Background: Ageing, disease and malignant transformation of the skin are associated with changes in DNA methylation. So far, mostly invasive methodologies such as biopsies have been applied in collecting DNA methylation signatures. Tape stripping offers a noninvasive option for skin diagnostics.
View Article and Find Full Text PDFTranscription factors are key players in gene networks controlling cell fate specification during development. In multicellular organisms, they display complex patterns of expression and binding to their targets, hence, tissue specificity is required in the characterization of transcription factor-target interactions. We introduce here targeted DamID (TaDa) as a method for tissue-specific transcription factor target identification in intact animals.
View Article and Find Full Text PDFThe epidermis of Caenorhabditis elegans is an essential tissue for survival because it contributes to the formation of the cuticle barrier as well as facilitating developmental progression and animal growth. Most of the epidermis consists of the hyp7 hypodermal syncytium, the nuclei of which are largely generated by the seam cells, which exhibit stem cell-like behaviour during development. How seam cell progenitors differ transcriptionally from the differentiated hypodermis is poorly understood.
View Article and Find Full Text PDFIndividual cells and organisms experience perturbations from internal and external sources, yet manage to buffer these to produce consistent phenotypes, a property known as robustness. While phenotypic robustness has often been examined in unicellular organisms, it has not been sufficiently studied in multicellular animals. Here, we investigate phenotypic robustness in seam cells.
View Article and Find Full Text PDFA fundamental question in medical genetics is how the genetic background modifies the phenotypic outcome of mutations. We address this question by focusing on the seam cells, which display stem cell properties in the epidermis of Caenorhabditis elegans. We demonstrate that a putative null mutation in the GATA transcription factor egl-18, which is involved in seam cell fate maintenance, is more tolerated in the CB4856 isolate from Hawaii than the lab reference strain N2 from Bristol.
View Article and Find Full Text PDFPopulations often display consistent developmental phenotypes across individuals despite inevitable biological stochasticity. Nevertheless, developmental robustness has limits, and systems can fail upon change in the environment or the genetic background. We use here the seam cells, a population of epidermal stem cells in , to study the influence of temperature change and genetic variation on cell fate.
View Article and Find Full Text PDFBiological systems are subject to inherent stochasticity. Nevertheless, development is remarkably robust, ensuring the consistency of key phenotypic traits such as correct cell numbers in a certain tissue. It is currently unclear which genes modulate phenotypic variability, what their relationship is to core components of developmental gene networks, and what is the developmental basis of variable phenotypes.
View Article and Find Full Text PDFGene drive systems that enable super-Mendelian inheritance of a transgene have the potential to modify insect populations over a timeframe of a few years. We describe CRISPR-Cas9 endonuclease constructs that function as gene drive systems in Anopheles gambiae, the main vector for malaria. We identified three genes (AGAP005958, AGAP011377 and AGAP007280) that confer a recessive female-sterility phenotype upon disruption, and inserted into each locus CRISPR-Cas9 gene drive constructs designed to target and edit each gene.
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