Journal of Anatomy最新文献

Virtual microscopy is becoming increasingly common in both medical education and routine clinical practice. Virtual microscopy software is typically designed either for (1) training students in anatomy, histology, and histopathology, or (2) quantitative analysis-but not both simultaneously. QuPath is one of the most widely used software applications for histopathology image analysis in research and provides a comprehensive set of computational tools to evaluate histology slides. We have enhanced QuPath by developing a new extension, QuPath Edu, which adapts the software to function as an intuitive microanatomy learning environment. Additionally, we have created an entirely new, complementary software platform called OpenMicroanatomy, which provides an alternative way to access QuPath Edu teaching content through a web interface. These tools have been used in teaching of first year medical and dentistry students at the University of Oulu Medical Faculty, and we conducted a user survey for the Class of 2023 to assess the usability and student experience. In general, the introduced annotation and quiz features were appreciated by the students and the system usability of OpenMicroanatomy was considered excellent (SUS score 84.8). Together, these freely available tools enable teachers to develop and deploy innovative training material for anatomy, histopathology, quantitative analysis, and artificial intelligence in a wide range of contexts. This unique combination can provide the next generation of students with essential multidisciplinary skills.

Precise regulation of organ size and position is crucial for optimal organ function. Since the swim bladder is primarily responsible for buoyancy in teleosts, early development and subsequent inflation of the swim bladder should be appropriately controlled with the body growth. However, the underlying mechanism remains unclear. In this study, we show that the size and position of the swim bladder are physically constrained by the surrounding bones in zebrafish. Non-invasive micro-CT scanning revealed that the anterior edge of the swim bladder is largely attached to the os suspensorium, which is an ossicle extending medioventrally from the 4th centrum. Additionally, we observed that hoxc6a mutants, which lack the os suspensorium, exhibited an anterior projection of the swim bladder beyond the 4th vertebra. During the swim bladder development, we found that the counterclockwise rotation of the os suspensorium correlates with posterior regression of the swim bladder, suggesting that the os suspensorium pushes the swim bladder posteriorly into its proper position. Furthermore, our results revealed a close association between the posterior region of the swim bladder and the pleural ribs. In hoxaa cluster mutants with additional ribs, the swim bladder expanded posteriorly, accompanied by an enlarged body cavity. Taken together, our results demonstrate the importance of the surrounding bones in the robust regulation of swim bladder size and position in zebrafish.

The Weberian apparatus is a novel hearing adaptation that facilitates increased hearing sensitivity in otophysan fishes. The apparatus is a complex system composed of modifications to anterior vertebral elements, the inner ear, and the swim bladder. A critical piece of the system that often receives minor attention are the various ligaments that bridge these three regions. The most famous of the ligaments is the interossicular ligament, which connects the Weberian ossicle chain (scaphium-intercalarium-tripus). Several other ligaments are present, including the suspensor (tripus to parapophysis 4) and the triple ligament (tripus-os suspensorium-tunica externa). Here, by combining diffusible iodine-based contrast enhancement (DICE) and propagation phase-contrast synchrotron radiation micro-computed tomography (PPC-SRμCT) with classic histological methods, we shine new light on the first intercostal ligament (ICL1) and discuss its potential function in relation to the Weberian apparatus. ICL1 is nearly absent from the cypriniform literature, typically only mentioned in a general discussion together with other intercostal ligaments. This study examines the development and structure of ICL1 comparatively with the other definitive Weberian ligaments in the zebrafish (Danio rerio). We provide a comprehensive view of three-dimensional shape, development, and composition to generate hypotheses regarding potential functions of ICL1 within the greater Weberian apparatus. Given new detail presented herein regarding the structure of ICL1, modifications to rib 5 and parapophysis 4 for ICL1 attachment, and the alignment of ICL1 with the os suspensorium, we propose a supportive (anchoring) role of ICL1 to aid in minimizing non-optimal movement of the structures of the fourth vertebra. This addition would focus vibrations anteriorly through the ossicle chain with minimal signal loss in zebrafish and other species with similar Weberian apparatus morphologies. We conclude that ICL1 should be included in future analyses of Weberian apparatus function where ligaments are addressed.

Congenital heart disease (CHD) has an incidence of approximately 1%. Over the last decade, sequencing studies including large cohorts of individuals with CHD have begun to unravel the genetic mechanisms underpinning CHD. This includes the identification of variants in cyclin-dependent kinase 13 (CDK13), in individuals with syndromic CHD. CDK13 encodes a serine/threonine protein kinase. The cyclin partner of CDK13 is cyclin K; this complex is thought to be important in transcription and RNA processing. Pathogenic variants in CDK13 cause CDK13-related disorder in humans, characterised by intellectual disability and developmental delay, recognisable facial features, feeding difficulties and structural brain defects, with 35% of individuals having CHD. To obtain a greater understanding for the role that this essential protein kinase plays in embryonic heart development, we have analysed a presumed loss of function Cdk13 transgenic mouse model (Cdk13^tm1b). The homozygous mutants were embryonically lethal in most cases by E15.5. X-gal staining showed Cdk13 expression localised to developing facial regions, heart and surrounding areas at E10.5, whereas at E12.5, it was more widely present. In the E15.5 heart, staining was seen throughout. RT-qPCR showed significant reduction in Cdk13 transcript expression in homozygous compared with WT and heterozygous hearts at E10.5 and E12.5. Detailed morphological 3D analysis of embryonic and postnatal hearts was performed using high-resolution episcopic microscopy, which affords a more detailed analysis of structures such as cardiac valve leaflets and endocardial cushions, compared with more traditional histological techniques. We show that both the homozygous and heterozygous Cdk13^tm1b mutants exhibit a range of CHD, including ventricular septal defects, bicuspid aortic valve, double outlet right ventricle and atrioventricular septal defects. 100% (n = 4) of homozygous hearts displayed CHD. Differential expression was seen in Cdk13^tm1b homozygous mutants for two genes known to be necessary for normal heart development. The types of defects, and the presence of CHD in heterozygous mice (17.02%, n = 8/47), are consistent with the CDK13-related disorder phenotype in humans. This study provides important insights into the effects of reduced function of CDK13 in the mouse heart and contributes to our understanding of the mechanism behind this disorder as a cause of CHD.

