RESUMEN
The resurfacing of cutaneous wounds in mammals takes up to several weeks, but in zebrafish complete coverage is achieved within hours. New work uncovers that the rapid wound healing on zebrafish body surfaces involves the mobilization of fin-resident epithelial cells.
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Cicatrización de Heridas , Pez Cebra , Animales , Pez Cebra/fisiología , Cicatrización de Heridas/fisiología , Células Epiteliales/fisiología , Aletas de Animales/fisiología , PielRESUMEN
Micro-sensors, such as pressure and flow sensors, are usually adopted to attain actual fluid information around swimming biomimetic robotic fish for hydrodynamic analysis and control. However, most of the reported micro-sensors are mounted discretely on body surfaces of robotic fish and it is impossible to analyzed the hydrodynamics between the caudal fin and the fluid. In this work, a biomimetic caudal fin integrated with a resistive pressure sensor is designed and fabricated by laser machined conductive carbon fibre composites. To analyze the pressure exerted on the caudal fin during underwater oscillation, the pressure on the caudal fin is measured under different oscillating frequencies and angles. Then a model developed from Bernoulli equation indicates that the maximum pressure difference is linear to the quadratic power of the oscillating frequency and the maximum oscillating angle. The fluid disturbance generated by caudal fin oscillating increases with an increase of oscillating frequency, resulting in the decrease of the efficiency of converting the kinetic energy of the caudal fin oscillation into the pressure difference on both sides of the caudal fin. However, perhaps due to the longer stability time of the disturbed fluid, this conversion efficiency increases with the increase of the maximum oscillating angle. Additionally, the pressure variation of the caudal fin oscillating with continuous different oscillating angles is also demonstrated to be detected effectively. It is suggested that the caudal fin integrated with the pressure sensor could be used for sensing thein situflow field in real time and analyzing the hydrodynamics of biomimetic robotic fish.
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Aletas de Animales , Biomimética , Diseño de Equipo , Peces , Robótica , Natación , Animales , Robótica/instrumentación , Aletas de Animales/fisiología , Biomimética/instrumentación , Biomimética/métodos , Peces/fisiología , Natación/fisiología , Hidrodinámica , Análisis de Falla de Equipo , Transductores de Presión , Presión , Materiales Biomiméticos , TransductoresRESUMEN
Regenerative potential is governed by a complex process of transcriptional reprogramming, involving chromatin reorganization and dynamics in transcription factor binding patterns throughout the genome. The degree to which chromatin and epigenetic changes contribute to this process remains only partially understood. Here we provide a modified CUT&Tag protocol suitable for improved characterization and interrogation of changes in chromatin modifications during adult fin regeneration in zebrafish. Our protocol generates data that recapitulates results from previously published ChIP-Seq methods, requires far fewer cells as input, and significantly improves signal to noise ratios. We deliver high-resolution enrichment maps for H3K4me3 of uninjured and regenerating fin tissues. During regeneration, we find that H3K4me3 levels increase over gene promoters which become transcriptionally active and genes which lose H3K4me3 become silenced. Interestingly, these reprogramming events recapitulate the H3K4me3 patterns observed in developing fin folds of 24-h old zebrafish embryos. Our results indicate that changes in genomic H3K4me3 patterns during fin regeneration occur in a manner consistent with reactivation of developmental programs, demonstrating CUT&Tag to be an effective tool for profiling chromatin landscapes in regenerating tissues.
