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The mechanosensory (lateral line) and electrosensory systems are two important non-visual sensory modalities, especially in low light environments. Despite their importance, these sensory systems have received little attention in deepwater chondrichthyans. Here, we describe the morphological organisation of the peripheral lateral line and electrosensory systems in two species of chimaeras; the pale ghost shark Hydrolagus bemisi (Chimaeridae) and the Australasia narrow-nosed spookfish Harriotta avia (Rhinochimaeridae), occupying depth ranges of 400–1,100 m and 260–1,278 m, respectively. Using topographic mapping, computed tomography, histology, and scanning electron microscopy, the distribution, abundance, size, and microstructure of lateral line grooves and organs (neuromasts), and ampullary organs (pores, canals, and bulbs) are described. The arrangement of the peripheral sense organs in both these systems may reflect comparable feeding strategies for detecting benthic prey. While the elongated rostrum of Harriotta avia is likely used as a sensory probe, providing spatially-resolved information about minute hydrodynamic disturbances and electric fields of potential prey beneath the animal, the arrangement of sense organs in Hydrolagus bemisi indicates that this species may rely less on electroreception. The study compares the morphology and provides information on the relative importance of two (non-visual) sensory modalities in two demersal holocephalans that remain vulnerable to anthropogenic disturbances.

Analysis of mechanotransduction among ensembles of sensory hair cells in vivo is challenging in many species. To overcome this challenge, we used optical indicators to investigate mechanotransduction among collections of hair cells in intact zebrafish. Our imaging reveals a previously undiscovered disconnect between hair-cell mechanosensation and synaptic transmission. We show that saturating mechanical stimuli able to open mechanically gated channels are unexpectedly insufficient to evoke vesicle fusion in the majority of hair cells. Although synaptically silent, latent hair cells can be rapidly recruited after damage, demonstrating that they are synaptically competent. Therefore synaptically silent hair cells may be an important reserve that acts to maintain sensory function. Our results demonstrate a previously unidentified level of complexity in sculpting sensory transmission from the periphery. Hair cells of the inner ear are mechanosensors that detect sound, and synapse onto afferent neurons. Here, the authors used calcium imaging to find that not all hair cells are synaptically engaged, but after damage these silent cells are synaptically engaged.

Wnt and FGF are highly conserved signaling pathways found in various organs and have been identified as important regulators of auditory organ development. In this study, we used the zebrafish lateral line system to study the cooperative roles of the Wnt and FGF pathways in regulating progenitor cell proliferation and regenerative cell proliferation. We found that activation of Wnt signaling induced cell proliferation and increased the number of hair cells in both developing and regenerating neuromasts. We further demonstrated that FGF signaling was critically involved in Wnt-regulated proliferation, and inhibition of FGF abolished the Wnt stimulation-mediated effects on cell proliferation, while activating FGF signaling with basic fibroblast growth factor (bFGF) led to a partial rescue of the proliferative failure and hair cell defects in the absence of Wnt activity. Whole-mount in situ hybridization analysis showed that the expression of several FGF pathway genes, including pea3 and fgfr1 , was increased in neuromasts after treatment with the Wnt pathway inducer BIO. Interestingly, when SU5402 was used to inhibit FGF signaling, neuromast cells expressed much lower levels of the FGF receptor gene, fgfr1 , but produced increased levels of Wnt target genes, including ctnnb1 , ctnnb2 , and tcf7l2 , while bFGF treatment produced no alterations in the expression of those genes, suggesting that fgfr1 might restrict Wnt signaling in neuromasts during proliferation. In summary, our analysis demonstrates that both the Wnt and FGF pathways are tightly integrated to modulate the proliferation of progenitor cells during early neuromast development and regenerative cell proliferation after neomycin-induced injury in the zebrafish neuromast. Sensory cells: Hearing lessons from signals in fish Studying sensory organs on the skin of zebrafish is revealing details of molecular signaling pathways that may be relevant to our own sensory systems, especially the hair cells of the ear. These cells have fine hair-like structures that move in response to sound waves and help generate electrical signals to the brain that result in perception of sound. Huawei Li and colleagues at Fudan University, Shanghai, China, studied the roles of two well-known cellular signaling pathways in regulating the proliferation of similar sensory hair cells in zebrafish, a commonly used model organism. These pathways involve cell surface proteins that interact with small extracellular molecules to stimulate molecular changes within cells. Learning how the pathways control hair cell generation and multiplication may assist modification of similar systems in humans to study and treat hearing loss.