A variety of anatomical techniques, imaging modalities, dyes and contrast agents, were used to document the mechanisms/routes whereby spinal cerebrospinal fluid (CSF) would move beyond the confines of the spinal dura in the American alligator, Alligator mississippiensis. Three pathways for CSF loss were identified: spinal arachnoid granulations, perineural flow along the spinal nerves, and lymphatic drainage (both along the surface of the dura and at the venous plexus surrounding the spinal ganglion). These same three pathways for spinal CSF loss have been documented in mammals, suggesting that they may be a common feature of (at least) amniotes. Crocodilians, including A. mississippiensis, have the largest epidural venous sinus system of any vertebrate, the present study suggests that, as in mammals, the venous complex of the alligator plays a direct role in regulating the absorption of CSF from the spinal compartment.

The sacroiliac joint (SIJ) exhibits significant variation in auricular surface morphology. This variation influences the mechanics of the SIJ, a central node for transmitting mechanical energy from upper body to lower limbs and vice versa. The impact of the auricular surface morphology on stress and deformation in the SIJ remains poorly understood to date. Computed tomography scans obtained from 281 individuals were included to extract the geometry of the pelvic ring. Then, the auricular surface area, SIJ cartilage thickness, and total SIJ cartilage volume were identified. Based on these reconstructions, 281 finite element models were created to simulate SIJ mechanical loading. It was found that SIJ cartilage thickness only weakly depended on age or laterality, while being strongly sex sensitive. Auricular surface area and SIJ cartilage volume depended weakly and non-linearly on age, peaking around menopause in females, but without significant laterality effect. Larger SIJs, characterized by greater auricular area and cartilage volume, exhibited reduced stress and deformation under loading. These findings highlight the significant role of SIJ morphology in its biomechanical response, suggesting a potential link between morphological variations and the risk of SIJ dysfunction. Understanding this relationship could improve diagnosis and targeted treatment strategies for SIJ-related conditions.

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Cover image: see M. Didziokas et al., ‘BounTI (Boundary-preserving Threshold Iteration): a user-friendly tool for automatic hard tissue segmentation’, this issue.

Ankylosaurs were a group of heavily armored non-avian dinosaurs (Dinosauria, Ankylosauria), represented by a relatively abundant fossil record from the Cretaceous of North and South America. Their dermal skeleton was characterized by large osteoderms whose development and functional role have been largely investigated. However, interstitial small ossicles, forming between these osteoderms, have been far more overlooked and it remains unknown whether they were formed through the ossification of a preexisting fibrous matrix of connective tissue (i.e., metaplasia) or by a cell-induced differentiation of new fiber bundles followed by mineralization (i.e., neoplasia sensu (Zeitschrift für Wissenschaftliche Zoologie, 1858, 9, 147)). Here, we propose a hypothesis on the developmental origin of these small ossicles in the ankylosaurian Antarctopelta oliveroi using light microcopy, scanning electron microscopy and three-dimensional virtual histology through propagation phase-contrast synchrotron radiation micro-computed tomography (PPC-SRμCT). Ossicles are located in the dermis. They are composed of two layers: (1) a thin external layer, and (2) a thick basal plate, composed of collagen fiber bundles, which forms the main part of the ossicle. The external layer is made of a smooth, vitreous mineralized tissue that does not look like bone. The basal plate, however, is of osseous origin. In this basal plate, the collagen fiber bundles are organized in two orthogonal systems: one horizontal-observable in cross-sections-and one vertical-observable in the primary plane of sections sensu (Journal of Vertebrate Paleontology, 2004, 24, 874). The horizontal system is itself composed of successive layers of collagen fiber bundles arranged into an orthogonal plywood-like structure. The bundles of the vertical system radiate from the center of the ossicle at the level of the transition between the external layer and the basal plate and run towards the periphery of the basal plate. Their thickness increases from the center of the ossicle towards its periphery. Numerous bundles of the vertical system form thin threads that interweave and penetrate within the thick bundles of the horizontal system. Our new data suggest that the ossicles were at least partially formed by metaplasia, that is, through the ossification of a preexisting fibrous matrix of connective tissue. This process was probably supplemented by a cell-induced differentiation of new fiber bundles laid down prior to their incorporation into the fibrous system and its mineralization. This process looks more akin to neoplasia sensu (Zeitschrift für Wissenschaftliche Zoologie, 1858, 9, 147) than to metaplasia. Consequently, metaplastic and neoplastic processes may coexist in these ossicles with a possible differential expression during ontogeny.