short | Pak1ip1 Loss-of-Function Leads to Cell Cycle Arrest, Loss of Neural Crest Cells, and Craniofacial Abnormalities |
| title_sort | pak1ip1 loss of function leads to cell cycle arrest loss of neural crest cells and craniofacial abnormalities |
| topic | neural crest development orofacial clefts mouse Pak1ip1 ribosomopathies |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.510063/full |
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