Explore the vast range of titles available.

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. We established a zebrafish in vivo model to study the underlying mechanisms and to identify pharmacological agents that may be developed into therapeutics. Both adult and larval zebrafish displayed signs of paclitaxel neurotoxicity, including sensory axon degeneration and the loss of touch response in the distal caudal fin. Intriguingly, studies in zebrafish larvae showed that paclitaxel rapidly promotes epithelial damage and decreased mechanical stress resistance of the skin before induction of axon degeneration. Moreover, injured paclitaxel-treated zebrafish skin and scratch-wounded human keratinocytes (HEK001) display reduced healing capacity. Epithelial damage correlated with rapid accumulation of fluorescein-conjugated paclitaxel in epidermal basal keratinocytes, but not axons, and upregulation of matrix-metalloproteinase 13 (MMP-13, collagenase 3) in the skin. Pharmacological inhibition of MMP-13, in contrast, largely rescued paclitaxel-induced epithelial damage and neurotoxicity, whereas MMP-13 overexpression in zebrafish embryos rendered the skin vulnerable to injury under mechanical stress conditions. Thus, our studies provide evidence that the epidermis plays a critical role in this condition, and we provide a previously unidentified candidate for therapeutic interventions.

Teleost fishes and urodele amphibians can regenerate amputated appendages, whereas this ability is restricted to digit tips in adult mammals. One key component of appendage regeneration is reinnervation of the wound area. However, how innervation is regulated in injured appendages of adult vertebrates has seen limited research attention. From a forward genetics screen for temperature-sensitive defects in zebrafish fin regeneration, we identified a mutation that disrupted regeneration while also inducing paralysis at the restrictive temperature. Genetic mapping and complementation tests identify a mutation in the major neuronal voltage-gated sodium channel (VGSC) gene scn8ab. Conditional disruption of scn8ab impairs early regenerative events, including blastema formation, but does not affect morphogenesis of established regenerates. Whereas scn8ab mutations reduced neural activity as expected, they also disrupted axon regrowth and patterning in fin regenerates, resulting in hypoinnervation. Our findings indicate that the activity of VGSCs plays a proregenerative role by promoting innervation of appendage stumps.

Functional recovery from cutaneous injury requires not only the healing and regeneration of skin cells but also reinnervation of the skin by somatosensory peripheral axon endings. To investigate how sensory axon regeneration and wound healing are coordinated, we amputated the caudal fins of zebrafish larvae and imaged somatosensory axon behavior. Fin amputation strongly promoted the regeneration of nearby sensory axons, an effect that could be mimicked by ablating a few keratinocytes anywhere in the body. Since injury produces the reactive oxygen species hydrogen peroxide (H(2)O(2)) near wounds, we tested whether H(2)O(2) influences cutaneous axon regeneration. Exposure of zebrafish larvae to sublethal levels of exogenous H(2)O(2) promoted growth of severed axons in the absence of keratinocyte injury, and inhibiting H(2)O(2) production blocked the axon growth-promoting effects of fin amputation and keratinocyte ablation. Thus, H(2)O(2) signaling helps coordinate wound healing with peripheral sensory axon reinnervation of the skin.

Background Zebrafish are able to regenerate many of its tissues and organs after damage. In amphibians this process is regulated by nerve fibres present at the site of injury, which have been proposed to release factors into the amputated limbs/fins, promoting and sustaining the proliferation of blastemal cells. Although some candidate factors have been proposed to mediate the nerve dependency of regeneration, the molecular mechanisms involved in this process remain unclear. Results We have used zebrafish as a model system to address the role of nerve fibres in fin regeneration. We have developed a protocol for pectoral fin denervation followed by amputation and analysed the regenerative process under this experimental conditions. Upon denervation fins were able to close the wound and form a wound epidermis, but could not establish a functional apical epithelial cap, with a posterior failure of blastema formation and outgrowth, and the accumulation of several defects. The expression patterns of genes known to be key players during fin regeneration were altered upon denervation, suggesting that nerves can contribute to the regulation of the Fgf, Wnt and Shh pathways during zebrafish fin regeneration. Conclusions Our results demonstrate that proper innervation of the zebrafish pectoral fin is essential for a successful regenerative process, and establish this organism as a useful model to understand the molecular and cellular mechanisms of nerve dependence, during vertebrate regeneration.

A wide variety of rudimentary and apparently non-functional traits have persisted over extended evolutionary time. Recent evidence has shown that some of these traits may be maintained as a result of developmental constraints or neutral energetic cost, but for others their true function was not recognized. The adipose fin is small, fleshy, non-rayed and located between the dorsal and caudal fins on eight orders of basal teleosts and has traditionally been regarded as vestigial without clear function. We describe here the ultrastructure of the adipose fin and for the first time, to our knowledge, present evidence of extensive nervous tissue, as well as an unusual subdermal complex of interconnected astrocyte-like cells equipped with primary cilia. The fin contains neither adipose tissue nor fin rays. Many fusiform actinotrichia, comprising dense striated macrofibrils, support the free edge and connect with collagen cables that link the two sides. These results are consistent with a recent hypothesis that the adipose fin may act as a precaudal flow sensor, where its removal can be detrimental to swimming efficiency in turbulent water. Our findings provide insight to the broader themes of function versus constraints in evolutionary biology and may have significance for fisheries science, as the adipose fin is routinely removed from millions of salmonids each year.