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Aletas de Animales , Histonas , Regeneración , Pez Cebra , Animales , Histonas/metabolismo , Histonas/genética , Aletas de Animales/metabolismo , Aletas de Animales/fisiología , Cromatina/metabolismoRESUMEN
Regenerating tissues must remember or interpret their spatial position, using this information to restore original size and patterning. The external skeleton of the zebrafish caudal fin is composed of 18 rays; after any portion of the fin is amputated, position-dependent regenerative growth restores each ray to its original length. We tested for transcriptional differences during regeneration of proximal versus distal tissues and identified 489 genes that differed in proximodistal expression. Thyroid hormone directs multiple aspects of ray patterning along the proximodistal axis, and we identified 364 transcripts showing a proximodistal expression pattern that was dependent on thyroid hormone context. To test what aspects of ray positional identity are directed by extrinsic environental cues versus remembered identity autonomous to the tissue, we transplanted distal portions of rays to proximal environments and evaluated regeneration within the new location. Native regenerating proximal tissue showed robust expression of scpp7, a transcript with thyroid-regulated proximal enrichment; in contrast, regenerating rays originating from transplanted distal tissue showed reduced (distal-like) expression during outgrowth. These distal-to-proximal transplants regenerated far beyond the length of the graft itself, indicating that cues from the proximal environment promoted additional growth. Nonetheless, these transplants initiated regeneration at a much slower rate compared to controls, suggesting memory of distal identity was retained by the transplanted tissue. This early growth retardation caused rays that originated from transplants to grow noticeably shorter than neighboring native rays. While several aspects of fin ray morphology (bifurcation, segment length) were found to be determined by the environment, we found that both regeneration speed and ray length are remembered autonomously by tissues, and that persist through multiple rounds of amputation and regeneration.
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Aletas de Animales , Regeneración , Proteínas de Pez Cebra , Pez Cebra , Animales , Aletas de Animales/fisiología , Regeneración/fisiología , Proteínas de Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética , Tipificación del Cuerpo/genética , Tipificación del Cuerpo/fisiología , Hormonas Tiroideas/metabolismo , Regulación del Desarrollo de la Expresión Génica , Transducción de Señal/fisiologíaRESUMEN
Adult zebrafish are able to heal large-sized cutaneous wounds in hours with little to no scarring. This rapid re-epithelialization is crucial for preventing infection and jumpstarting the subsequent regeneration of damaged tissues. Despite significant progress in understanding this process, it remains unclear how vast numbers of epithelial cells are orchestrated on an organismic scale to ensure the timely closure of millimeter-sized wounds. Here, we report an unexpected role of adult zebrafish appendages (fins) in accelerating the re-epithelialization process. Through whole-body monitoring of single-cell dynamics in live animals, we found that fin-resident epithelial cells (FECs) are highly mobile and migrate to cover wounds in nearby body regions. Upon injury, FECs readily undergo organ-level mobilization, allowing for coverage of body surfaces of up to 4.78 mm2 in less than 8 h. Intriguingly, long-term fate-tracking experiments revealed that the migratory FECs are not short-lived at the wound site; instead, the cells can persist on the body surface for more than a year. Our experiments on "fin-less" and "fin-gaining" individuals demonstrated that the fin structures are not only capable of promoting rapid re-epithelialization but are also necessary for the process. We further found that fin-enriched extracellular matrix laminins promote the active migration of FECs by facilitating lamellipodia formation. These findings lead us to conclude that appendage structures in regenerative vertebrates, such as fins, may possess a previously unrecognized function beyond serving as locomotor organs. The appendages may also act as a massive reservoir of healing cells, which speed up wound closure and tissue repair.
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Células Epiteliales , Cicatrización de Heridas , Pez Cebra , Animales , Pez Cebra/fisiología , Células Epiteliales/fisiología , Cicatrización de Heridas/fisiología , Repitelización/fisiología , Movimiento Celular , Aletas de Animales/fisiología , Aletas de Animales/lesionesRESUMEN
We derive an equation that applies for the wing-beat frequency of flying animals and to the fin-stroke frequency of diving animals like penguins and whales. The equation states that the wing/fin-beat frequency is proportional to the square root of the animal's mass divided by the wing area. Data for birds, insects, bats, and even a robotic bird-supplemented by data for whales and penguins that must swim to stay submerged-show that the constant of proportionality is to a good approximation the same across all species; thus the equation is universal. The wing/fin-beat frequency equation is derived by dimensional analysis, which is a standard method of reasoning in physics. We finally demonstrate that a mathematically even simpler expression without the animal mass does not apply.
