Functional joint regeneration is achieved using reintegration mechanism in Xenopus laevis

カエルではじめて機能的な関節の再生に成功. 京都大学プレスリリース. 2015-12-22.A functional joint requires integration of multiple tissues: the apposing skeletal elements should form an interlocking structure, and muscles should insert into skeletal tissues via tendons across the joint. Whereas newts can regenerate functional joints after amputation, Xenopus laevis regenerates a cartilaginous rod without joints, a “spike.” Previously we reported that the reintegration mechanism between the remaining and regenerated tissues has a significant effect on regenerating joint morphogenesis during elbow joint regeneration in newt. Based on this insight into the importance of reintegration, we amputated frogs’ limbs at the elbow joint and found that frogs could regenerate a functional elbow joint between the remaining tissues and regenerated spike. During regeneration, the regenerating cartilage was partially connected to the remaining articular cartilage to reform the interlocking structure of the elbow joint at the proximal end of the spike. Furthermore, the muscles of the remaining part inserted into the regenerated spike cartilage via tendons. This study might open up an avenue for analyzing molecular and cellular mechanisms of joint regeneration using Xenopus

Human Embryology

The study of human embryology has a very long history. Modern embryology owes its initial development to the key embryo collections that began in the 19th century. The first large collection was that of Carnegie, and this was followed later by the major 7 collections. The second role of the Carnegie collection was for researchers to establish a defined set of Carnegie stages based on embryo morphological features. Today, embryos are imaged three-dimensionally (3D) by a range of imaging modalities including, magnetic resonance microscopy (MRM), episcopic fluorescence image capture (EFIC), phase-contrast X-ray computed tomography (pCT), and optical projection tomography (OPT). Historically, embryo serial images were reconstructed using wax-plate and model techniques. The above new 3D imaging techniques now allow 3D computer reconstructions, analysis, and even 3D printing. This chapter will describe how the classical embryology collections and techniques have developed into today’s imaging and analysis techniques, giving new insights to human embryonic development

Congenital Anomalies in Human Embryos

Morphogenesis mainly occurs during embryonic stage, and congenital anomalies also occur at that time. The Kyoto Collection, one of the largest collections of human embryos, including a lot of those with congenital anomalies, is significantly helpful for analyzing embryonic growth. From the collection, normal and abnormal embryos have been selectively presented in this chapter. Recently developed imaging technology enabled three-dimensional (3D) imaging of embryos and fetuses in high resolution. The devices available for embryonic and fetal imaging and the results obtained therefrom are introduced in this chapter. In addition, new strategies for diagnosing congenital anomalies, such as autopsy imaging and genetic analyses, are discussed

Three-Dimensional Analysis of Human Laryngeal and Tracheobronchial Cartilages during the Late Embryonic and Early Fetal Period

Laryngeal and tracheobronchial cartilages are present as unique U-shaped forms around the respiratory tract and contribute to the formation of rigid structures required for the airway. Certain discrepancies still exist concerning cartilage formation in humans. To visualize the accurate timeline of cartilage formation, tracheobronchial and laryngeal cartilages were 3D reconstructed based on serial tissue sections during the embryonic period (Carnegie stage [CS] 18-23) and early fetal period (crown rump length [CRL] = 35-45 mm). The developmental phases of the cartilage were estimated by histological studies, which were performed on the reconstructed tissue sections. The hyoid greater horns were recognizable at CS18 (phase 2). Fusion of 2 chondrification centers in the mid-sagittal region was observed at CS19 in the hyoid bone, at CS20 in the cricoid cartilage, and in the specimen with CRL 39 mm in the thyroid cartilage. Phase 3 differentiation was observed at the median part of the hyoid body at CS19, which was the earliest among all other laryngeal and tracheobronchial cartilages. Most of the laryngeal cartilages were in phase 3 differentiation at CS22 and in phase 4 differentiation at CS23. The U-shaped tracheobronchial cartilages with phase 2 differentiation covered the entire extrapulmonary region at CS20. Phase 3 differentiation started on the median section and propagates laterally at CS21. The tracheobronchial cartilages may form simultaneously during the embryonic period at CS22-23 and early fetal periods, similar to adults in number and distribution. The spatial propagation of the tracheal cartilage differentiation provided in the present study indicates that cartilage differentiation may have propagated differently on phase 2 and phase 3. This study demonstrates a comprehensible timeline of cartilage formation. Such detailed information of the timeline of cartilage formation would be useful to improve our understanding of the development and pathophysiology of congenital airway anomalies