The activity of ion channels and transporters generates ion-specific fluxes that encode electrical and/or chemical signals with biological significance. Even though it is long known that some of those signals are crucial for regeneration, only in recent years the corresponding molecular sources started to be identified using mainly invertebrate or larval vertebrate models. We used adult zebrafish caudal fin as a model to investigate which and how ion transporters affect regeneration in an adult vertebrate model. Through the combined use of biophysical and molecular approaches, we show that V-ATPase activity contributes to a regeneration-specific H+ ef`flux. The onset and intensity of both V-ATPase expression and H+ efflux correlate with the different regeneration rate along the proximal-distal axis. Moreover, we show that V-ATPase inhibition impairs regeneration in adult vertebrate. Notably, the activity of this H+ pump is necessary for aldh1a2 and mkp3 expression, blastema cell proliferation and fin innervation. To the best of our knowledge, this is the first report on the role of V-ATPase during adult vertebrate regeneration.

Motor innervation to the tetrapod forelimb and fish pectoral fin is assumed to share a conserved spinal cord origin, despite major structural and functional innovations of the appendage during the vertebrate water-to-land transition. In this paper, we present anatomical and embryological evidence showing that pectoral motoneurons also originate in the hindbrain among ray-finned fish. New and previous data for lobe-finned fish, a group that includes tetrapods, and more basal cartilaginous fish showed pectoral innervation that was consistent with a hindbrain-spinal origin of motoneurons. Together, these findings support a hindbrain–spinal phenotype as the ancestral vertebrate condition that originated as a postural adaptation for pectoral control of head orientation. A phylogenetic analysis indicated that Hox gene modules were shared in fish and tetrapod pectoral systems. We propose that evolutionary shifts in Hox gene expression along the body axis provided a transcriptional mechanism allowing eventual decoupling of pectoral motoneurons from the hindbrain much like their target appendage gained independence from the head. It was previously thought that the nerves in the pectoral fin of fish came solely from the spinal cord. Here, motoneurons in ray-finned fish are shown to also originate from the hindbrain, demonstrating that innervation was from both the hindbrain and the spinal cord in ancesteral vertebrates.

Blind Mexican cave fish (Astyanax fasciatus) lack a functional visual system and have been shown to sense their environment using a technique called hydrodynamic imaging, whereby nearby objects are detected by sensing distortions in the flow field of water around the body using the mechanosensory lateral line. This species has also been noted to touch obstacles, mainly with the pectoral fins, apparently using this tactile information alongside hydrodynamic imaging to sense their surroundings. This study aimed to determine the relative contributions of hydrodynamic and tactile information during wall following behaviour in blind Mexican cave fish. A wall was custom built with a ‘netted' region in its centre, which provided very similar tactile information to a solid tank wall, but was undetectable using hydrodynamic imaging. The fish swam significantly closer to and collided more frequently with the netted region of this wall than the solid regions, indicating that the fish did not perceive the netted region as a solid obstacle despite being able to feel it as such with their pectoral fins. We conclude that the touching of objects with the pectoral fins may be an artefact of the intrinsic link between pectoral fin extensions and tail beating whilst swimming, and does not function to gather information. During wall following, hydrodynamic information appears to be used strongly in preference to tactile information in this non-visual system.

In stock enhancement and sea-ranching procedures, the adipose fin of hundreds of millions of salmonids is removed for marking purposes annually. However, recent studies proved the significance of the adipose fin as a flow sensor and attraction feature. In the present study, we profiled the specific expression of 20 neuron- and glial cell-marker genes in the adipose fin and seven other tissues (including dorsal and pectoral fin, brain, skin, muscle, head kidney, and liver) of the salmonid species rainbow trout Oncorhynchus mykiss and maraena whitefish Coregonus maraena. Moreover, we measured the transcript abundance of genes coding for 15 mechanoreceptive channel proteins from a variety of mechanoreceptors known in vertebrates. The overall expression patterns indicate the presence of the entire repertoire of neurons, glial cells and receptor proteins on the RNA level. This quantification suggests that the adipose fin contains considerable amounts of small nerve fibers with unmyelinated or slightly myelinated axons and most likely mechanoreceptive potential. The findings are consistent for both rainbow trout and maraena whitefish and support a previous hypothesis about the innervation and potential flow sensory function of the adipose fin. Moreover, our data suggest that the resection of the adipose fin has a stronger impact on the welfare of salmonid fish than previously assumed.

Adipose fins are found on approximately 20% of ray-finned fish species. The apparently rudimentary anatomy of adipose fins inspired a longstanding hypothesis that these fins are vestigial and lack function. However, adipose fins have evolved repeatedly within Teleostei, suggesting adaptive function. Recently, adipose fins were proposed to function as mechanosensors, detecting fluid flow anterior to the caudal fin. Here we test the hypothesis that adipose fins are mechanosensitive in the catfish Corydoras aeneus. Neural activity, recorded from nerves that innervate the fin, was shown to encode information on both movement and position of the fin membrane, including the magnitude of fin membrane displacement. Thus, the adipose fin of C. aeneus is mechanosensitive and has the capacity to function as a 'precaudal flow sensor'. These data force reevaluation of adipose fin clipping, a common strategy for tagging fishes, and inform hypotheses of how function evolves in novel vertebrate appendages.