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Vuelo Animal , Alas de Animales , Animales , Alas de Animales/fisiología , Alas de Animales/anatomía & histología , Vuelo Animal/fisiología , Aletas de Animales/fisiología , Quirópteros/fisiología , Ballenas/fisiología , Spheniscidae/fisiología , Aves/fisiología , Modelos Biológicos , Natación/fisiología , Insectos/fisiologíaRESUMEN
Fish fins are remarkable devices of propulsion. Fin morphology is intimately linked to locomotor performance, and hence to behaviours that influence fitness, such as foraging and predator avoidance. This foreshadows a connection between fin morphology and variation in predation risk. Yet, whether prey can adjust fin morphology according to changes in perceived risk within their lifetime (a.k.a. predator-induced plasticity) remains elusive. Here, we quantify the structural size of five focal fins in crucian carp (Carassius carassius) following controlled manipulations to perceived predation risk (presence/absence of pike Esox lucius). We also assess if crucian carp respond to increased predation risk by shifts in dorsal fin colouration, and test for differences in how fish actively use their dorsal fins by quantifying the area of the fin displayed in behavioural trials. We find that crucian carp show phenotypic plasticity with regards to fin size as predator-exposed fish consistently have larger fins. Individuals exposed to perceived predation risk also increased dorsal fin darkness and actively displayed a larger area of the fin to potential predators. Our results thus provide compelling evidence for predator-induced fin enlargement, which should result in enhanced escape swimming performance. Moreover, fin-size plasticity may evolve synergistically with fin colouration and display behaviour, and we suggest that the adaptive value of this synergy is to enhance the silhouette of deep-bodied and hard-to-capture prey to deter gape-limited predators prior to attack. Together, our results provide new perspectives on the role of predation risk in development and evolution of fins.
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Aletas de Animales , Carpas , Esocidae , Conducta Predatoria , Animales , Aletas de Animales/fisiología , Aletas de Animales/anatomía & histología , Carpas/fisiología , Carpas/anatomía & histología , Esocidae/fisiología , Esocidae/anatomía & histología , Oscuridad , NataciónRESUMEN
INTRODUCTION: Non-healing wounds resulting from trauma, surgery, and chronic diseases annually affect millions of individuals globally, with limited therapeutic strategies available due to the incomplete understanding of the molecular processes governing tissue repair and regeneration. Salvianolic acid B (Sal B) has shown promising bioactivities in promoting angiogenesis and inhibiting inflammation. However, its regulatory mechanisms in tissue regeneration remain unclear. PURPOSE: This study aims to investigate the effects of Sal B on wound healing and regeneration processes, along with its underlying molecular mechanisms, by employing zebrafish as a model organism. METHODS: In this study, we employed a multifaceted approach to evaluate the impact of Sal B on zebrafish tail fin regeneration. We utilized whole-fish immunofluorescence, TUNEL staining, mitochondrial membrane potential (MMP), and Acridine Orange (AO) probes to analyze the tissue repair and regenerative under Sal B treatment. Additionally, we utilized transgenic zebrafish strains to investigate the migration of inflammatory cells during different phases of fin regeneration. To validate the importance of Caveolin-1 (Cav1) in tissue regeneration, we delved into its functional role using molecular docking and Morpholino-based gene knockdown techniques. Additionally, we quantified Cav1 expression levels through the application of in situ hybridization. RESULTS: Our findings demonstrated that Sal B expedites zebrafish tail fin regeneration through a multifaceted mechanism involving the promotion of cell proliferation, suppression of apoptosis, and enhancement of MMP. Furthermore, Sal B was found to exert regulatory control over the dynamic aggregation and subsequent regression of immune cells during tissue regenerative processes. Importantly, we observed that the knockdown of Cav1 significantly compromised tissue regeneration, leading to an excessive infiltration of immune cells and increased levels of apoptosis. Moreover, the knockdown of Cav1 also affects blastema formation, a critical process influenced by Cav1 in tissue regeneration. CONCLUSION: The results of this study showed that Sal B facilitated tissue repair and regeneration through regulating of immune cell migration and Cav1-mediated fibroblast activation, promoting blastema formation and development. This study highlighted the potential pharmacological effects of Sal B in promoting tissue regeneration. These findings contributed to the advancement of regenerative medicine research and the development of novel therapeutic approaches for trauma.
