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| Status |
Public on Feb 26, 2024 |
| Title |
Sf3b4 mutation in Xenopus tropicalis causes RNA splicing defects and gene dysregulation across development and disrupts cranial neural crest cell migration and survival |
| Organism |
Xenopus tropicalis |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Nager syndrome is a rare craniofacial and limb disorder characterized by midface retrusion, micrognathia, absent thumbs, and radial hypoplasia. This disorder results from haploinsufficiency of SF3B4 (splicing factor 3b, subunit 4) a component of the pre-mRNA spliceosomal machinery. The spliceosome is a complex of RNA and proteins that function together to remove introns and join exons from transcribed pre-mRNA. While the spliceosome is present and functions in all cells of the body, most spliceosomopathies – including Nager syndrome – are cell/tissue-specific in their pathology. In Nager syndrome patients, it is the neural crest (NC)-derived craniofacial skeletal structures that are primarily affected. To understand the pathomechanism underlying this condition, we generated a Xenopus tropicalis sf3b4 mutant line using the CRISPR/Cas9 gene editing technology. Here we describe the sf3b4 mutant phenotype at neurula, tail bud, and tadpole stages, and performed temporal RNA-sequencing analysis to characterize the splicing events and transcriptional changes underlying this phenotype. Our data show that while loss of one copy of sf3b4 is largely inconsequential in Xenopus tropicalis, homozygous deletion of sf3b4 causes major splicing defects and gene dysregulation, which disrupt cranial NC cell migration and survival, thereby pointing at an essential role of Sf3b4 in craniofacial development.
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| Overall design |
Bulk RNA seq analysis of wildtype, heterozygous, and homozygous null sf3b4 mutant Xenopus tropicali embryos from stages 15, 25, and 35.
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| Contributor(s) |
Griffin C, Coppenrath K, Khan D, Juraver-Geslin H, Lin Z, Horb M, Saint-Jeannet J |
| Citation(s) |
38352410 |
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| Submission date |
Nov 30, 2023 |
| Last update date |
Feb 27, 2024 |
| Contact name |
Ziyan Lin |
| E-mail(s) |
[email protected]
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| Organization name |
NYU Grossman School of Medicine
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| Department |
Applied Bioinformatics Laboratories
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| Street address |
227 E 30th St.
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10016 |
| Country |
USA |
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| Platforms (1) |
| GPL30018 |
Illumina NovaSeq 6000 (Xenopus tropicalis) |
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| Samples (17)
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| Relations |
| BioProject |
PRJNA1047118 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE249075_RAW.tar |
1.7 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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