The Core Splicing Factors EFTUD2, SNRPB and TXNL4A Are Essential for Neural Crest and Craniofacial Development
Mandibulofacial dysostosis (MFD) is a human congenital disorder characterized by hypoplastic neural-crest-derived craniofacial bones often associated with outer and middle ear defects. There is growing evidence that mutations in components of the spliceosome are a major cause for MFD. Genetic varian...
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2022-07-01
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author | Byung-Yong Park Melanie Tachi-Duprat Chibuike Ihewulezi Arun Devotta Jean-Pierre Saint-Jeannet |
author_facet | Byung-Yong Park Melanie Tachi-Duprat Chibuike Ihewulezi Arun Devotta Jean-Pierre Saint-Jeannet |
author_sort | Byung-Yong Park |
collection | DOAJ |
description | Mandibulofacial dysostosis (MFD) is a human congenital disorder characterized by hypoplastic neural-crest-derived craniofacial bones often associated with outer and middle ear defects. There is growing evidence that mutations in components of the spliceosome are a major cause for MFD. Genetic variants affecting the function of several core splicing factors, namely <i>SF3B4</i>, <i>SF3B2</i>, <i>EFTUD2</i>, <i>SNRPB</i> and <i>TXNL4A</i>, are responsible for MFD in five related but distinct syndromes known as Nager and Rodriguez syndromes (NRS), craniofacial microsomia (CFM), mandibulofacial dysostosis with microcephaly (MFDM), cerebro-costo-mandibular syndrome (CCMS) and Burn–McKeown syndrome (BMKS), respectively. Animal models of NRS and MFDM indicate that MFD results from an early depletion of neural crest progenitors through a mechanism that involves apoptosis. Here we characterize the knockdown phenotype of Eftud2, Snrpb and Txnl4a in <i>Xenopus</i> embryos at different stages of neural crest and craniofacial development. Our results point to defects in cranial neural crest cell formation as the likely culprit for MFD associated with <i>EFTUD2</i>, <i>SNRPB</i> and <i>TXNL4A</i> haploinsufficiency, and suggest a commonality in the etiology of these craniofacial spliceosomopathies. |
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spelling | doaj.art-da89c03bb36147bcb3940f76d432a01b2023-11-23T17:02:36ZengMDPI AGJournal of Developmental Biology2221-37592022-07-011032910.3390/jdb10030029The Core Splicing Factors EFTUD2, SNRPB and TXNL4A Are Essential for Neural Crest and Craniofacial DevelopmentByung-Yong Park0Melanie Tachi-Duprat1Chibuike Ihewulezi2Arun Devotta3Jean-Pierre Saint-Jeannet4Department of Molecular Pathobiology, College of Dentistry, New York University, 345 East 24th Street, New York, NY 10010, USADepartment of Molecular Pathobiology, College of Dentistry, New York University, 345 East 24th Street, New York, NY 10010, USADepartment of Molecular Pathobiology, College of Dentistry, New York University, 345 East 24th Street, New York, NY 10010, USADepartment of Molecular Pathobiology, College of Dentistry, New York University, 345 East 24th Street, New York, NY 10010, USADepartment of Molecular Pathobiology, College of Dentistry, New York University, 345 East 24th Street, New York, NY 10010, USAMandibulofacial dysostosis (MFD) is a human congenital disorder characterized by hypoplastic neural-crest-derived craniofacial bones often associated with outer and middle ear defects. There is growing evidence that mutations in components of the spliceosome are a major cause for MFD. Genetic variants affecting the function of several core splicing factors, namely <i>SF3B4</i>, <i>SF3B2</i>, <i>EFTUD2</i>, <i>SNRPB</i> and <i>TXNL4A</i>, are responsible for MFD in five related but distinct syndromes known as Nager and Rodriguez syndromes (NRS), craniofacial microsomia (CFM), mandibulofacial dysostosis with microcephaly (MFDM), cerebro-costo-mandibular syndrome (CCMS) and Burn–McKeown syndrome (BMKS), respectively. Animal models of NRS and MFDM indicate that MFD results from an early depletion of neural crest progenitors through a mechanism that involves apoptosis. Here we characterize the knockdown phenotype of Eftud2, Snrpb and Txnl4a in <i>Xenopus</i> embryos at different stages of neural crest and craniofacial development. Our results point to defects in cranial neural crest cell formation as the likely culprit for MFD associated with <i>EFTUD2</i>, <i>SNRPB</i> and <i>TXNL4A</i> haploinsufficiency, and suggest a commonality in the etiology of these craniofacial spliceosomopathies.https://www.mdpi.com/2221-3759/10/3/29<i>Xenopus</i>neural crestcraniofacialmandibulofacial dysostosisapoptosisspliceosome |
spellingShingle | Byung-Yong Park Melanie Tachi-Duprat Chibuike Ihewulezi Arun Devotta Jean-Pierre Saint-Jeannet The Core Splicing Factors EFTUD2, SNRPB and TXNL4A Are Essential for Neural Crest and Craniofacial Development Journal of Developmental Biology <i>Xenopus</i> neural crest craniofacial mandibulofacial dysostosis apoptosis spliceosome |
title | The Core Splicing Factors EFTUD2, SNRPB and TXNL4A Are Essential for Neural Crest and Craniofacial Development |
title_full | The Core Splicing Factors EFTUD2, SNRPB and TXNL4A Are Essential for Neural Crest and Craniofacial Development |
title_fullStr | The Core Splicing Factors EFTUD2, SNRPB and TXNL4A Are Essential for Neural Crest and Craniofacial Development |
title_full_unstemmed | The Core Splicing Factors EFTUD2, SNRPB and TXNL4A Are Essential for Neural Crest and Craniofacial Development |
title_short | The Core Splicing Factors EFTUD2, SNRPB and TXNL4A Are Essential for Neural Crest and Craniofacial Development |
title_sort | core splicing factors eftud2 snrpb and txnl4a are essential for neural crest and craniofacial development |
topic | <i>Xenopus</i> neural crest craniofacial mandibulofacial dysostosis apoptosis spliceosome |
url | https://www.mdpi.com/2221-3759/10/3/29 |
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