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Benzofuranos , Caveolina 1 , Cicatrización de Heridas , Pez Cebra , Animales , Aletas de Animales/efectos de los fármacos , Aletas de Animales/fisiología , Animales Modificados Genéticamente , Apoptosis/efectos de los fármacos , Benzofuranos/farmacología , Caveolina 1/metabolismo , Movimiento Celular/efectos de los fármacos , Depsidos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Simulación del Acoplamiento Molecular , Regeneración/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Proteínas de Pez Cebra/metabolismoRESUMEN
BACKGROUND: The larval zebrafish tail fin can completely regenerate in 3 days post amputation. mTOR, the main regulator of cell growth and metabolism, plays an essential role in regeneration. Lots of studies have documented the role of mTOR in regeneration. However, the mechanisms involved are still not fully elucidated. MATERIALS AND RESULTS: This study aimed to explore the role and mechanism of mTOR in the regeneration of larval zebrafish tail fins. Initially, the spatial and temporal expression of mTOR signaling in the larval fin was examined, revealing its activation following tail fin amputation. Subsequently, a mTOR knockout (mTOR-KO) zebrafish line was created using CRISPR/Cas9 gene editing technology. The investigation demonstrated that mTOR depletion diminished the proliferative capacity of epithelial and mesenchymal cells during fin regeneration, with no discernible impact on cell apoptosis. Insight from SMART-seq analysis uncovered alterations in the cell cycle, mitochondrial functions and metabolic pathways when mTOR signaling was suppressed during fin regeneration. Furthermore, mTOR was confirmed to enhance mitochondrial functions and Ca2 + activation following fin amputation. These findings suggest a potential role for mTOR in promoting mitochondrial fission to facilitate tail fin regeneration. CONCLUSION: In summary, our results demonstrated that mTOR played a key role in larval zebrafish tail fin regeneration, via promoting mitochondrial fission and proliferation of blastema cells.
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Aletas de Animales , Proliferación Celular , Larva , Mitocondrias , Regeneración , Serina-Treonina Quinasas TOR , Cola (estructura animal) , Proteínas de Pez Cebra , Pez Cebra , Animales , Pez Cebra/genética , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Regeneración/genética , Regeneración/fisiología , Proliferación Celular/genética , Aletas de Animales/fisiología , Proteínas de Pez Cebra/genética , Cola (estructura animal)/fisiología , Larva/genética , Mitocondrias/genética , Mitocondrias/metabolismo , Mutación , Transducción de Señal/genética , Dinámicas Mitocondriales/genética , Dinámicas Mitocondriales/fisiologíaRESUMEN
HEADINGS ETHNOPHARMACOLOGICAL RELEVANCE: Rehmanniae Radix Praeparata (RRP), a staple in traditional Chinese medicine, is derived from Rehmannia glutinosa Libosch and is renowned for its wound-healing properties. Despite its clinical prevalence, the molecular mechanisms underlying RRP's wound-healing effects have not been fully elucidated. AIM OF THE STUDY: This research endeavored to delineate the molecular and cellular mechanisms underlying the beneficial effects of RRP on wound healing, utilizing a zebrafish model. MATERIALS AND METHODS: Zebrafish larvae at 3 days post-fertilization were amputated at the fin and subsequently treated with RRP. The pro-wound healing and regenerative effects of RRP were evaluated through morphological analysis, assessment of cell proliferation and apoptosis, Additionally, mechanistic insights were gained through a comprehensive approach encompassing network pharmacology analysis, cell tracing, RNA-sequencing, CRISPR/Cas9 gene editing, and pharmacological inhibition. RESULTS: Our findings demonstrate that RRP significantly accelerates caudal fin regeneration in zebrafish following injury by suppressing cell apoptosis, promoting cell proliferation, and upregulating the expression of regenerative-related genes. Furthermore, RRP triggers autophagy signals during the regenerative process, which is attenuated by the autophagy inhibitor chloroquine (CQ). Notably, the administration of RRP enhances the expression of ahr1 and ahr2 in the regenerating fin. Genetic knockout of ahr1a, ahr1b, or ahr2 using CRISPR/Cas9, or pharmacological blockade of AHR signals with the antagonist CH-223191, diminishes the regenerative potential of RRP. Remarkably, zebrafish lacking ahr2 completely lose their fin regeneration ability. Additionally, inhibition of AHR signaling suppresses autophagy signaling during fin regeneration. CONCLUSIONS: This study uncovers that RRP stimulates fin regeneration in zebrafish by inducing AHR signals and, at least partially, activating the autophagy process. These findings provide novel insights into the molecular mechanisms underlying the wound-healing effects of RRP and may pave the way for the development of novel therapeutic strategies.
