Similar Datasets
Project description:Distribution of MOZ (KAT6A) in the genome and effects of MOZ on gene expression during mouse craniofacial development
| PRJNA555846 | ENA
Project description:The purpose of these data is to investigate the genetic perturbations which underlie the cleft palate phenotype in Kat6a and Dlx5 mutant mouse embryos. The palate develops from the maxillary portion of the first pharyngeal arches, commencing between E10.5 and E11.5 of mouse gestation.
2019-07-23 | GSE134608 | GEO
Project description:Carboxy-terminally tagged MOZ (Flag-V5-BIO tagged) was detected by ChIP-seq using anti-V5 antibody (Sigma, A7345) to precipitate chromatin associated with MOZ
2019-07-23 | GSE134607 | GEO
Project description:RNA-seq analysis of the effects of single and compound deletion of Moz (Kat6a) and/or Dlx5 during mouse craniofacial development
| PRJNA555853 | ENA
Project description:Alternative splicing acts as a fundamental mechanism to increase the number of functional transcripts that can be derived from the genome - and its appropriate regulation is required to direct normal development, differentiation, and physiology, in many species. Recent studies have highlighted that mutation of splicing factors, resulting in the disruption of alternative splicing, can have profound consequences for mammalian craniofacial development. However, there has been no systematic analysis of the dynamics of differential splicing during the critical period of face formation with respect to age, tissue layer, or prominence. Here we used deep RNA sequencing to profile transcripts expressed in the developing mouse face for both ectodermal and mesenchymal tissues from the three facial prominences at critical ages for facial development, embryonic days 10.5, 11.5, and 12.5. We also derived separate expression data from the nasal pit relating to the differentiation of the olfactory epithelium for a total of 60 independent datasets. Analysis of these datasets reveals the differential expression of multiple genes, but we find a similar number of genes are regulated only via differential splicing, indicating that alternative splicing is a major source of transcript diversity during facial development. Notably, splicing changes between tissue layers and over time are more prevalent than between prominences, with exon skipping the most common event. We next examined how the variation in splicing correlated with the expression of RNA binding proteins across the various datasets. Further, we assessed how binding sites for splicing regulatory molecules mapped with respect to intron exon boundaries. Overall these studies help define an alternative splicing regulatory program that has important consequences for facial development.
| S-EPMC7498679 | biostudies-literature
Project description:ChIP-seq of MOZ (Flag-V5-BIO tagged) in mouse mouse craniofacial development
| PRJNA555849 | ENA
Project description:Much of the bone, cartilage and smooth muscle of the vertebrate face is derived from neural crest (NC) cells. During craniofacial development, the anterior neural ridge (ANR) and olfactory pit (OP) signaling centers are responsible for driving the outgrowth, survival, and differentiation of NC populated facial prominences, primarily via FGF. While much is known about the functional importance of signaling centers, relatively little is understood of how these signaling centers are made and maintained. In this report we describe a dramatic craniofacial malformation in mice mutant for the zinc finger transcription factor gene Sp8. At E14.5 they show facial prominences that are reduced in size and underdeveloped, giving an almost faceless phenotype. At later times they show severe midline defects, excencephaly, hyperterlorism, cleft palate, and a striking loss of many NC and paraxial mesoderm derived cranial bones. Sp8 expression was primarily restricted to the ANR and OP regions during craniofacial development. Analysis of an extensive series of conditional Sp8 mutants confirmed the critical role of Sp8 in signaling centers, and not directly in the NC and paraxial mesoderm cells. The NC cells of the Sp8 mutants showed increased levels of apoptosis and decreased cell proliferation, thereby explaining the reduced sizes of the facial prominences. Perturbed gene expression in the Sp8 mutants was examined by laser capture microdissection coupled with microarrays, as well as in situ hybridization and immunostaining. The most dramatic differences included striking reductions in Fgf8 and Fgf17 expression in the ANR and OP signaling centers. We were also able to achieve genetic and pharmaceutical partial rescue of the Sp8 mutant phenotype by reducing Sonic Hedgehog (SHH) signaling. These results show that Sp8 primarily functions to promote Fgf expression in the ANR and OP signaling centers that drive the survival, proliferation, and differentiation of the NC and paraxial mesoderm that make the face.
