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Harsha Shah, Maya Al-Memar, Bernadette de Bakker, Hanine Fourie, Christoph Lees, Tom Bourne. The first-trimester fetal central nervous system: a novel ultrasonographic perspective. Am J Obstet Gynecol. 2017 Aug;217(2):220-221.



The fetal central nervous system and, in particular, ventricular system, is usually difficult to examine in any great detail in the first trimester as it is rapidly changing. Furthermore, visualization of the anatomical complexity of the central nervous system is limited by image resolution. The technical challenges of imaging the fetal brain during the first trimester have been evidenced by the difficulty of implementing routine first-trimester examination of posterior fossa intracranial translucency as a screening test for open neural tube defects. A further limitation is that thorough knowledge of both sonoembryology and the use of 3D multiplanar reconstruction and analysis are required to obtain diagnostic 3D images.

Crystal Vue and Realistic Vue (Samsung-Medison, Republic of Korea) are image-contrast enhancement and rendering software particularly effective at enabling perception of depth while preserving context and surface information. As demonstrated in this case, they allow visualization of the entire fetal ventricular system in a completely new way and enable imaging of structures not usually seen using standard 2-dimensional or 3D methods. The relatively simple use of this software may help to improve our understanding of neurodevelopmental changes in the first trimester. In addition, it may provide insight into pathognomonic markers of ventricular system anomalies and thus enable identification and diagnosis of fetal central nervous system abnormalities well before the second trimester.

© 2017 American Journal of Obstetrics & Gynecology. All rights reserved.

PMID: 28578173

DOI: 10.1016/j.ajog.2017.05.053

Bernadette S. de Bakker, Stan Driessen, Bastiaan JD Boukens, Maurice JH van den Hoff, Roelof-Jan Oostra. Single-site neural tube closure in human embryos revisited. Clin Anat. 2017 Oct;30(7):988-999.



Since the multi-site closure theory was first proposed in 1991 as explanation for the preferential localizations of neural tube defects, the closure of the neural tube has been debated. Although the multi-site closure theory is much cited in clinical literature, single-site closure is most apparent in literature concerning embryology. Inspired by Victor Hamburgers (1900-2001) statement that "our real teacher has been and still is the embryo, who is, incidentally, the only teacher who is always right", we decided to critically review both theories of neural tube closure. To verify the theories of closure, we studied serial histological sections of 10 mouse embryos between 8.5 and 9.5 days of gestation and 18 human embryos of the Carnegie collection between Carnegie stage 9 (19-21 days) and 13 (28-32 days). Neural tube closure was histologically defined by the neuroepithelial remodeling of the two adjoining neural fold tips in the midline. We did not observe multiple fusion sites in neither mouse nor human embryos. A meta-analysis of case reports on neural tube defects showed that defects can occur at any level of the neural axis. Our data indicate that the human neural tube fuses at a single site and, therefore, we propose to reinstate the single-site closure theory for neural tube closure. We showed that neural tube defects are not restricted to a specific location, thereby refuting the reasoning underlying the multi-site closure theory.

© 2017 Clinical Anatomy. All rights reserved.

PMID: 28795440

DOI: 10.1002/ca.22977


de Bakker BSde Bakker HMSoerdjbalie-Maikoe VDikkers FG. The development of the human hyoid-larynx complex revisited. Laryngoscope. 2017 Dec 8. [Epub ahead of print]



OBJECTIVES/HYPOTHESIS: The hyoid-larynx complex is highly prone to anatomical variation. The etiology of anatomical variants such as Eagle's syndrome and the aberrant hyoid apparatus can be explained from embryonic development. Modern textbooks state that the hyoid bone body develops from the second and third pharyngeal arch cartilages, and that thyroid cartilage derives from the fourth and sixth arch cartilages. This description, however, is incompatible with various anatomical variants, and it is unclear whether it was based on observations in human embryos or on comparative embryology.

STUDY DESIGN: 14 human embryos from the Carnegie collection between Carnegie stage 17 and 23 (42-60 days) were selected based on their histological quality.

METHODS: Histological sections of the selected embryos were examined. Three-dimensional models were prepared in an interactive format. These anatomical models provide crucial spatial information and facilitate interpretation.

RESULTS: We observed a less-complicated development of the hyoid-larynx complex than is currently described in textbooks. The body of the hyoid bone originates from a single growth center, without overt contributions from second and third pharyngeal arch cartilages. The fourth and sixth arch cartilages were not detected in human embryos; the thyroid and cricoid cartilages develop as mesenchymal condensations in the neck region.

CONCLUSIONS: Despite new research techniques, theories about hyoid-larynx complex development from the beginning of the 20th century have not been refuted properly and can still be found in modern literature. Based on observations in human embryos, we propose a new and relatively simple description of the development of the hyoid-larynx complex to facilitate better understanding of the etiology of anatomical variants.

