Birth Defects: Moebius Syndrome and Related Facial Weakness Disorders
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PROVIDER: PRJNA390828 | ENA |
REPOSITORIES: ENA
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Project description:Birth Defects: Moebius Syndrome and Related Facial Weakness Disorders
| PRJNA390829 | ENA
Project description:Molecular defects in pseudohypoparathyroidism or related disorders
| PRJNA89515 | ENA
Project description:Genetic Defects in familial renal disorders
| PRJNA89513 | ENA
Project description:Exposure to environmental teratogenic pollutant leads to severe birth defects. However, the biological events underlying these developmental abnormalities remain undefined. Here we report a molecular link between an environmental stress response pathway and key developmental genes during craniofacial development. In our study, we focused on the development of the facial prominences at E11.5. To do so, we compared the transcriptomes of mutant embryos (*Pax3Pax3-ERD/GFP *called DM in the microarray samples) to the one of control embryos (*Pax3GFP/+ *called GFP in the sample names). These are knock-in genetic models described in Bajard et al., 2006 and Relaix et al., 2005. In both of them a cassette coding for the GFP is replacing one allele of the Pax3 gene. The Pax3-ERD allele is a conditional one that drives the expression of the dominant negative form of Pax3 (Pax3-ERD) composed of the Pax3 DNA binding domain fused to the engrailed repressor domain (ERD) upon activation of a Cre recombinase. In this study, the Cre was driven by the zygote specific PGK enhancer. Strikingly, mutant mice with impaired Pax3/7 function display severe craniofacial defects. We show these are associated with an up-regulation of the signaling pathway mediated by the Aryl hydrocarbon Receptor (AhR), the receptor to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), revealing a genetic interaction between Pax3 and AhR signaling. Activation of AhR signaling in Pax3-deficient embryos drives facial mesenchymal cells out of the cell cycle through the up-regulation of p21 expression. Accordingly, inhibiting AhR activity rescues the cycling status of these cells and the facial closure of Pax3/7 mutants. Together, our findings demonstrate that the regulation of AhR signaling by Pax3/7 is required to protect against TCDD/AhR-mediated teratogenesis during craniofacial development.
2015-04-06 | E-MTAB-3238 | biostudies-arrayexpress
Project description:Kids First: Genomic Studies of Orofacial Cleft Birth Defects
| PRJNA329089 | ENA
Project description:To study the development of pig facial skin after birth, we use the facial skin tissues of healthy Chenghua sows as experimental materials. we then performed gene expression profiling analysis using data obtained from RNA-seq of pig facial skin tissues at four time points.
2023-05-10 | GSE231573 | GEO
Project description:In animal models, Nipbl-deficiency phenocopies gene expression changes and birth defects seen in Cornelia de Lange Syndrome (CdLS), the most common cause of which is Nipbl-haploinsufficiency. Previous studies in Nipbl+/- mice identified aberrant gene expression and heart defects as early as cardiac crescent (CC) stage. Here, we performed single-cell RNA-sequencing on wildtype (WT) and Nipbl+/- mouse embryos at CC- and earlier (gastrulation) stages. Nipbl+/- embryos had fewer mesoderm cells than WT and altered proportions of mesodermal cell subpopulations. These findings were associated with an underexpression of genes implicated in driving specific mesodermal lineages. Nipbl+/- embryos also misexpressed developmentally-critical genes, including the transcription factor, Nanog, and genes governing left-right and anterior-posterior patterning. These events of cell misallocation and transcriptional dysregulation foreshadowed defects in tissue composition and patterning that arise later in Nipbl+/- mice, offering insights into early developmental contributions to birth defects in CdLS.
2023-05-07 | GSE151589 | GEO
Project description:Kids First: Genomics of Orofacial Cleft Birth Defects in Latin American Families
| PRJNA397102 | ENA
Project description:<p>The Gabriella Miller Kids First Pediatric Research Program (<a href="https://www.commonfund.nih.gov/KidsFirst">Gabriella Miller Kids First Pediatric Research Program</a>) (Kids First) is a trans-NIH effort initiated in response to the <a href="https://www.govtrack.us/congress/bills/113/hr2019">2014 Gabriella Miller Kids First Research Act</a> and supported by the NIH Common Fund. This program focuses on gene discovery in pediatric cancers and structural birth defects and the development of the Gabriella Miller Kids First Pediatric Data Resource (Kids First Data Resource). Both, childhood cancers and structural birth defects are critical and costly conditions associated with substantial morbidity and mortality. Elucidating the underlying genetic etiology of these diseases has the potential to profoundly improve preventative measures, diagnostics, and therapeutic interventions.</p> <p>Whole Genome Sequence (WGS) and phenotypic data from this study are accessible through dbGaP and <a href="https://kidsfirstdrc.org">kidsfirstdrc.org</a>, where other Kids First datasets can also be accessed.</p> <p>Goals of this ongoing study are to identify novel "congenital cranial dysinnervation disorder" (CCDD) genes and define the role of the wildtype and mutant genes in normal and aberrant development. The umbrella term (CCDD) refers to congenital birth defects with malformation of one or more cranial nerves, typically resulting in limitations of eye and/or face movement. Examples of CCDDs include congenital fibrosis of the extraocular muscles (CFEOM), congenital ptosis, Duane retraction syndrome (DRS), horizontal gaze palsy with progressive scoliosis (HGPPS), congenital 3rd, 4th or 6th nerve palsies, Moebius syndrome (MBS), and hereditary congenital facial paresis (HCFP). In some cases, anosmia, and disorders of hearing, sucking, chewing, swallowing, and breathing may also be classified as CCDDs. CCDDs can be accompanied by additional birth defects such as intellectual and social disabilities, developmental delays, limb anomalies, and cardiac, GI, and GU disorders. The genetic basis of multiple CCDDs has been determined, and the gene mutations typically alter cranial motor neuron identity or function, or perturb axon growth and guidance. Despite these successes, the genetic etiologies of many inherited CCDDs remain unidentified. </p>
| phs001247 | dbGaP
Project description:Gabriella Miller Kids First Pediatric Research Project in Cornelia de Lange Syndrome, Related Diagnosis and Structural Birth Defects
| PRJNA671182 | ENA