Deletion of sf3b4 causes splicing defects and gene dysregulation that disrupt craniofacial development and survival.
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| Main Authors: | , , , , , |
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| Format: | Artículo científico |
| Language: | en |
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Disease models & mechanisms
2025
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| _version_ | 1868266226148442112 |
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| author | Griffin, Casey Coppenrath, Kelsey Khan, Doha Lin, Ziyan Horb, Marko Saint-Jeannet, Jean-Pierre |
| author_facet | Griffin, Casey Coppenrath, Kelsey Khan, Doha Lin, Ziyan Horb, Marko Saint-Jeannet, Jean-Pierre Griffin, Casey Coppenrath, Kelsey Khan, Doha Lin, Ziyan Horb, Marko Saint-Jeannet, Jean-Pierre |
| collection | PubMed - marine biology |
| contents | Deletion of sf3b4 causes splicing defects and gene dysregulation that disrupt craniofacial development and survival. Griffin, Casey Coppenrath, Kelsey Khan, Doha Lin, Ziyan Horb, Marko Saint-Jeannet, Jean-Pierre Animals RNA Splicing Factors Neural Crest RNA Splicing Gene Expression Regulation, Developmental Xenopus Gene Deletion Xenopus Proteins Skull Exons Cell Survival Cell Movement Embryo, Nonmammalian CRISPR-Cas Systems Cartilage Mandibulofacial Dysostosis Craniofacial Abnormalities Nager and Rodriguez syndromes are rare craniofacial and limb disorders characterized by midface retrusion, micrognathia, absent thumbs and radial hypoplasia. These disorders result from haploinsufficiency of SF3B4 (splicing factor 3b, subunit 4), a component of the pre-mRNA spliceosomal machinery. Although the spliceosome is present and functions in all cells of the body, most spliceosomopathies - including Nager and Rodriguez syndromes - are cell- or tissue-specific in their pathology. To understand the pathomechanism underlying these conditions, we generated a Xenopus tropicalis sf3b4 mutant line using CRISPR/Cas9 gene-editing technology. Homozygous deletion of sf3b4 is detrimental to the development of cranial neural crest (NC)-derived cartilage progenitors. Temporal RNA-sequencing analyses of mutant embryos identified an increase in exon-skipping events, followed by important transcriptional changes associated with an enrichment for terms consistent with defects in NC cell migration and survival. We propose that disruption of these processes may underly the pathogenesis of Nager and Rodriguez syndromes. |
| format | Artículo científico |
| id | pubmed_40126363 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Disease models & mechanisms |
| record_format | pubmed |
| spellingShingle | Deletion of sf3b4 causes splicing defects and gene dysregulation that disrupt craniofacial development and survival. Griffin, Casey Coppenrath, Kelsey Khan, Doha Lin, Ziyan Horb, Marko Saint-Jeannet, Jean-Pierre Animals RNA Splicing Factors Neural Crest RNA Splicing Gene Expression Regulation, Developmental Xenopus Gene Deletion Xenopus Proteins Skull Exons Cell Survival Cell Movement Embryo, Nonmammalian CRISPR-Cas Systems Cartilage Mandibulofacial Dysostosis Craniofacial Abnormalities Deletion of sf3b4 causes splicing defects and gene dysregulation that disrupt craniofacial development and survival. Griffin, Casey Coppenrath, Kelsey Khan, Doha Lin, Ziyan Horb, Marko Saint-Jeannet, Jean-Pierre Animals RNA Splicing Factors Neural Crest RNA Splicing Gene Expression Regulation, Developmental Xenopus Gene Deletion Xenopus Proteins Skull Exons Cell Survival Cell Movement Embryo, Nonmammalian CRISPR-Cas Systems Cartilage Mandibulofacial Dysostosis Craniofacial Abnormalities Nager and Rodriguez syndromes are rare craniofacial and limb disorders characterized by midface retrusion, micrognathia, absent thumbs and radial hypoplasia. These disorders result from haploinsufficiency of SF3B4 (splicing factor 3b, subunit 4), a component of the pre-mRNA spliceosomal machinery. Although the spliceosome is present and functions in all cells of the body, most spliceosomopathies - including Nager and Rodriguez syndromes - are cell- or tissue-specific in their pathology. To understand the pathomechanism underlying these conditions, we generated a Xenopus tropicalis sf3b4 mutant line using CRISPR/Cas9 gene-editing technology. Homozygous deletion of sf3b4 is detrimental to the development of cranial neural crest (NC)-derived cartilage progenitors. Temporal RNA-sequencing analyses of mutant embryos identified an increase in exon-skipping events, followed by important transcriptional changes associated with an enrichment for terms consistent with defects in NC cell migration and survival. We propose that disruption of these processes may underly the pathogenesis of Nager and Rodriguez syndromes. |
| title | Deletion of sf3b4 causes splicing defects and gene dysregulation that disrupt craniofacial development and survival. |
| topic | Animals RNA Splicing Factors Neural Crest RNA Splicing Gene Expression Regulation, Developmental Xenopus Gene Deletion Xenopus Proteins Skull Exons Cell Survival Cell Movement Embryo, Nonmammalian CRISPR-Cas Systems Cartilage Mandibulofacial Dysostosis Craniofacial Abnormalities |
| url | https://pubmed.ncbi.nlm.nih.gov/40126363/ |