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Aletas de Animales , Autofagia , Proliferación Celular , Receptores de Hidrocarburo de Aril , Regeneración , Rehmannia , Pez Cebra , Animales , Autofagia/efectos de los fármacos , Aletas de Animales/efectos de los fármacos , Aletas de Animales/fisiología , Receptores de Hidrocarburo de Aril/metabolismo , Receptores de Hidrocarburo de Aril/genética , Rehmannia/química , Regeneración/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Apoptosis/efectos de los fármacos , Extractos Vegetales/farmacología , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Raíces de PlantasRESUMEN
State-of-the-art morphing materials are either very compliant to achieve large shape changes (flexible metamaterials, compliant mechanisms, hydrogels), or very stiff but with infinitesimal changes in shape that require large actuation forces (metallic or composite panels with piezoelectric actuation). Morphing efficiency and structural stiffness are therefore mutually exclusive properties in current engineering morphing materials, which limits the range of their applicability. Interestingly, natural fish fins do not contain muscles, yet they can morph to large amplitudes with minimal muscular actuation forces from the base while producing large hydrodynamic forces without collapsing. This sophisticated mechanical response has already inspired several synthetic fin rays with various applications. However, most 'synthetic' fin rays have only considered uniform properties and structures along the rays while in natural fin rays, gradients of properties are prominent. In this study, we designed, modeled, fabricated and tested synthetic fin rays with bioinspired gradients of properties. The rays were composed of two hemitrichs made of a stiff polymer, joined by a much softer core region made of elastomeric ligaments. Using combinations of experiments and nonlinear mechanical models, we found that gradients in both the core region and hemitrichs can increase the morphing and stiffening response of individual rays. Introducing a positive gradient of ligament density in the core region (the density of ligament increases towards the tip of the ray) decreased the actuation force required for morphing and increased overall flexural stiffness. Introducing a gradient of property in the hemitrichs, by tapering them, produced morphing deformations that were distributed over long distances along the length of the ray. These new insights on the interplay between material architecture and properties in nonlinear regimes of deformation can improve the designs of morphing structures that combine high morphing efficiency and high stiffness from external forces, with potential applications in aerospace or robotics.
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Aletas de Animales , Materiales Biomiméticos , Animales , Aletas de Animales/fisiología , Aletas de Animales/anatomía & histología , Fenómenos Biomecánicos , Biomimética/métodos , Peces/fisiología , Peces/anatomía & histologíaRESUMEN
Animals have evolved highly effective locomotion capabilities in terrestrial, aerial, and aquatic environments. Over life's history, mass extinctions have wiped out unique animal species with specialized adaptations, leaving paleontologists to reconstruct their locomotion through fossil analysis. Despite advancements, little is known about how extinct megafauna, such as the Ichthyosauria one of the most successful lineages of marine reptiles, utilized their varied morphologies for swimming. Traditional robotics struggle to mimic extinct locomotion effectively, but the emerging soft robotics field offers a promising alternative to overcome this challenge. This paper aims to bridge this gap by studyingMixosauruslocomotion with soft robotics, combining material modeling and biomechanics in physical experimental validation. Combining a soft body with soft pneumatic actuators, the soft robotic platform described in this study investigates the correlation between asymmetrical fins and buoyancy by recreating the pitch torque generated by extinct swimming animals. We performed a comparative analysis of thrust and torque generated byCarthorhyncus,Utatsusaurus,Mixosaurus,Guizhouichthyosaurus, andOphthalmosaurustail fins in a flow tank. Experimental results suggest that the pitch torque on the torso generated by hypocercal fin shapes such as found in model systems ofGuizhouichthyosaurus,MixosaurusandUtatsusaurusproduce distinct ventral body pitch effects able to mitigate the animal's non-neutral buoyancy. This body pitch control effect is particularly pronounced inGuizhouichthyosaurus, which results suggest would have been able to generate high ventral pitch torque on the torso to compensate for its positive buoyancy. By contrast, homocercal fin shapes may not have been conducive for such buoyancy compensation, leaving torso pitch control to pectoral fins, for example. Across the range of the actuation frequencies of the caudal fins tested, resulted in oscillatory modes arising, which in turn can affect the for-aft thrust generated.