Morphogenesis of the Spleen During the Human Embryonic Period

We aimed to observe morphological changes in the spleen from the emergence of the primordium to the end of the embryonic period using histological serial sections of 228 samples. Between Carnegie stages (CSs) 14 and 17, the spleen was usually recognized as a bulge in the dorsal mesogastrium (DM), and after CS 20, the spleen became apparent. Intrasplenic folds were observed later. A high-density area was first recognized in 6 of the 58 cases at CS 16 and in all cases examined after CS 18. The spleen was recognized neither as a bulge nor as a high-density area at CS 13. The mesothelium was pseudostratified until CS 16 and was replaced with high columnar cells and then with low columnar cells. The basement membrane was obvious after CS 17. The mesenchymal cells differentiated from cells in the DM, and sinus formation started at CS 20. Hematopoietic cells were detected after CS 18. The vessels were observed at CS 14 in the DM. Hilus formation was observed after CS 20. The parallel entries of the arteries and veins were observed at CS 23. The rate of increase in spleen length in relation to that of stomach length along the cranial-caudal direction was 0.51±0.11, which remained constant during CSs 19 and 23, indicating that their growths were similar. These data may help to better understand the development of normal human embryos and to detect abnormal embryos in the early stages of development

Development of Helical Myofiber Tracts in the Human Fetal Heart: Analysis of Myocardial Fiber Formation in the Left Ventricle From the Late Human Embryonic Period Using Diffusion Tensor Magnetic Resonance Imaging

ヒト胎児心臓の心筋線維方向を追跡 --受精後8週の心筋線維は成人と同じ配列をする--. 京都大学プレスリリース. 2020-10-09.Background: Detection of the fiber orientation pattern of the myocardium using diffusion tensor magnetic resonance imaging lags ≈12 weeks of gestational age (WGA) behind fetal myocardial remodeling with invasion by the developing coronary vasculature (8 WGA). We aimed to use diffusion tensor magnetic resonance imaging tractography to characterize the evolution of fiber architecture in the developing human heart from the later embryonic period. Methods and Results: Twenty human specimens (8–24 WGA) from the Kyoto Collection of Human Embryos and Fetuses, including specimens from the embryonic period (Carnegie stages 20–23), were used. Diffusion tensor magnetic resonance imaging data were acquired with a 7T magnetic resonance system. Fractional anisotropy and helix angle were calculated using standard definitions. In all samples, the fibers ran helically in an organized pattern in both the left and right ventricles. A smooth transmural change in helix angle values (from positive to negative) was detected in all 16 directions of the ventricles. This feature was observed in almost all small (Carnegie stage 23) and large samples. A higher fractional anisotropy value was detected at the outer side of the anterior wall and septum at Carnegie stage 20 to 22, which spread around the ventricular wall at Carnegie stage 23 and in the early fetal samples (11–12 WGA). The fractional anisotropy value of the left ventricular walls decreased in samples with ≥13 WGA, which remained low (≈0.09) in larger samples. Conclusions: From the human late embryonic period (from 8 WGA), the helix angle arrangement of the myocardium is comparable to that of the adult, indicating that the myocardial structure blueprint, organization, and integrity are already formed

Morphometric human embryonic brain features according to developmental stage

Objectives: The present study investigated linear, area, and volume measurements of human brain samples according to Carnegie stages (CS) in an attempt to select suitable morphometric features that reflect embryonic development. Methods: Using magnetic resonance imaging, we measured seven linear segments, three separate areas, and three regional volumes in 101 samples between CS13 and 23. Brain volume was determined via manual segmentation of the magnetic resonance image, whereby a formula was generated to estimate the volume of each linear measurement. Results: All parameters correlated with crown-rump length. Bitemporal length and mesencephalic height increased linearly according to the CS, and a high correlation between bitemporal length and both whole-brain (r=0.98) and prosencephalon (r=0.99) volumes was found when brain cavity volume was excluded. Conclusion: Morphometric data related to human embryonic stages are valuable for correcting and comparing sonographic data. The present approach may contribute to improvements in prenatal diagnostics by enabling the selection of more suitable measurements during early embryonic stages