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1.
Sensors (Basel) ; 24(15)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39123885

RESUMEN

Pattern recognition (PR)-based myoelectric control systems can naturally provide multifunctional and intuitive control of upper limb prostheses and restore lost limb function, but understanding their robustness remains an open scientific question. This study investigates how limb positions and electrode shifts-two factors that have been suggested to cause classification deterioration-affect classifiers' performance by quantifying changes in the class distribution using each factor as a class and computing the repeatability and modified separability indices. Ten intact-limb participants took part in the study. Linear discriminant analysis (LDA) was used as the classifier. The results confirmed previous studies that limb positions and electrode shifts deteriorate classification performance (14-21% decrease) with no difference between factors (p > 0.05). When considering limb positions and electrode shifts as classes, we could classify them with an accuracy of 96.13 ± 1.44% and 65.40 ± 8.23% for single and all motions, respectively. Testing on five amputees corroborated the above findings. We have demonstrated that each factor introduces changes in the feature space that are statistically new class instances. Thus, the feature space contains two statistically classifiable clusters when the same motion is collected in two different limb positions or electrode shifts. Our results are a step forward in understanding PR schemes' challenges for myoelectric control of prostheses and further validation needs be conducted on more amputee-related datasets.


Asunto(s)
Amputados , Miembros Artificiales , Electrodos , Electromiografía , Reconocimiento de Normas Patrones Automatizadas , Humanos , Electromiografía/métodos , Masculino , Adulto , Reconocimiento de Normas Patrones Automatizadas/métodos , Amputados/rehabilitación , Femenino , Análisis Discriminante , Adulto Joven , Extremidades/fisiología
2.
Nat Ecol Evol ; 8(8): 1505-1521, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39030276

RESUMEN

Species within nearly all extant animal lineages are capable of regenerating body parts. However, it remains unclear whether the gene expression programme controlling regeneration is evolutionarily conserved. Brittle stars are a species-rich class of echinoderms with outstanding regenerative abilities, but investigations into the genetic bases of regeneration in this group have been hindered by the limited genomic resources. Here we report a chromosome-scale genome assembly for the brittle star Amphiura filiformis. We show that the brittle star genome is the most rearranged among echinoderms sequenced so far, featuring a reorganized Hox cluster reminiscent of the rearrangements observed in sea urchins. In addition, we performed an extensive profiling of gene expression during brittle star adult arm regeneration and identified sequential waves of gene expression governing wound healing, proliferation and differentiation. We conducted comparative transcriptomic analyses with other invertebrate and vertebrate models for appendage regeneration and uncovered hundreds of genes with conserved expression dynamics, particularly during the proliferative phase of regeneration. Our findings emphasize the crucial importance of echinoderms to detect long-range expression conservation between vertebrates and classical invertebrate regeneration model systems.


Asunto(s)
Equinodermos , Genoma , Regeneración , Animales , Regeneración/genética , Equinodermos/genética , Equinodermos/fisiología , Extremidades/fisiología , Transcriptoma
3.
J Hum Evol ; 194: 103567, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39068699

RESUMEN

Hominoids exhibit a strikingly diverse set of locomotor adaptations-including knuckle-walking, brachiation, quadrumanuous suspension, and striding bipedalism-while also possessing morphologies associated with forelimb suspension. It has been suggested that changes in limb element integration facilitated the evolution of diverse locomotor modes by reducing covariation between serial homologs and allowing the evolution of a greater diversity of limb lengths. Here, I compare limb element integration in hominoids with that of other primate taxa, including two that have converged with them in forelimb morphology, Ateles and Pygathrix. Ateles is part of a clade that, such as hominoids, exhibits diverse locomotor adaptations, whereas Pygathrix is an anomaly in a much more homogeneous (in terms of locomotor adaptations) clade. I find that all atelines (and possibly all atelids), not just Ateles, share reduced limb element integration with hominoids. Pygathrix does not, however, instead resembling other members of its own family. Indriids also seem to have higher limb integration than apes, despite using their forelimbs and hindlimbs in divergent ways, although there is more uncertainty in this group due to poor sample size. These results suggest that reduced limb integration is characteristic of certain taxonomic groups with high locomotor diversity rather than taxa with specific, specialized locomotor adaptations. This is consistent with the hypothesis that reduced integration serves to open new areas of morphospace to those clades while suggesting that derived locomotion with divergent demands on limbs is not necessarily associated with reduced limb integration.