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Aletas de Animales , Modelos Biológicos , Robótica , Natación , Animales , Natación/fisiología , Aletas de Animales/fisiología , Aletas de Animales/anatomía & histología , Robótica/instrumentación , Fenómenos Biomecánicos , Reptiles/fisiología , Reptiles/anatomía & histología , Fósiles , Simulación por Computador , Biomimética/métodosRESUMEN
Rising in popularity as a model organism in the classroom, zebrafish have numerous characteristics that make them ideal for teaching. In this study, we describe an experiment that helps students better understand the concept of tissue regeneration and the genes that control it. This experiment utilizes a dominant negative transgene for fgfr1 and allows students to observe the consequences of its activation. The first part of the laboratory is hands-on, and includes details of the amputation of caudal fins, heat shocking, general fish care, and visual observations. Over the course of a week, students observed the differences between the activated and unactivated transgene in the zebrafish. The second part was literature based, in which students tried to determine which gene is responsible for inhibiting regeneration. This encouraged students to sharpen their skills of deductive reasoning and critical thinking as they conduct research based on the information they receive about dominant negative receptors and transgenes. Having both a hands-on and critical thinking component in the laboratory helped synthesize the learning goals and allowed students to actively participate.
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Proteínas de Pez Cebra , Pez Cebra , Animales , Pez Cebra/fisiología , Proteínas de Pez Cebra/genética , Cola (estructura animal)/fisiología , Aletas de Animales/fisiologíaRESUMEN
Vascular mimicry has been thoroughly investigated in tumor angiogenesis. In this study, we demonstrate for the first time that a process closely resembling tumor vascular mimicry is present during physiological blood vessel formation in tissue regeneration using the zebrafish fin regeneration assay. At the fin-regenerating front, vasculature is formed by mosaic blood vessels with endothelial-like cells possessing the morphological phenotype of a macrophage and co-expressing both endothelial and macrophage markers within single cells. Our data demonstrate that the vascular segments of the regenerating tissue expand, in part, through the transformation of adjacent macrophages into endothelial-like cells, forming functional, perfused channels and contributing to the de novo formation of microvasculature. Inhibiting the formation of tubular vascular-like structures by CVM-1118 prevents vascular mimicry and network formation resulting in a 70% shorter regeneration area with 60% reduced vessel growth and a complete absence of any signs of regeneration in half of the fin area. Additionally, this is associated with a significant reduction in macrophages. Furthermore, depleting macrophages using macrophage inhibitor PLX-3397, results in impaired tissue regeneration and blood vessel formation, namely a reduction in the regeneration area and vessel network by 75% in comparison to controls.
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Aletas de Animales , Macrófagos , Neovascularización Fisiológica , Regeneración , Pez Cebra , Animales , Macrófagos/metabolismo , Aletas de Animales/fisiología , Aletas de Animales/irrigación sanguínea , Vasos Sanguíneos/fisiología , Células Endoteliales/metabolismoRESUMEN
In this study, we comprehensively searched for fish-specific genes in gnathostomes that contribute to development of the fin, a fish-specific trait. Many previous reports suggested that animal group-specific genes are often important for group-specific traits. Clarifying the roles of fish-specific genes in fin development of gnathostomes, for example, can help elucidate the mechanisms underlying the formation of this trait. We first identified 91 fish-specific genes in gnathostomes by comparing the gene repertoire in 16 fish and 35 tetrapod species. RNA-seq analysis narrowed down the 91 candidates to 33 genes that were expressed in the developing pectoral fin. We analyzed the functions of approximately half of the candidate genes by loss-of-function analysis in zebrafish. We found that some of the fish-specific and fin development-related genes, including fgf24 and and1/and2, play roles in fin development. In particular, the newly identified fish-specific gene qkia is expressed in the developing fin muscle and contributes to muscle morphogenesis in the pectoral fin as well as body trunk. These results indicate that the strategy of identifying animal group-specific genes is functional and useful. The methods applied here could be used in future studies to identify trait-associated genes in other animal groups.
