RESEARCH ARTICLE Morphogenesis of the femur at different stages of normal human development 1 1 1 1,2 3 Yuko Suzuki , Jun Matsubayashi , Xiang Ji , Shigehito Yamada , Akio YoneyamaID , 4 4 1 1 Hirohiko Imai , Tetsuya MatsudaID , Tomoki Aoyama , Tetsuya TakakuwaID * 1 Human Health Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 2 Congenital Anomaly Research Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 3 SAGA Light Source, Saga, Japan, 4 Department of Systems Science, Graduate School of Informatics, Kyoto University, Kyoto, Japan a1111111111 *
[email protected] a1111111111 a1111111111 a1111111111 a1111111111 Abstract The present study aimed to better characterize the morphogenesis of the femur from the embryonic to the early fetal periods. Sixty-two human fetal specimens (crown±rump length [CRL] range: 11.4±185 mm) from the Kyoto Collection were used for this study. The mor- OPEN ACCESS phogenesis and internal differentiation process of the femur were analyzed in 3D using Citation: Suzuki Y, Matsubayashi J, Ji X, Yamada phase-contrast X-ray computed tomography and magnetic resonance imaging. The carti- S, Yoneyama A, Imai H, et al. (2019) laginous femur was first observed at Carnegie stage 18. Major anatomical landmarks were Morphogenesis of the femur at different stages of formed prior to the initiation of ossification at the center of the diaphysis (CRL, 40 mm), as normal human development. PLoS ONE 14(8): e0221569. https://doi.org/10.1371/journal. described by Bardeen. The region with very high signal intensity (phase 5 according to Stre- pone.0221569 eter's classification; i.e., area described as cartilage disintegration) emerged at the center of Editor: JJ Cray Jr., Ohio State University, UNITED the diaphysis, which split the region with slightly low signal intensity (phase 4; i.e., cartilage STATES cells of maximum size) in fetuses with a CRL of 40.0 mm.