Asunto(s)
Locomoción , Animales , Evolución Biológica , Adaptación Fisiológica , Fósiles/anatomía & histología , Primates/fisiología , Primates/anatomía & histología , Extremidades/anatomía & histología , Extremidades/fisiología , Miembro Anterior/anatomía & histología , Miembro Anterior/fisiología
4.
Dev Biol ; 515: 151-159, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39067503

RESUMEN

Many salamanders can completely regenerate a fully functional limb. Limb regeneration is a carefully coordinated process involving several defined stages. One key event during the regeneration process is the patterning of the blastema to inform cells of what they must differentiate into. Although it is known that many genes involved in the initial development of the limb are re-used during regeneration, the exact molecular circuitry involved in this process is not fully understood. Several large-scale transcriptional profiling studies of axolotl limb regeneration have identified many transcription factors that are up-regulated after limb amputation. Sall4 is a transcription factor that has been identified to play essential roles in maintaining cells in an undifferentiated state during development and also plays a unique role in limb development. Inactivation of Sall4 during limb bud development results in defects in anterior-posterior patterning of the limb. Sall4 has been found to be up-regulated during limb regeneration in both Xenopus and salamanders, but to date it function has been untested. We confirmed that Sall4 is up-regulated during limb regeneration in the axolotl using qRT-PCR and identified that it is present in the skin cells and also in cells within the blastema. Using CRISPR technology we microinjected gRNAs specific for Sall4 complexed with cas9 protein into the blastema to specifically knockout Sall4 in blastema cells only. This resulted in limb regenerate defects, including missing digits, fusion of digit elements, and defects in the radius and ulna. This suggests that during regeneration Sall4 may play a similar role in regulating the specification of anterior-proximal skeletal elements.


Asunto(s)
Ambystoma mexicanum , Tipificación del Cuerpo , Extremidades , Regeneración , Factores de Transcripción , Animales , Regeneración/genética , Regeneración/fisiología , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Extremidades/fisiología , Extremidades/embriología , Ambystoma mexicanum/genética , Ambystoma mexicanum/fisiología , Tipificación del Cuerpo/genética , Regulación del Desarrollo de la Expresión Génica/genética , Proteínas Anfibias/genética , Proteínas Anfibias/metabolismo
5.
PLoS Biol ; 22(7): e3002703, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38959259

RESUMEN

The unpredictable nature of our world can introduce a variety of errors in our actions, including sensory prediction errors (SPEs) and task performance errors (TPEs). SPEs arise when our existing internal models of limb-environment properties and interactions become miscalibrated due to changes in the environment, while TPEs occur when environmental perturbations hinder achievement of task goals. The precise mechanisms employed by the sensorimotor system to learn from such limb- and task-related errors and improve future performance are not comprehensively understood. To gain insight into these mechanisms, we performed a series of learning experiments wherein the location and size of a reach target were varied, the visual feedback of the motion was perturbed in different ways, and instructions were carefully manipulated. Our findings indicate that the mechanisms employed to compensate SPEs and TPEs are dissociable. Specifically, our results fail to support theories that suggest that TPEs trigger implicit refinement of reach plans or that their occurrence automatically modulates SPE-mediated learning. Rather, TPEs drive improved action selection, that is, the selection of verbally sensitive, volitional strategies that reduce future errors. Moreover, we find that exposure to SPEs is necessary and sufficient to trigger implicit recalibration. When SPE-mediated implicit learning and TPE-driven improved action selection combine, performance gains are larger. However, when actions are always successful and strategies are not employed, refinement in behavior is smaller. Flexibly weighting strategic action selection and implicit recalibration could thus be a way of controlling how much, and how quickly, we learn from errors.


