Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1083997 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28229835_1.fastq.gz | Fastqsanger.gz | |||
| SRR28229835_2.fastq.gz | Fastqsanger.gz | |||
| SRR28229836_1.fastq.gz | Fastqsanger.gz | |||
| SRR28229836_2.fastq.gz | Fastqsanger.gz | |||
| SRR28229838_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:Pathogenic variants in SF3B4 are responsible for the acrofacial disorders Nager and Rodriguez Syndrome, also known as SF3B4-related Syndromes, associated with malformations in the head, face, limbs, vertebrae as well as the heart. To uncover the etiology of craniofacial malformations found in SF3B4-related syndromes, mutant mouse lines with homozygous deletion of Sf3b4 in neural crest cells (NCC) were generated. Like in human patients, these embryos had craniofacial and cardiac malformations with variable expressivity and penetrance. The severity and survival of Sf3b4 NCC mutants was modified by the level of Sf3b4 in neighbouring non NCC. RNA sequencing analysis of heads of embryos prior to morphological abnormalities showed significant changes in expression of genes forming the NCC regulatory network, as well an increase in exon skipping. We identified several key transcription factors and histone modifiers involved in craniofacial and cardiac development with increased exon skipping. Increased exon skipping was also associated with use of a more proximal branch point, as well as an enrichment in thymidine bases in the 50bp around the branch points. We propose that decrease in Sf3b4 causes changes in the expression and splicing of transcripts required for proper craniofacial and cardiac development, leading to abnormalities.
2024-11-20 | GSE260990 | GEO
Project description:Mutations in Sf3b4, a component of the spliceosome, have been linked to craniofacial dismorphology known as Nager syndrome. To understand the role Sf3b4 in this condition, we knockdown Sf3b4 in Xenopus laevis embryos, and found that in these embryos the formation of neural crest-derived craniofacial skeletal structures was compromised. We performed RNA-Seq to identify the repertoire of genes affected by Sf3b4 splicing activity.
2020-04-30 | GSE143395 | GEO
Project description: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.
2024-02-26 | GSE249075 | GEO
Project description:Prevailing dogma maintains that Fetal Alcohol Syndrome (FAS) craniofacial and neurological birth defects are the sole consequence of maternal alcohol use during pregnancy. Using a physiologically relevant mouse model, we contrasted the incidence of alcohol-related growth and craniofacial defects between offspring derived from maternal, paternal, and dual parental alcohol exposures. Geometric morphometric analyses reveal that maternal, paternal, and dual parental exposures each induce unique craniofacial malformations and program dose-dependent increases in microcephaly, particularly in male offspring. Notably, dual parental exposures do not exhibit additive or synergistic effects; instead, our transcriptomic analyses demonstrate that each treatment programs distinct sex-specific changes in gene expression within the developing brain. Our data are the first to demonstrate that male drinking is a plausible driver of alcohol- related birth defects and that epidemiological examination of male alcohol consumption may help explain the enormous variation in FAS clinical presentations and severity.
2024-06-30 | GSE218362 | GEO
Project description:Proper retinoic acid (RA) signaling is essential for normal craniofacial development. Both excessive RA and RA deficiency in early embryonic stage led to a variety of craniofacial malformations, e.g., cleft palate, which have been investigated extensively. Dysregulated Wnt and Shh signaling were shown to underlie the pathogenesis of RA-induced craniofacial defects. In our present study, we showed a spatiotemporal-specific effect of RA signaling in regulating early development of facial prominences. While inhibited the Wnt activities in E12.5/E13.5 mouse palatal shelves, early exposure of excessive RA induced Wnt signaling and Wnt-related gene expression in mouse embryonic Frontonasal/Maxillary processes. A conserved regulatory network of miR-484-Fzd5 was identified to play critical roles in RA regulated craniofacial development using RNA-seq.
2023-07-29 | GSE238063 | GEO
Project description:Proper retinoic acid (RA) signaling is essential for normal craniofacial development. Both excessive RA and RA deficiency in early embryonic stage led to a variety of craniofacial malformations, e.g., cleft palate, which have been investigated extensively. Dysregulated Wnt and Shh signaling were shown to underlie the pathogenesis of RA-induced craniofacial defects. In our present study, we showed a spatiotemporal-specific effect of RA signaling in regulating early development of facial prominences. While inhibited the Wnt activities in E12.5/E13.5 mouse palatal shelves, early exposure of excessive RA induced Wnt signaling and Wnt-related gene expression in mouse embryonic Frontonasal/Maxillary processes. A conserved regulatory network of miR-484-Fzd5 was identified to play critical roles in RA regulated craniofacial development using RNA-seq.
