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Active Notch Signaling is Required for Arm Regeneration ina Brittle Star

ABSTRACT: Cell signaling pathways play key roles to coordinate cellular events in development. Notch signaling pathway is highly conserved across all multicellular animals and is known to co- ordinate a multitude of diverse cellular events, including proliferation, differentiation, fate specification, and cell death. Specific functions of the pathway are however highly context- dependent and are not well characterized in post-traumatic regeneration. Here, we use a small-molecule inhibitor of the pathway (DAPT) to demonstrate that Notch signaling is required for proper arm regeneration in the brittle star Ophioderma brevispina, a highly re- generative member of the phylum Echinodermata. We also employ a transcriptome-wide gene expression analysis (RNA-seq) to characterize the downstream genes controlled by the Notch pathway in the brittle star regeneration.

ORGANISM(S): Ophioderma brevispina

PROVIDER: GSE142391 | GEO | 2019/12/20

REPOSITORIES: GEO

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Project description:Down-regulation of the Notch Differentiation Pathway in the Human Airway Epithelium in Normal Smokers and Smokers with Chronic Obstructive Lung Disease; In cigarette smokers, the toxic components of smoke place the epithelium under the constant stress of a variety of mechanisms of injury, with consequent modulation of airway epithelial regeneration and disordered differentiation. Based on the underlying hypothesis that these airway epithelial changes must involve quantitative changes in genes involved with the regulation of differentiation, we assessed the expression of the Notch pathway, a signaling pathway known to play a fundamental role in the embryonic lung as a gatekeeper for differentiation, in the small airway epithelium of non-smokers, normal smokers, and smokers with COPD. Microarray analysis demonstrated that 45 of the 55 Notch pathway-related genes are expressed in the human adult small airway epithelium and TaqMan quantitative PCR confirmed the expression of key genes in the pathway. TaqMan quantitative PCR analysis of the normal small airway epithelium demonstrated that Delta-like ligand 1 is the most highly expressed Notch ligand, Notch2 and 3 the most highly expressed receptor genes, and Hes1 the predominant downstream effector gene. TaqMan PCR was used to compare gene expression in nonsmokers vs healthy smokers vs smokers with COPD. The data show that some key genes in the ligands, receptors and downstream effectors in the Notch pathway are differentially expressed in smokers, with significant downregulation of a greater number of Notch-related genes in smokers with COPD compared to healthy smokers. These observations are consistent with the hypothesis that the Notch pathway, known to play an important role in lung morphogenesis, also likely plays a role in the adult human airway epithelium, with at least some of the Notch pathway gene expression dysregulated in association with smoking and its related disorder, COPD. Experiment Overall Design: Gene expression in airway epithelial cells of normal non-smokers.

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Active Notch Signaling is Required for Arm Regeneration ina Brittle Star

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