Asunto(s)
Retroalimentación Sensorial , Aprendizaje , Desempeño Psicomotor , Humanos , Aprendizaje/fisiología , Masculino , Femenino , Desempeño Psicomotor/fisiología , Adulto , Adulto Joven , Retroalimentación Sensorial/fisiología , Análisis y Desempeño de Tareas , Extremidades/fisiología
6.
Development ; 151(20)2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39012059

RESUMEN

Regeneration is the remarkable phenomenon through which an organism can regrow lost or damaged parts with fully functional replacements, including complex anatomical structures, such as limbs. In 2019, Development launched its 'Model systems for regeneration' collection, a series of articles introducing some of the most popular model organisms for studying regeneration in vivo. To expand this topic further, this Perspective conveys the voices of five expert biologists from the field of regenerative biology, each of whom showcases some less well-known, but equally extraordinary, species for studying regeneration.


Asunto(s)
Regeneración , Animales , Humanos , Extremidades/fisiología , Modelos Biológicos , Regeneración/fisiología
7.
Curr Biol ; 34(14): R677-R679, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39043138

RESUMEN

Social insect workers, renowned for their altruism, are frequently perceived as 'disposable'. A new study finds that ants amputate the limbs of nestmates, which saves them from infection, and indicates that worker care is as critical to colony success as sacrifice.


Asunto(s)
Hormigas , Extremidades , Animales , Hormigas/fisiología , Extremidades/fisiología , Evolución Social , Conducta Social , Amputación Quirúrgica , Conducta Animal/fisiología
8.
Sensors (Basel) ; 24(13)2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-39001085

RESUMEN

Recently, posture recognition technology has advanced rapidly. Herein, we present a novel posture angle calculation system utilizing a single inertial measurement unit and a spatial geometric equation to accurately identify the three-dimensional (3D) motion angles and postures of both the upper and lower limbs of the human body. This wearable system facilitates continuous monitoring of body movements without the spatial limitations or occlusion issues associated with camera-based methods. This posture-recognition system has many benefits. Providing precise posture change information helps users assess the accuracy of their movements, prevent sports injuries, and enhance sports performance. This system employs a single inertial sensor, coupled with a filtering mechanism, to calculate the sensor's trajectory and coordinates in 3D space. Subsequently, the spatial geometry equation devised herein accurately computed the joint angles for changing body postures. To validate its effectiveness, the joint angles estimated from the proposed system were compared with those from dual inertial sensors and image recognition technology. The joint angle discrepancies for this system were within 10° and 5° when compared with dual inertial sensors and image recognition technology, respectively. Such reliability and accuracy of the proposed angle estimation system make it a valuable reference for assessing joint angles.


Asunto(s)
Postura , Humanos , Postura/fisiología , Dispositivos Electrónicos Vestibles , Fenómenos Biomecánicos/fisiología , Movimiento/fisiología , Masculino , Algoritmos , Extremidades/fisiología
9.
Bioinspir Biomim ; 19(5)2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39042109

RESUMEN

This paper broadly summarizes the variation of design features found in vertebrate limbs and analyses the resultant versatility and multifunctionality in order to make recommendations for bioinspired robotics. The vertebrate limb pattern (e.g. shoulder, elbow, wrist and digits) has been proven to be very successful in many different applications in the animal kingdom. However, the actual level of optimality of the limb for each animal application is not clear because for some cases (e.g. whale flippers and bird wings), the basic skeletal layout is assumed to be highly constrained by evolutionary ancestry. This paper addresses this important and fundamental question of optimality by analysing six limbs with contrasting functions: human arm, whale flipper, bird wing, human leg, feline hindlimb and frog hindlimb. A central finding of this study is that the vertebrate limb pattern is highly versatile and optimal not just for arms and legs but also for flippers and wings. One key design feature of the vertebrate limb pattern is that of networks of segmented bones that enable smooth morphing of shapes as well as multifunctioning structures. Another key design feature is that of linkage mechanisms that fine-tune motions and mechanical advantage. A total of 52 biomechanical design features of the vertebrate limb are identified and tabulated for these applications. These tables can be a helpful reference for designers of bioinspired robotic and prosthetic limbs. The vertebrate limb has significant potential for the bioinspired design of robotic and prosthetic limbs, especially because of progress in the development of soft actuators.