2023-07-29 | GSE238062 | GEO
Project description:The search for developmental mechanisms driving vertebrate organogenesis has paved the way toward a deeper understanding of birth defects. During embryogenesis, parts of the heart and craniofacial muscles arise from pharyngeal mesoderm (PM) progenitors. Here, we reveal a hierarchical regulatory network of a set of transcription factors expressed in the PM that initiates heart and craniofacial organogenesis. Genetic perturbation of this network in mice resulted in heart and craniofacial muscle defects, revealing robust cross-regulation between its members. We identified Lhx2 as a novel player during cardiac and pharyngeal muscle development. Lhx2 and Tcf21 genetically interact with Tbx1, the major determinant in the etiology of DiGeorge/velo-cardio-facial/22q11.2 deletion syndrome. Furthermore, knockout of these genes in the mouse recapitulates specific cardiac features of this syndrome. We suggest that PM-derived cardiogenesis and myogenesis are network properties rather than properties specific to individual PM members. These findings shed new light on the developmental underpinnings of congenital defects. Mouse embryos were selected at E9.5, 10.5 and 11.5. We used Myf5Cre;RosaYFP in order to label all the myogenic lineage. Trunk (T) and Head (H) tissues were isolated, dispersed into a single cell suspension and FACS sorted for YFP+ population. Further analysis is described in Harel et al, PNAS (2012).
2012-11-26 | E-GEOD-42389 | biostudies-arrayexpress
Project description:This single cell transcriptome sequencing experiment is part of the study \\"Preclinical animal model of Diamond-Blackfan anemia with single amino acid mutation of ribosomal protein Rps19\\". A mouse model with this mutation develops features characteristic of human Diamond-Blackfan anemia, a rare bone marrow failure syndrome, including hematologic dysfunctions, early onset growth delay, intrinsic anemia, severe craniofacial, skeletal, urogenital, cardiovascular, and cerebral abnormalities leading to premature lethality during the adolescence of the mouse. This DBA mouse model exhibits cell intrinsic activation of the Trp53 signaling pathway in hematopoietic stem cells (HSCs) leading to reduced erythroid lineage development that may be rescued after inactivation of the tumor suppressor Trp53. The study uncovers that the development of the DBA phenotype significantly involves non-canonical components of the p53 signaling pathway in the etiopathogenesis of DBA with the Rps19R67∆ mutation leading to the disrupted hematopoietic hierarchy starting at the stage of short-term repopulating stem cells and the central role of induced Trp53 expression and upregulation of its non-canonical targets in the mediation of neural crest lineage deficiency-mediated development of craniofacial malformations in this model.
2023-05-01 | E-MTAB-12446 | biostudies-arrayexpress
Project description:The search for developmental mechanisms driving vertebrate organogenesis has paved the way toward a deeper understanding of birth defects. During embryogenesis, parts of the heart and craniofacial muscles arise from pharyngeal mesoderm (PM) progenitors. Here, we reveal a hierarchical regulatory network of a set of transcription factors expressed in the PM that initiates heart and craniofacial organogenesis. Genetic perturbation of this network in mice resulted in heart and craniofacial muscle defects, revealing robust cross-regulation between its members. We identified Lhx2 as a novel player during cardiac and pharyngeal muscle development. Lhx2 and Tcf21 genetically interact with Tbx1, the major determinant in the etiology of DiGeorge/velo-cardio-facial/22q11.2 deletion syndrome. Furthermore, knockout of these genes in the mouse recapitulates specific cardiac features of this syndrome. We suggest that PM-derived cardiogenesis and myogenesis are network properties rather than properties specific to individual PM members. These findings shed new light on the developmental underpinnings of congenital defects.
2012-11-26 | GSE42389 | GEO
Project description:Craniofacial morphogenesis is an intricate process that requires precise regulation of cell proliferation, migration, and differentiation. Perturbations of this process cause a series of craniofacial deformities. Dlx2 is a critical transcription factor that regulates the development of the first branchial arch. However, the transcriptional regulatory functions of Dlx2 during craniofacial development have been poorly understood due to the lack of animal models in that the levels of Dlx2 can be precisely modulated. In this study, we constructed a Rosa26 site-directed Dlx2 gene knock-in mouse model Rosa26CAG-LSL-Dlx2-3xFlag for conditionally overexpressing Dlx2. By breeding with Wnt1cre mice, we obtained Wnt1cre; Rosa26Dlx2/- mice in which Dlx2 is overexpressed in neural crest lineage at about three times the endogenous level. The Wnt1cre; Rosa26Dlx2/- mice exhibited consistent phenotypes that include cleft palate across generations and individual animals. Using this model, we demonstrated that Dlx2 caused cleft palate by affecting maxillary growth in the early-stage development of maxillary prominences. By performing bulk RNA-seq, we demonstrated that the overexpression of Dlx2 induced significant changes of many genes related to critical developmental pathways. In summary, our novel mouse model provides a reliable and consistent system for investigating the functions of Dlx2 during development and for dissecting the gene regulatory networks underlying craniofacial development.
2022-04-14 | GSE185279 | GEO