The lateral line system enables fishes and aquatic-stage amphibians to detect local water movement via mechanosensory hair cells in neuromasts, and many species to detect weak electric fields via electroreceptors (modified hair cells) in ampullary organs. Both neuromasts and ampullary organs develop from lateral line placodes, but the molecular mechanisms underpinning ampullary organ formation are understudied relative to neuromasts. This is because the ancestral lineages of zebrafish (teleosts) and Xenopus (frogs) independently lost electroreception. We identified Bmp5 as a promising candidate via differential RNA-seq in an electroreceptive ray-finned fish, the Mississippi paddlefish ( Polyodon spathula ; Modrell et al., 2017, eLife 6: e24197). In an experimentally tractable relative, the sterlet sturgeon ( Acipenser ruthenus ), we found that Bmp5 and four other Bmp pathway genes are expressed in the developing lateral line, and that Bmp signalling is active. Furthermore, CRISPR/Cas9-mediated mutagenesis targeting Bmp5 in G0-injected sterlet embryos resulted in fewer ampullary organs. Conversely, when Bmp signalling was inhibited by DMH1 treatment shortly before the formation of ampullary organ primordia, supernumerary ampullary organs developed. These data suggest that Bmp5 promotes ampullary organ development, whereas Bmp signalling via another ligand(s) prevents their overproduction. Taken together, this demonstrates opposing roles for Bmp signalling during ampullary organ formation.

Like the sensory organs of the human inner ear, the lateral-line neuromasts (NMs) of fish such as the zebrafish ( Danio rerio ) contain mechanosensory hair cells (HCs) that are surrounded by supporting cells (SCs). A damaged NM can quickly regenerate new HCs by expressing genes such as atoh1a , the master regulator of HC fate, in the SCs at the NM’s center. We used the supervised learning algorithm DELAY to infer the early gene-regulatory network for regenerating central SCs and HCs and identified adaptations that promote the rapid regeneration of lateral-line HCs in larval zebrafish. The top hub in the network, Y-box binding protein 1 ( ybx1 ), is highly expressed in HC progenitors and young HCs and its protein can recognize DNA-binding motifs in cyprinids’ candidate regeneration-responsive promoter element for atoh1a . We showed that NMs from ybx1 mutant zebrafish larvae display consistent, regeneration-specific deficits in HC number and initiate both HC regeneration and atoh1a expression 20% slower than in wild-type siblings. By demonstrating that ybx1 promotes rapid HC regeneration through early atoh1a upregulation, the results support DELAY’s ability to identify key temporal regulators of gene expression.

The lateral line system is a mechanosensory organ found in all fish species and located on the skin or in subdermal canals. The basic functional units are superficial and canal neuromasts, which are involved in hydrodynamic sensing and cohesion in schooling fish. Yellow-eyed mullet ( Aldrichetta forsteri ) are an obligate schooling species found commonly in shallow coastal areas of New Zealand and Australia. Schooling is a fundamental part of their behavioural repertoire, yet little is known about the structure or functionality of the lateral line in this species. We used scanning electron microscopy to characterise the morphology of trunk superficial neuromasts. We then took a multi-sensory approach and conducted behavioural experiments comparing school structure in groups of fish with and without fully functioning lateral lines, under photopic and scotopic conditions. A highly developed hydro-sensing system exists on the trunk of yellow-eyed mullet consisting of superficial neuromasts containing hundreds of hair cells aligned, with respect to their most sensitive axis, in a rostrocaudal direction. Without functioning superficial neuromasts, schooling behaviour was disrupted under both photopic and scotopic conditions and the ability to detect stationary objects decreased. Results highlight the importance of this component of the lateral line system to schooling behaviour.

Bioengineering, which studies the principles and design of biological systems, is a field that has inspired the development of several technologies that are currently in use. In this work, we use concepts from the fish lateral line sensing mechanism and apply them to seismic imaging processing. The lateral line is a sensory system composed of an integrated array of mechanical sensors spanning along the fish body. We compare the array of sensors along body fish with the seismic acquisition, which employs an array of equally spaced identical mechanical sensors to image the Earth's subsurface. In both situations, the mechanical sensors capture and process mechanical vibrations from the environment to produce useful information. We explore the strategy of using the low-pass and high-pass sensors schema of fish lateral line to improve the seismic technique. We use the full-wave inversion method to compare the conventional acquisition procedure of identical sensors with alternative sets of different sensors, which mimics the fish lateral line. Our results show that the alternate sensors arrangement surpasses the performance of the conventional acquisition method, using just half of the input information. The results point at an image processing technique that is computationally more efficient and economical than the usual seismic processing method.