Asunto(s)
Biomimética , Extremidades , Robótica , Animales , Humanos , Robótica/métodos , Robótica/instrumentación , Biomimética/métodos , Extremidades/fisiología , Vertebrados/fisiología , Vertebrados/anatomía & histología , Miembros Artificiales , Fenómenos Biomecánicos , Modelos Biológicos
10.
Nature ; 631(8020): 360-368, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38926570

RESUMEN

A deep understanding of how the brain controls behaviour requires mapping neural circuits down to the muscles that they control. Here, we apply automated tools to segment neurons and identify synapses in an electron microscopy dataset of an adult female Drosophila melanogaster ventral nerve cord (VNC)1, which functions like the vertebrate spinal cord to sense and control the body. We find that the fly VNC contains roughly 45 million synapses and 14,600 neuronal cell bodies. To interpret the output of the connectome, we mapped the muscle targets of leg and wing motor neurons using genetic driver lines2 and X-ray holographic nanotomography3. With this motor neuron atlas, we identified neural circuits that coordinate leg and wing movements during take-off. We provide the reconstruction of VNC circuits, the motor neuron atlas and tools for programmatic and interactive access as resources to support experimental and theoretical studies of how the nervous system controls behaviour.


Asunto(s)
Conectoma , Drosophila melanogaster , Neuronas Motoras , Tejido Nervioso , Vías Nerviosas , Sinapsis , Animales , Femenino , Conjuntos de Datos como Asunto , Drosophila melanogaster/anatomía & histología , Drosophila melanogaster/citología , Drosophila melanogaster/fisiología , Drosophila melanogaster/ultraestructura , Extremidades/fisiología , Extremidades/inervación , Holografía , Microscopía Electrónica , Neuronas Motoras/citología , Neuronas Motoras/fisiología , Neuronas Motoras/ultraestructura , Movimiento , Músculos/inervación , Músculos/fisiología , Tejido Nervioso/anatomía & histología , Tejido Nervioso/citología , Tejido Nervioso/fisiología , Tejido Nervioso/ultraestructura , Vías Nerviosas/citología , Vías Nerviosas/fisiología , Vías Nerviosas/ultraestructura , Sinapsis/fisiología , Sinapsis/ultraestructura , Tomografía por Rayos X , Alas de Animales/inervación , Alas de Animales/fisiología
11.
Nature ; 631(8020): 369-377, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38926579

RESUMEN

Animal movement is controlled by motor neurons (MNs), which project out of the central nervous system to activate muscles1. MN activity is coordinated by complex premotor networks that facilitate the contribution of individual muscles to many different behaviours2-6. Here we use connectomics7 to analyse the wiring logic of premotor circuits controlling the Drosophila leg and wing. We find that both premotor networks cluster into modules that link MNs innervating muscles with related functions. Within most leg motor modules, the synaptic weights of each premotor neuron are proportional to the size of their target MNs, establishing a circuit basis for hierarchical MN recruitment. By contrast, wing premotor networks lack proportional synaptic connectivity, which may enable more flexible recruitment of wing steering muscles. Through comparison of the architecture of distinct motor control systems within the same animal, we identify common principles of premotor network organization and specializations that reflect the unique biomechanical constraints and evolutionary origins of leg and wing motor control.