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Proteínas de Pez Cebra , Pez Cebra , Animales , Pez Cebra/genética , Proteínas de Pez Cebra/genética , Genómica , Aletas de Animales/fisiologíaRESUMEN
OBJECTIVES: Bone tissue in bony fish demonstrates a remarkable ability to regenerate, particularly evident following induction of extensive bone defects, such as fin amputation. This regenerative capacity has been reported to be promoted by the immunosuppressant FK506, yet its precise effects on bone cells during fin regeneration remains insufficiently elucidated. This study aims to investigate the effects of FK506 treatment on bone morphology, osteoblasts, and osteoclasts in the bony fin rays of osterix promoter-DsRed/TRAP promoter-EGFP double transgenic (Tg) medaka. METHODS: The caudal fin of double Tg medaka was amputated, followed by a 20-day treatment with FK506 (1.0 µg/ml) to observe its effects on fin regeneration. Additionally, the regenerated caudal fin area underwent evaluation using genetic analysis and cell proliferation assays. RESULTS: FK506 treatment significantly increased osterix-positive osteoblast formation, resulting in both a significantly longer fin length and fewer joints in the bony fin rays formed during fin regeneration. Notably, TRAP-positive osteoclast formation and bone resorption were observed to occur primarily during the latter stages of fin regeneration. Furthermore, while the expression levels of osteoblast-related genes in the regenerated area remained unchanged following FK506 treatment, a heightened cell proliferation was observed at the tip of the fin. CONCLUSIONS: Our findings suggest that treatment with FK506 promotes bone regeneration by increasing the number of osteoblasts in the amputated area of the fin. However, long-term treatment disrupts regular bone metabolism by inducing abnormal osteoclast formation.
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Aletas de Animales , Animales Modificados Genéticamente , Regeneración Ósea , Oryzias , Tacrolimus , Animales , Tacrolimus/farmacología , Oryzias/genética , Aletas de Animales/efectos de los fármacos , Aletas de Animales/fisiología , Regeneración Ósea/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Proliferación Celular/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Inmunosupresores/farmacologíaRESUMEN
Fins from ray-finned fishes do not contain muscles, yet fish can change the shape of their fins with high precision and speed, while producing large hydrodynamic forces without collapsing. This remarkable performance has been intriguing researchers for decades, but experiments have so far focused on homogenized properties, and models were developed only for small deformations and small rotations. Here we present fully instrumented micromechanical tests on individual rays from Rainbow trout in both morphing and flexural deflection mode and at large deflections. We then present a nonlinear mechanical model of the ray that captures the key structural elements controlling the mechanical behavior of rays under large deformations, which we successfully fit onto the experiments for property identification. We found that the flexural stiffness of the mineralized layers in the rays (hemitrichs) is 5-6 times lower than their axial stiffness, an advantageous combination to produce stiff morphing. In addition, the collagenous core region can be modeled with spring elements which are 3-4 orders of magnitude more compliant than the hemitrichs. This fibrillar structure provides negligible resistance to shearing from the initial position, but it prevents buckling and collapse of the structure at large deformations. These insights from the experiments and nonlinear models can serve as new guidelines for the design of efficient bioinspired stiff morphing materials and structures at large deformations. STATEMENT OF SIGNIFICANCE: Fins from ray-finned fishes do not contain muscles, yet fish can change the shape of their fins with high precision and speed, while producing large hydrodynamic forces without collapsing. Experiments have so far focused on homogenized properties, and models were developed only for small deformations and small rotations providing limited insight into the rich nonlinear mechanics of natural rays. We present micromechanical tests in both morphing and flexural deflection mode on individual rays, a nonlinear model of the ray that captures the mechanical behavior of rays under large deformations and combine microCT measurements to generate new insights into the nonlinear mechanics of rays. These insights can serve as new guidelines for the design of efficient bioinspired stiff morphing materials and structures at large deformations.