Krüpple-like factors (Klfs) are highly conserved zinc-finger transcription factors that regulate various developmental processes, such as haematopoiesis and cardiovascular development. In zebrafish, transient knockdown analysis of biklf / klf17 using antisense morpholino suggests the involvement of biklf / klf17 in primitive erythropoiesis and hatching gland development; however, the continuous physiological importance of klf17 remains uncharacterized under the genetic ablation of the klf17 gene among vertebrates. We established the klf17 -disrupted zebrafish lines using the CRISPR/Cas9 technology and performed phenotypic analysis throughout early embryogenesis. We found that the klf17 -deficient embryos exhibited abnormal lateral line neuromast deposition, whereas the production of primitive erythrocytes and haemoglobin production were observed in the klf17 -deficient embryos. The expression of lateral line neuromast genes, klf17 and s100t , in the klf17 -deficient embryos was detected in posterior lateral line neuromasts abnormally positioned at short intervals. Furthermore, the klf17 -deficient embryos failed to hatch and died without hatching around 15 days post-fertilization (dpf), whereas the dechorionated klf17 -deficient embryos and wild-type embryos were alive at 15 dpf. The klf17 -deficient embryos abolished hatching gland cells and Ctsl1b protein expression, and eliminated the expression of polster and hatching gland marker genes, he1 . 1 , ctsl1b and cd63 . Thus, the klf17 gene plays important roles in posterior lateral line neuromast and hatching gland development.

Aim: The present review aimed to consolidate and analyze the recent information about the use of zebrafish in studies concerning cisplatin-induced ototoxicity and otoprotection. Material and methods: The PubMed, Web of Science, and Scopus databanks were searched using the following MESH terms: zebrafish, cisplatin, ototoxicity. The identified publications were screened according to inclusion and exclusion criteria and the 26 qualifying manuscripts were included in the full-text analysis. The experimental protocols, including cisplatin concentrations, the exposure duration and the outcome measurements used in zebrafish larvae studies, were evaluated and the reported knowledge was summarized. Results: Twenty-six substances protecting from cisplatin-induced toxicity were identified with the use of zebrafish larvae. These substances include quinine, salvianolic acid B, berbamine 6, benzamil, quercetin, dexmedetomidine, dexamethsanone, quinoxaline, edaravone, apocynin, dimethyl sulfoxide, KR-22335, SRT1720, ORC-13661, 3-MA, D-methionine, mdivi-1, FUT-175, rapamycin, Z-LLF-CHO, ATX, NAC, CYM-5478, CHCP1, CHCP2 and leupeptin. The otoprotective effects of compounds were attributed to their anti-ROS, anti-apoptotic and cisplatin uptake-blocking properties. The broadest range of protection was achieved when the experimental flow used preconditioning with an otoprotective compound and later a co-incubation with cisplatin. Protection against a high concentration of cisplatin was observed only in protocols using short exposure times (4 and 6 h). Conclusions: The data extracted from the selected papers confirm that despite the differences between the human and the zebra fish hearing thresholds (as affected by cisplatin), the sensory cells of zebrafish and larval zebrafish are a valuable tool which could be used: (i) for the discovery of novel otoprotective substances and compounds; (ii) to screen their side effects and (iii) to extend the knowledge on the mechanisms of cisplatin-induced inner ear damage. For future studies, the development of a consensus experimental protocol is highly recommended.

Pituitary adenylate cyclase-activating polypeptide (PACAP-38) is a common neuropeptide exerting a wide spectrum of functions in many fields, including immunology. In the present study, 5-day post-fertilization (dpf) zebrafish larvae of three diverse genetic lines [transgenic lines Tg(MPX:GFP) with GFP-labelled neutrophils and Tg(pou4f3:GAP-GFP) with GFP-labelled hair cells and the wild-type Tuebingen] were used to investigate an inhibitory role of PACAP-38 in inflammation associated with damaged hair cells of the lateral line. Individuals of each genetic line were assigned to four groups: (1) control, and those consisting of larvae exposed to (2) 10 µM CuSO4, (3) 10 µM CuSO4+100 nM PACAP-38 and (4) 100 nM PACAP-38, respectively. Forty-minute exposure to CuSO4 solution was applied to evoke necrosis of hair cells and consequent inflammation. The inhibitory role of PACAP-38 was investigated in vivo under a confocal microscope by counting neutrophils migrating towards damaged hair cells in Tg(MPX:GFP) larvae. In CuSO4-treated individuals, the number of neutrophils associated with hair cells was dramatically increased, while PACAP-38 co-treatment resulted in its over 2-fold decrease. However, co-treatment with PACAP-38 did not prevent hair cells from extensive necrosis, which was found in Tg(pou4f3:GAP-GFP) individuals. Real-Time PCR analysis performed in wild-type larvae demonstrated differential expression pattern of stress and inflammation inducible markers. The most significant findings showed that CuSO4 exposure up-regulated the expression of IL-8, IL-1β, IL-6 and ATF3, while after PACAP-38 co-treatment expression levels of these genes were significantly decreased. The presence of transcripts for all PACAP receptors in neutrophils was also revealed. Adcyap1r1a and vipr1b appeared to be predominant forms. The present results suggest that PACAP-38 should be considered as a factor playing an important regulatory role in inflammatory response associated with pathological processes affecting zebrafish hair cells and it cannot be excluded that this interesting property has more universal significance.