Asunto(s)
Conectoma , Drosophila melanogaster , Extremidades , Neuronas Motoras , Vías Nerviosas , Sinapsis , Alas de Animales , Animales , Femenino , Masculino , Drosophila melanogaster/anatomía & histología , Drosophila melanogaster/citología , Drosophila melanogaster/fisiología , Extremidades/inervación , Extremidades/fisiología , Neuronas Motoras/fisiología , Movimiento/fisiología , Músculos/inervación , Músculos/fisiología , Red Nerviosa/anatomía & histología , Red Nerviosa/citología , Red Nerviosa/fisiología , Vías Nerviosas/anatomía & histología , Vías Nerviosas/citología , Vías Nerviosas/fisiología , Sinapsis/fisiología , Alas de Animales/inervación , Alas de Animales/fisiología
13.
J Exp Biol ; 227(13)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38842008

RESUMEN

In this report, passive elasticity properties of Octopus rubescens arm tissue are investigated using a multidisciplinary approach encompassing biomechanical experiments, computational modeling, and analyses. Tensile tests are conducted to obtain stress-strain relationships of the arm under axial stretch. Rheological tests are also performed to probe the dynamic shear response of the arm tissue. Based on these tests, comparisons against three different viscoelasticity models are reported.


Asunto(s)
Elasticidad , Octopodiformes , Animales , Octopodiformes/fisiología , Fenómenos Biomecánicos , Viscosidad , Extremidades/fisiología , Resistencia a la Tracción , Reología , Estrés Mecánico
14.
Curr Biol ; 34(13): 2812-2830.e5, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38861987

RESUMEN

During locomotion, most vertebrates-and invertebrates such as Drosophila melanogaster-are able to quickly adapt to terrain irregularities or avoid physical threats by integrating sensory information along with motor commands. Key to this adaptability are leg mechanosensory structures, which assist in motor coordination by transmitting external cues and proprioceptive information to motor centers in the central nervous system. Nevertheless, how different mechanosensory structures engage these locomotor centers remains poorly understood. Here, we tested the role of mechanosensory structures in movement initiation by optogenetically stimulating specific classes of leg sensory structures. We found that stimulation of leg mechanosensory bristles (MsBs) and the femoral chordotonal organ (ChO) is sufficient to initiate forward movement in immobile animals. While the stimulation of the ChO required brain centers to induce forward movement, unexpectedly, brief stimulation of leg MsBs triggered a fast response and sustained motor activity dependent only on the ventral nerve cord (VNC). Moreover, this leg-MsB-mediated movement lacked inter- and intra-leg coordination but preserved antagonistic muscle activity within joints. Finally, we show that leg-MsB activation mediates strong avoidance behavior away from the stimulus source, which is preserved even in the absence of a central brain. Overall, our data show that mechanosensory stimulation can elicit a fast motor response, independently of central brain commands, to evade potentially harmful stimuli. In addition, it sheds light on how specific sensory circuits modulate motor control, including initiation of movement, allowing a better understanding of how different levels of coordination are controlled by the VNC and central brain locomotor circuits.


Asunto(s)
Drosophila melanogaster , Locomoción , Animales , Drosophila melanogaster/fisiología , Locomoción/fisiología , Mecanorreceptores/fisiología , Actividad Motora/fisiología , Reacción de Prevención/fisiología , Extremidades/fisiología , Optogenética , Femenino
15.
Ann Anat ; 255: 152288, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38823491

RESUMEN

BACKGROUND: The regenerative capacity of organisms declines throughout evolution, and mammals lack the ability to regenerate limbs after injury. Past approaches to achieving successful restoration through pharmacological intervention, tissue engineering, and cell therapies have faced significant challenges. OBJECTIVES: This review aims to provide an overview of the current understanding of the mechanisms behind animal limb regeneration and the successful translation of these mechanisms for human tissue regeneration. RESULTS: Particular attention was paid to the Mexican axolotl (Ambystoma mexicanum), the only adult tetrapod capable of limb regeneration. We will explore fundamental questions surrounding limb regeneration, such as how amputation initiates regeneration, how the limb knows when to stop and which parts to regenerate, and how these findings can apply to mammalian systems. CONCLUSIONS: Given the urgent need for regenerative therapies to treat conditions like diabetic foot ulcers and trauma survivors, this review provides valuable insights and ideas for researchers, clinicians, and biomedical engineers seeking to facilitate the regeneration process or elicit full regeneration from partial regeneration events.