| S-EPMC4078980 | biostudies-literature
Project description:The etiology and pathogenesis of craniofacial birth defects are multifactorial and include both genetic and environmental factors. Despite the identification of numerous genes associated with congenital craniofacial anomalies, our understanding of their etiology remains incomplete, and many affected individuals have an unknown genetic diagnosis. Here, we show that conditional loss of a Mediator complex subunit protein, Med23 in mouse neural crest cells (Med23fx/fx;Wnt1-Cre), results in micrognathia, glossoptosis, and cleft palate, mimicking the phenotype of Pierre Robin sequence. Sox9 messenger RNA and protein levels are both upregulated in neural crest cell-derived mesenchyme surrounding Meckel's cartilage and in the palatal shelves in Med23fx/fx;Wnt1-Cre mutant embryos compared to controls. Consistent with these observations, we demonstrate that Med23 binds to the promoter region of Sox9 and represses Sox9 expression in vitro. Interestingly, Sox9 binding to β-catenin is enhanced in Med23fx/fx;Wnt1-Cre mutant embryos, which, together with downregulation of Col2a1 and Wnt signaling target genes, results in decreased proliferation and altered jaw skeletal differentiation and cleft palate. Altogether, our data support a cell-autonomous requirement for Med23 in neural crest cells, potentially linking the global transcription machinery through Med23 to the etiology and pathogenesis of craniofacial anomalies such as micrognathia and cleft palate.
| S-EPMC7989139 | biostudies-literature
Project description:Trisomy 21 in humans causes cognitive impairment, craniofacial dysmorphology, and heart defects collectively referred to as Down syndrome. Yet, the pathophysiology of these phenotypes is not well understood. Craniofacial alterations may lead to complications in breathing, eating, and communication. Ts65Dn mice exhibit craniofacial alterations that model Down syndrome including a small mandible. We show that Ts65Dn embryos at 13.5 days gestation (E13.5) have a smaller mandibular precursor but a normal sized tongue as compared to euploid embryos, suggesting a relative instead of actual macroglossia originates during development. Neurological tissues were also altered in E13.5 trisomic embryos. Our array analysis found 155 differentially expressed non-trisomic genes in the trisomic E13.5 mandible, including 20 genes containing a homeobox DNA binding domain. Additionally, Sox9, important in skeletal formation and cell proliferation, was upregulated in Ts65Dn mandible precursors. Our results suggest trisomy causes altered expression of non-trisomic genes in development leading to structural changes associated with DS. Identification of genetic pathways disrupted by trisomy is an important step in proposing rational therapies at relevant time points to ameliorate craniofacial abnormalities in DS and other congenital disorders.
| S-EPMC3729611 | biostudies-literature
Project description:The specification of the skeletal muscle lineage during craniofacial development is dependent on the activity of MYF5 and MYOD, two members of the myogenic regulatory factor family. In the absence of MYF5 or MYOD there is not an overt muscle phenotype, whereas in the double Myf5;MyoD knockout branchiomeric myogenic precursors fail to be specified and skeletal muscle is not formed. The transcriptional regulation of Myf5 is controlled by a multitude of regulatory elements acting at different times and anatomical locations, with at least five operating in the branchial arches. By contrast, only two enhancers have been implicated in the regulation of MyoD. In this work, we characterize an enhancer element that drives Myf5 expression in the branchial arches from 9.5 days post-coitum and show that its activity in the context of the entire locus is dependent on two highly conserved E-boxes. These binding sites are required in a subset of Myf5-expressing cells including both progenitors and those which have entered the myogenic pathway. The correct levels of expression of Myf5 and MyoD result from activation by musculin and TCF21 through direct binding to specific enhancers. Consistent with this, we show that in the absence of musculin the timing of activation of Myf5 and MyoD is not affected but the expression levels are significantly reduced. Importantly, normal levels of Myf5 expression are restored at later stages, which might explain the absence of particular muscles in the Msc;Tcf21 double-knockout mice.
| S-EPMC3274357 | biostudies-literature