Reducing translation through eIF4G/IFG-1 improves survival under ER stress that depends on heat shock factor HSF-1 in Caenorhabditis elegans.

Although certain methods of lowering and/or altering mRNA translation are associated with increased lifespan, the mechanisms underlying this effect remain largely unknown. We previously showed that the increased lifespan conferred by reducing expression of eukaryotic translation initiation factor 4G (eIF4G/IFG-1) enhances survival under starvation conditions while shifting protein expression toward factors involved with maintaining ER-dependent protein and lipid balance. In this study, we investigated changes in ER homeostasis and found that lower eIF4G/IFG-1 increased survival under conditions of ER stress.

Cortisol-treated zebrafish embryos develop into pro-inflammatory adults with aberrant immune gene regulation.

Chronic early-life stress increases adult susceptibility to numerous health problems linked to chronic inflammation. One way that this may occur is via glucocorticoid-induced developmental programming. To gain insight into such programming we treated zebrafish embryos with cortisol and examined the effects on both larvae and adults.

A Conserved MicroRNA Regulatory Circuit Is Differentially Controlled during Limb/Appendage Regeneration.

Background: Although regenerative capacity is evident throughout the animal kingdom, it is not equally distributed throughout evolution. For instance, complex limb/appendage regeneration is muted in mammals but enhanced in amphibians and teleosts. The defining characteristic of limb/appendage regenerative systems is the formation of a dedifferentiated tissue, termed blastema, which serves as the progenitor reservoir for regenerating tissues.

Paclitaxel-induced epithelial damage and ectopic MMP-13 expression promotes neurotoxicity in zebrafish.

Paclitaxel is a microtubule-stabilizing chemotherapeutic agent that is widely used in cancer treatment and in a number of curative and palliative regimens. Despite its beneficial effects on cancer, paclitaxel also damages healthy tissues, most prominently the peripheral sensory nervous system. The mechanisms leading to paclitaxel-induced peripheral neuropathy remain elusive, and therapies that prevent or alleviate this condition are not available.

Comparative transcriptomic profiling of hydrogen peroxide signaling networks in zebrafish and human keratinocytes: Implications toward conservation, migration and wound healing.

Skin wounds need to be repaired rapidly after injury to restore proper skin barrier function. Hydrogen peroxide (H2O2) is a conserved signaling factor that has been shown to promote a variety of skin wound repair processes, including immune cell migration, angiogenesis and sensory axon repair. Despite growing research on H2O2 functions in wound repair, the downstream signaling pathways activated by this reactive oxygen species in the context of injury remain largely unknown.

Dynamic microRNA-101a and Fosab expression controls zebrafish heart regeneration.

Cardiovascular disease is the leading cause of morbidity and mortality in the Western world owing to the limited regenerative capacity of the mammalian cardiovascular system. In lieu of new muscle synthesis, the human heart replaces necrotic tissue with deposition of a noncontractile scar. By contrast, the adult zebrafish is endowed with a remarkable regenerative capacity, capable of de novo cardiomyocyte (CM) creation and scar tissue removal when challenged with an acute injury.

A Uniform System for the Annotation of Vertebrate microRNA Genes and the Evolution of the Human microRNAome.

Although microRNAs (miRNAs) are among the most intensively studied molecules of the past 20 years, determining what is and what is not a miRNA has not been straightforward. Here, we present a uniform system for the annotation and nomenclature of miRNA genes. We show that less than a third of the 1,881 human miRBase entries, and only approximately 16% of the 7,095 metazoan miRBase entries, are robustly supported as miRNA genes.

Transient laminin beta 1a Induction Defines the Wound Epidermis during Zebrafish Fin Regeneration.

The first critical stage in salamander or teleost appendage regeneration is creation of a specialized epidermis that instructs growth from underlying stump tissue. Here, we performed a forward genetic screen for mutations that impair this process in amputated zebrafish fins. Positional cloning and complementation assays identified a temperature-sensitive allele of the ECM component laminin beta 1a (lamb1a) that blocks fin regeneration.

A Forward Genetic Screen for Suppressors of Somatic P Granules in Caenorhabditis elegans.

In Caenorhabditis elegans, germline expression programs are actively repressed in somatic tissue by components of the synMuv (synthetic multi-vulva) B chromatin remodeling complex, which include homologs of tumor suppressors Retinoblastoma (Rb/LIN-35) and Malignant Brain Tumor (MBT/LIN-61). However, the full scope of pathways that suppress germline expression in the soma is unknown. To address this, we performed a mutagenesis and screened for somatic expression of GFP-tagged PGL-1, a core P-granule nucleating protein.

CSR-1 and P granules suppress sperm-specific transcription in the C. elegans germline.

Germ granules (P granules) in C. elegans are required for fertility and function to maintain germ cell identity and pluripotency. Sterility in the absence of P granules is often accompanied by the misexpression of soma-specific proteins and the initiation of somatic differentiation in germ cells.

Capturing tissue repair in zebrafish larvae with time-lapse brightfield stereomicroscopy.

The zebrafish larval tail fin is ideal for studying tissue regeneration due to the simple architecture of the larval fin-fold, which comprises of two layers of skin that enclose undifferentiated mesenchyme, and because the larval tail fin regenerates rapidly within 2-3 days. Using this system, we demonstrate a method for capturing the repair dynamics of the amputated tail fin with time-lapse video brightfield stereomicroscopy. We demonstrate that fin amputation triggers a contraction of the amputation wound and extrusion of cells around the wound margin, leading to their subsequent clearance.

Germ-granule components prevent somatic development in the C. elegans germline.

Specialized ribonucleoprotein organelles collectively known as germ granules are found in the germline cytoplasm from worms to humans [1]. In Drosophila, germ granules have been implicated in germline determination [2]. C.

Role of translation initiation factor 4G in lifespan regulation and age-related health.

Inhibiting expression of eukaryotic translation initiation factor 4G (eIF4G) arrests normal development but extends lifespan when suppressed during adulthood. In addition to reducing overall translation, inhibition alters the stoichiometry of mRNA translation in favor of genes important for responding to stress and against those associated with growth and reproduction in C. elegans.

Rhythmic Ca²⁺ signaling: keeping time with microRNAs.

Pacemaker cells are specialized cell types that drive biological rhythms like the heartbeat and intestinal peristalsis. What determines whether a cell functions as a pacemaker? Studies in Caenorhabditis elegans suggest that pacemaking activity may be controlled in part by microRNAs.

A natural deletion of the HoxC cluster in elasmobranch fishes.

Hox proteins are a metazoan-specific family of transcription factors that are required for developmental patterning. The genomic arrangement of Hox genes into four paralogous clusters is a primitive feature of jawed vertebrates. By using high-throughput sequencing, we demonstrate the absence of all HoxC transcripts from embryos of the shark Scyliorhinus canicula and the skate Leucoraja erinacea and the absence of all HoxC genes and two HoxC-associated microRNAs from the genome of L.