Asunto(s)
Ambystoma mexicanum , Extremidades , Regeneración , Animales , Humanos , Regeneración/fisiología , Extremidades/fisiología , Ambystoma mexicanum/fisiología , Investigación Biomédica Traslacional , Ingeniería de Tejidos/métodos , Medicina Regenerativa/métodos , Medicina Regenerativa/tendencias , Amputación Quirúrgica
16.
Curr Biol ; 34(12): R568-R570, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38889677

RESUMEN

Experimental, modeling, and robotic research shows that switching of sea stars from crawling to bouncing gaits does not require centralized neural control. Bouncing can instead arise cooperatively, with synchronization of sea star tube feet occurring by locally acting mechanisms alone.


Asunto(s)
Estrellas de Mar , Animales , Estrellas de Mar/fisiología , Extremidades/fisiología , Marcha/fisiología , Locomoción/fisiología , Robótica
17.
Biol Rev Camb Philos Soc ; 99(5): 1868-1888, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38817123

RESUMEN

The ability to regenerate large body appendages is an ancestral trait of vertebrates, which varies across different animal groups. While anamniotes (fish and amphibians) commonly possess this ability, it is notably restricted in amniotes (reptiles, birds, and mammals). In this review, we explore the factors contributing to the loss of regenerative capabilities in amniotes. First, we analyse the potential negative impacts on appendage regeneration caused by four evolutionary innovations: advanced immunity, skin keratinization, whole-body endothermy, and increased body size. These innovations emerged as amniotes transitioned to terrestrial habitats and were correlated with a decline in regeneration capability. Second, we examine the role played by the loss of regeneration-related enhancers and genes initiated by these innovations in the fixation of an inability to regenerate body appendages at the genomic level. We propose that following the cessation of regenerative capacity, the loss of highly specific regeneration enhancers could represent an evolutionarily neutral event. Consequently, the loss of such enhancers might promptly follow the suppression of regeneration as a side effect of evolutionary innovations. By contrast, the loss of regeneration-related genes, due to their pleiotropic functions, would only take place if such loss was accompanied by additional evolutionary innovations that compensated for the loss of pleiotropic functions unrelated to regeneration, which would remain even after participation of these genes in regeneration was lost. Through a review of the literature, we provide evidence that, in many cases, the loss in amniotes of genes associated with body appendage regeneration in anamniotes was significantly delayed relative to the time when regenerative capability was lost. We hypothesise that this delay may be attributed to the necessity for evolutionary restructuring of developmental mechanisms to create conditions where the loss of these genes was a beneficial innovation for the organism. Experimental investigation of the downregulation of genes involved in the regeneration of body appendages in anamniotes but absent in amniotes offers a promising avenue to uncover evolutionary innovations that emerged from the loss of these genes. We propose that the vast majority of regeneration-related genes lost in amniotes (about 150 in humans) may be involved in regulating the early stages of limb and tail regeneration in anamniotes. Disruption of this stage, rather than the late stage, may not interfere with the mechanisms of limb and tail bud development during embryogenesis, as these mechanisms share similarities with those operating in the late stage of regeneration. Consequently, the most promising approach to restoring regeneration in humans may involve creating analogs of embryonic limb buds using stem cell-based tissue-engineering methods, followed by their transfer to the amputation stump. Due to the loss of many genes required specifically during the early stage of regeneration, this approach may be more effective than attempting to induce both early and late stages of regeneration directly in the stump itself.


Asunto(s)
Evolución Biológica , Regeneración , Vertebrados , Animales , Vertebrados/fisiología , Vertebrados/genética , Regeneración/genética , Regeneración/fisiología , Extremidades/fisiología
18.
Cell Reprogram ; 26(3): 91-92, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38717852

RESUMEN

Cellular senescence is a state in which cells enter cell cycle arrest. However, senescent cells have the ability to secrete signaling molecules such as chemokines, cytokines, and growth factors. This secretory activity is an important feature of senescent cells, since the secreted factors impact the surrounding cellular microenvironment. Indeed, senescent cells and their secretome play a crucial role during limb development. However, whether the process of limb regeneration also relies on senescent cells remains unclear. Creation of a novel targeted depletion strategy that can eliminate senescent cells in the regenerating limb has now demonstrated an important role for senescent cells in limb regeneration. This role is linked to senescent cell-derived Wnt signaling. These findings reveal a previously unknown role for senescent cells during limb regeneration through Wnt signaling.


