Influence of Mpv17 on hair-cell mitochondrial homeostasis, synapse integrity, and vulnerability to damage in the zebrafish lateral line

Noise exposure is particularly stressful to hair-cell mitochondria, which must produce enough energy to meet high metabolic demands as well as regulate local intracellular C

Using the zebrafish lateral line to understand the roles of mitochondria in sensorineural hearing loss

Hair cells are the mechanosensory receptors of the inner ear and can be damaged by noise, aging, and ototoxic drugs. This damage often results in permanent sensorineural hearing loss. Hair cells have high energy demands and rely on mitochondria to produce ATP as well as contribute to intracellular calcium homeostasis. In addition to generating ATP, mitochondria produce reactive oxygen species, which can lead to oxidative stress, and regulate cell death pathways. Zebrafish lateral-line hair cells are structurally and functionally analogous to cochlear hair cells but are optically and pharmacologically accessible within an intact specimen, making the zebrafish a good model in which to study hair-cell mitochondrial activity. Moreover, the ease of genetic manipulation of zebrafish embryos allows for the study of mutations implicated in human deafness, as well as the generation of transgenic models to visualize mitochondrial calcium transients and mitochondrial activity in live organisms. Studies of the zebrafish lateral line have shown that variations in mitochondrial activity can predict hair-cell susceptibility to damage by aminoglycosides or noise exposure. In addition, antioxidants have been shown to protect against noise trauma and ototoxic drug-induced hair-cell death. In this review, we discuss the tools and findings of recent investigations into zebrafish hair-cell mitochondria and their involvement in cellular processes, both under homeostatic conditions and in response to noise or ototoxic drugs. The zebrafish lateral line is a valuable model in which to study the roles of mitochondria in hair-cell pathologies and to develop therapeutic strategies to prevent sensorineural hearing loss in humans

The Nature Press, Vol. 3

Nature News was a newsletter publication about activities at the Cheadle Center for Biodiveristy and Ecological Restoration

Whole genome sequencing-based mapping and candidate identification of mutations from fixed zebrafish tissue

As forward genetic screens in zebrafish become more common, the number of mutants that cannot be identified by gross morphology or through transgenic approaches, such as many nervous system defects, has also increased. Screening for these difficult-to-visualize phenotypes demands techniques such as whole-mount in situ hybridization (WISH) or antibody staining, which require tissue fixation. To date, fixed tissue has not been amenable for generating libraries for whole genome sequencing (WGS). Here, we describe a method for using genomic DNA from fixed tissue and a bioinformatics suite for WGS-based mapping of zebrafish mutants. We tested our protocol using two known zebrafish mutant alleles, gpr126st49 and egr2bfh227, both of which cause myelin defects. As further proof of concept we mapped a novel mutation, stl64, identified in a zebrafish WISH screen for myelination defects. We linked stl64 to chromosome 1 and identified a candidate nonsense mutation in the F-box and WD repeat domain containing 7 (fbxw7) gene. Importantly, stl64 mutants phenocopy previously described fbxw7vu56 mutants, and knockdown of fbxw7 in wild-type animals produced similar defects, demonstrating that stl64 disrupts fbxw7. Together, these data show that our mapping protocol can map and identify causative lesions in mutant screens that require tissue fixation for phenotypic analysis

Mechanical overstimulation causes acute injury and synapse loss followed by fast recovery in lateral-line neuromasts of larval zebrafish

Excess noise damages sensory hair cells, resulting in loss of synaptic connections with auditory nerves and, in some cases, hair-cell death. The cellular mechanisms underlying mechanically induced hair-cell damage and subsequent repair are not completely understood. Hair cells in neuromasts of larval zebrafish are structurally and functionally comparable to mammalian hair cells but undergo robust regeneration following ototoxic damage. We therefore developed a model for mechanically induced hair-cell damage in this highly tractable system. Free swimming larvae exposed to strong water wave stimulus for 2 hr displayed mechanical injury to neuromasts, including afferent neurite retraction, damaged hair bundles, and reduced mechanotransduction. Synapse loss was observed in apparently intact exposed neuromasts, and this loss was exacerbated by inhibiting glutamate uptake. Mechanical damage also elicited an inflammatory response and macrophage recruitment. Remarkably, neuromast hair-cell morphology and mechanotransduction recovered within hours following exposure, suggesting severely damaged neuromasts undergo repair. Our results indicate functional changes and synapse loss in mechanically damaged lateral-line neuromasts that share key features of damage observed in noise-exposed mammalian ear. Yet, unlike the mammalian ear, mechanical damage to neuromasts is rapidly reversible

The Nature News, Vol. 2

Nature News was a newsletter publication about activities at the Cheadle Center for Biodiveristy and Ecological Restoration

The Nature News, Vol. 2

Nature News was a newsletter publication about activities at the Cheadle Center for Biodiveristy and Ecological Restoration

The Nature Press, Vol. 3

Nature News was a newsletter publication about activities at the Cheadle Center for Biodiveristy and Ecological Restoration

Century-to-millennial scale climatic variability in Lake Malawi revealed by isotope records

Diatom-based oxygen isotope data (δ18Odiatom) from Lake Malawi show multi-centennial scale wet–dry intervals spaced approximately every 2.3 ka throughout a 25 ka sequence. The δ18Odiatom record is supported by a lower resolution deuterium (δDpa)isotope curve derived from palmitic acid. We interpret these isotope data in terms of major shifts in precipitation and evaporation moderated by seasonal controls on the host organisms. Dry periods marked by relatively positive isotope values, represent the extension of abrupt Holocene events noted from northern and equatorial Africa to 10–15°S. These events in Lake Malawi correspond to cool episodes in Greenland, thereby demonstrating teleconnections generated by meridional temperature gradients. Sea surface temperatures are likely to be the primary transmitter of deglacial climate changes, although trade wind strength and direction is critical in controlling precipitation patterns in tropical regions. Conversely, the global hydrological cycle, driven by low latitude regions represents an important positive feedback amplifying deglacial processes