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Peces , Natación , Animales , Fenómenos Biomecánicos , Natación/fisiología , Dinámicas no Lineales , Microtomografía por Rayos X , Aletas de Animales/fisiologíaRESUMEN
Processes that regulate size and patterning along an axis must be highly integrated to generate robust shapes; relative changes in these processes underlie both congenital disease and evolutionary change. Fin length mutants in zebrafish have provided considerable insight into the pathways regulating fin size, yet signals underlying patterning have remained less clear. The bony rays of the fins possess distinct patterning along the proximodistal axis, reflected in the location of ray bifurcations and the lengths of ray segments, which show progressive shortening along the axis. Here, we show that thyroid hormone (TH) regulates aspects of proximodistal patterning of the caudal fin rays, regardless of fin size. TH promotes distal gene expression patterns, coordinating ray bifurcations and segment shortening with skeletal outgrowth along the proximodistal axis. This distalizing role for TH is conserved between development and regeneration, in all fins (paired and medial), and between Danio species as well as distantly related medaka. During regenerative outgrowth, TH acutely induces Shh-mediated skeletal bifurcation. Zebrafish have multiple nuclear TH receptors, and we found that unliganded Thrab-but not Thraa or Thrb-inhibits the formation of distal features. Broadly, these results demonstrate that proximodistal morphology is regulated independently from size-instructive signals. Modulating proximodistal patterning relative to size-either through changes to TH metabolism or other hormone-independent pathways-can shift skeletal patterning in ways that recapitulate aspects of fin ray diversity found in nature.
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Proteínas de Pez Cebra , Pez Cebra , Animales , Pez Cebra/fisiología , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Hormonas Tiroideas/genética , Aletas de Animales/fisiología , Regeneración/fisiologíaRESUMEN
The remarkable ability of some marine animals to identify flow structures and parameters using complex non-visual sensors, such as lateral lines of fish and the whiskers of seals, has been an area of investigation for researchers looking to apply this ability to artificial robotic swimmers, which could lead to improvements in autonomous navigation and efficiency. Several species of fish in particular have been known to school effectively, even when blind. Beyond specialized sensors like the lateral lines, it is now known that some fish use purely proprioceptive sensing, using the kinematics of their fins or tails to sense their surroundings. In this paper we show that the kinematics of a body with a passive tail encode information about the ambient flow, which can be deciphered through machine learning. We demonstrate this with experimental data of the angular velocity of a hydrofoil with a passive tail that lies in the wake generated by an upstream oscillating body. Using convolutional neural networks, we show that with the kinematic data from the downstream body with a tail, the wakes can be better classified than in the case of a body without a tail. This superior sensing ability exists for a body with a tail, even if only the kinematics of the main body are used as input for the machine learning. This shows that beyond generating 'additional inputs', passive tails modulate the response of the main body in manner that is useful for hydrodynamic sensing. These findings have clear application for improving the sensing abilities of bioinspired swimming robots.
Asunto(s)
Peces , Natación , Animales , Peces/fisiología , Fenómenos Biomecánicos , Natación/fisiología , Hidrodinámica , Aletas de Animales/fisiología , Cola (estructura animal)/fisiologíaRESUMEN
Nearly all fish have flexible bodies that bend as a result of internal muscular forces and external fluid forces that are dynamically coupled with the mechanical properties of the body. Swimming is therefore strongly influenced by the body's flexibility, yet we do not know how fish species vary in their flexibility and in their ability to modulate flexibility with muscle activity. A more fundamental problem is our lack of knowledge about how any of these differences in flexibility translate into swimming performance. Thus, flexibility represents a hidden axis of diversity among fishes that may have substantial impacts on swimming performance. Although engineers have made substantial progress in understanding these fluid-structure interactions using physical and computational models, the last biological review of these interactions and how they give rise to fish swimming was carried out more than 20 years ago. In this Review, we summarize work on passive and active body mechanics in fish, physical models of fish and bioinspired robots. We also revisit some of the first studies to explore flexural stiffness and discuss their relevance in the context of more recent work. Finally, we pose questions and suggest future directions that may help reveal important links between flexibility and swimming performance.