Asunto(s)
Senescencia Celular , Extremidades , Regeneración , Vía de Señalización Wnt , Extremidades/fisiología , Animales , Humanos
19.
Nat Commun ; 15(1): 3340, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38649703

RESUMEN

During organ regeneration, after the initial responses to injury, gene expression patterns similar to those in normal development are reestablished during subsequent morphogenesis phases. This supports the idea that regeneration recapitulates development and predicts the existence of genes that reboot the developmental program after the initial responses. However, such rebooting mechanisms are largely unknown. Here, we explore core rebooting factors that operate during Xenopus limb regeneration. Transcriptomic analysis of larval limb blastema reveals that hoxc12/c13 show the highest regeneration specificity in expression. Knocking out each of them through genome editing inhibits cell proliferation and expression of a group of genes that are essential for development, resulting in autopod regeneration failure, while limb development and initial blastema formation are not affected. Furthermore, the induction of hoxc12/c13 expression partially restores froglet regenerative capacity which is normally very limited compared to larval regeneration. Thus, we demonstrate the existence of genes that have a profound impact alone on rebooting of the developmental program in a regeneration-specific manner.


Asunto(s)
Extremidades , Regulación del Desarrollo de la Expresión Génica , Proteínas de Homeodominio , Regeneración , Proteínas de Xenopus , Xenopus laevis , Animales , Proliferación Celular/genética , Extremidades/fisiología , Edición Génica , Perfilación de la Expresión Génica , Proteínas de Homeodominio/metabolismo , Proteínas de Homeodominio/genética , Larva/crecimiento & desarrollo , Larva/genética , Regeneración/genética , Regeneración/fisiología , Proteínas de Xenopus/metabolismo , Proteínas de Xenopus/genética , Masculino , Femenino
20.
Dev Growth Differ ; 66(4): 285-296, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38600055

RESUMEN

The northern house gecko Hemidactylus flaviviridis exhibits appendage-specific responses to injuries. The autotomized tail regenerates, whereas the severed limb fails to regrow. Many site-specific cellular processes influence tail regeneration. Herein, we analyzed the epithelial-mesenchymal transition contrast in the lizard's amputated appendages (tail and limb). Morphological observations in the healing frame indicated the formation of regeneration blastema in the tail and scar formation in limb. Histology of the tail showed that epithelial cells closer to mesenchyme appeared less columnar and loosely packed, with little intercellular matrix. Whereas in the limb, the columnar epithelial cells remained tightly packed. Collagen deposition was seen in the limb at the intersection of wound epithelium and mesenchyme, favoring scarring by blocking the epithelial-mesenchymal transition. Markers for epithelial-mesenchymal transition were assessed at transcript and protein levels. The regenerating tail showed upregulation of N-cadherin, vimentin, and PCNA, favoring epithelial-mesenchymal transition, cell migration, and proliferation, respectively. In contrast, the scarring limb showed persistently elevated levels of E-cadherin and EpCAM, indicating retention of epithelial characteristics. An attempt was made to screen the resident epithelial stem cell population in both appendages to check their potential role in the epithelial-mesenchymal transition (EMT), hence the differential wound healing. Upregulation in transcript and protein levels of Nanog and Sox2 was observed in the regenerating tail. Fluorescence-activated cell sorting (FACS) provided supporting evidence that the epithelial stem cell population in tail remained significantly higher than in limb. Thus, this study focuses on the mechanistic role of the epithelial-mesenchymal transition in wound healing, highlighting the molecular details of regeneration and scarring events.


Asunto(s)
Transición Epitelial-Mesenquimal , Extremidades , Lagartos , Regeneración , Cola (estructura animal) , Animales , Lagartos/metabolismo , Transición Epitelial-Mesenquimal/fisiología , Extremidades/fisiología , Regeneración/fisiología , Amputación Quirúrgica
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