© 2017 The American Laryngological, Rhinological and Otological Society, Inc. All rights reserved.

PMID: 29219191

DOI: 10.1002/lary.26987


Bernadette S. de Bakker, Kees H. de Jong, Jaco Hagoort, Karel de Bree, Clara T. Besselink, Froukje E. C. de Kanter, Tyas Veldhuis, Babette Bais, Reggie Schildmeijer, Jan M. Ruijter, Roelof-Jan Oostra,

Vincent M. Christoffels, Antoon F. M. Moorman. An interactive three-dimensional digital atlas and quantitative database of human development. Science. 2016 Nov; 354(6315).



Current knowledge about human development is based on the description of a limited number of embryonic specimens published in original articles and textbooks, often more than 100 years ago. It is exceedingly difficult to verify this knowledge, given the restricted availability of human embryos. We created a three-dimensional digital atlas and database spanning the first 2 months of human development, based on analysis of nearly 15,000 histological sections of the renowned Carnegie Collection of human embryonic specimens. We identified and labeled up to 150 organs and structures per specimen and made three-dimensional models to quantify growth, establish changes in the position of organs, and clarify current ambiguities. The atlas provides an educational and reference resource for studies on early human development, growth, and congenital malformations.

© 2016 American Association for the Advancement of Science. All rights reserved.

PMID: 27884980

DOI: 10.1126/science.aag0053


Burger NBHaak MCDe Bakker BSAl Shaibani ZDe Groot CJChristoffels VMBekker MNSystematic analysis of the development of the ductus venosus in wild type mouse and human embryos. Early Hum Dev. 2013 Dec;89(12):1067-73. 


BACKGROUND: Doppler flow velocities of the ductus venosus are increasingly used to assess fetal increased nuchal translucency, growth-restriction and monochorionic twins, and might contribute to screening for cardiac defects. It is disputed whether a sphincter at the ductus venosus inlet actively regulates blood flow.

AIMS: This study aims to define the morphogenesis of the developing mouse and human ductus venosus and to address the existence of a sphincter.

STUDY DESIGN: The presence of endothelium, smooth muscle, elastic fibers and nerves in the ductus venosus of E10.5-15.5 mouse embryos and in three corresponding human embryos (CS16, CS19 and CS23) was examined using immunohistochemistry. Three-dimensional reconstructions of the ductus venosus of E11.5-15.5 mouse and CS14-23 human embryos were generated and examined.

RESULTS: The ductus venosus lumen was narrowed from ventral-caudal to dorsal-cranial in E13.5-15.5 mouse and CS16-23 human embryos. Mouse embryos showed positive endothelial Pecam1 expression from E11.5-15.5 and smooth muscle actin staining in the ventral-caudal part of the ductus venosus from E12.5-15.5. At all developmental stages, elastic fiber and nerve marker expression was not detected in the ductus venosus (Fig. 2). In human embryos endothelial Pecam1 and smooth muscle actin expression was found in the ductus venosus from CS16 and CS19 onwards. Elastic fiber and nerve marker expression was not detected in all stages (Fig. 4). Morphogenesis and staining results of the ductus venosus were similar in both species.

CONCLUSIONS: The ductus venosus lacks a sphincter at its inlet as no accumulation of smooth muscle cells, elastic fibers or nerve innervation was found in mouse embryos from E11.5-15.5 and in human embryos from CS14-23.

© 2013 Elsevier Ireland Ltd. All rights reserved.

PMID: 23978399

DOI: 10.1016/j.earlhumdev.2013.07.029


de Bakker BSde Jong KHHagoort JOostra RJMoorman AFTowards a 3-dimensional atlas of the developing human embryo: the Amsterdam experience. Reprod Toxicol. 2012 Sep;34(2):225-36. 


Knowledge of complex morphogenetic processes that occur during embryonic development is essential for understanding anatomy and to get insight in the pathogenesis of congenital malformations. Understanding these processes can be facilitated by using a three-dimensional (3D) developmental series of human embryos, which we aim to create in this project. Digital images of serial sections of 34 human embryos of the Carnegie Collection between Carnegie stages 7 (15-17 days) and 23 (56-60 days) are used to create 3D reconstructions of different organ systems. The software package Amira is used to align the sections and to create the 3D reconstructions. In this midway evaluation we show the first results of the atlas, containing 34 embryos with more than 13.500 manually annotated sections. The 3D models can be interactively viewed within a 3D-pdf. This will be the first complete digital 3D human embryology atlas of this size, containing all developing organ systems.

Supplementary 3D-PDF: Stage 16 human embryo (37-42 days of development).

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID: 22640940 


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