The chondrocranium provides the key initial support for the fetal brain, jaws and cranial sensory organs in all vertebrates. The patterns of shaping and growth of the chondrocranium set up species-specific development of the entire craniofacial complex. The 3D development of chondrocranium have been studied primarily in animal model organisms, such as mice or zebrafish. In comparison, very little is known about the full 3D human chondrocranium, except from drawings made by anatomists many decades ago. The knowledge of human-specific aspects of chondrocranial development are essential for understanding congenital craniofacial defects and human evolution. Here advanced microCT scanning was used that includes contrast enhancement to generate the first 3D atlas of the human fetal chondrocranium during the middle trimester (13 to 19 weeks). In addition, since cartilage and bone are both visible with the techniques used, the endochondral ossification of cranial base was mapped since this region is so critical for brain and jaw growth. The human 3D models are published as a scientific resource for human development.

Central European Institute of Technology Brno University of Technology Brno Czech Republic

Department of Evolutionary Biology University of Vienna Vienna Austria

Department of Neuroimmunology Center for Brain Research Medical University of Vienna Vienna Austria

Department of Physiology and Pharmacology Karolinska Institutet Stockholm Sweden

The Life Sciences Institute The University of British Columbia Vancouver Canada

See more in PubMed

Vandamme, T. Use of rodents as models of human diseases. Journal of Pharmacy and Bioallied Sciences6 (2014). PubMed PMC

Phifer-Rixey, M. & Nachman, M. Insights into mammalian biology from the wild house mouse Mus musculus. eLife4 (2015). PubMed PMC

Veldman M, Lin S. Zebrafish as a Developmental Model Organism for Pediatric Research. Pediatric Research. 2008;64:470–476. doi: 10.1203/PDR.0b013e318186e609. PubMed DOI

Radlanski R, Renz H. An atlas of prenatal development of the human orofacial region. European Journal of Oral Sciences. 2010;118:321–324. doi: 10.1111/j.1600-0722.2010.00756.x. PubMed DOI

Radlanski R, Renz H, Tsengelsaikhan N, Schuster F, Zimmermann C. The remodeling pattern of human mandibular alveolar bone during prenatal formation from 19 to 270mm CRL. Annals of Anatomy - Anatomischer Anzeiger. 2016;205:65–74. doi: 10.1016/j.aanat.2016.01.005. PubMed DOI

Smit J, et al. A three‐dimensional analysis of the development of cranial nerves in human embryos. Clinical Anatomy. 2022;35:666–672. doi: 10.1002/ca.23889. PubMed DOI PMC

de Bakker B, et al. An interactive three-dimensional digital atlas and quantitative database of human development. Science. 2016;354:1019–1028. doi: 10.1126/science.aag0053. PubMed DOI

Danescu A, Mattson M, Dool C, Diewert V, Richman J. Analysis of human soft palate morphogenesis supports regional regulation of palatal fusion. Journal of Anatomy. 2015;227:474–486. doi: 10.1111/joa.12365. PubMed DOI PMC

Kerwin J, et al. The HUDSEN Atlas: a three-dimensional (3D) spatial framework for studying gene expression in the developing human brain. Journal of Anatomy. 2010;217:289–299. doi: 10.1111/j.1469-7580.2010.01290.x. PubMed DOI PMC

Yamada S, Nakano S, Makishima H, Motoki T. Novel Imaging Modalities for Human Embryology and Applications in Education. The Anatomical Record. 2018;301:1004–1011. doi: 10.1002/ar.23785. PubMed DOI

Katsube M, et al. Quantitation of nasal development in the early prenatal period using geometric morphometrics and MRI: a new insight into the critical period of Binder phenotype. Prenatal Diagnosis. 2017;37:907–915. doi: 10.1002/pd.5106. PubMed DOI

Katsube M, et al. Analysis of facial skeletal asymmetry during foetal development using μCT imaging. Orthodontics & Craniofacial Research. 2019;22:199–206. doi: 10.1111/ocr.12304. PubMed DOI PMC

Katsube M, et al. Critical Growth Processes for the Midfacial Morphogenesis in the Early Prenatal Period. The Cleft Palate-Craniofacial Journal. 2019;56:1026–1037. doi: 10.1177/1055665619827189. PubMed DOI

Katsube, M. et al. A 3D analysis of growth trajectory and integration during early human prenatal facial growth. Scientific Reports11 (2021). PubMed PMC

Katsube M, Yamada S, Utsunomiya N, Morimoto N. Application of geometric morphometrics for facial congenital anomaly studies. Congenital Anomalies. 2022;62:88–95. doi: 10.1111/cga.12461. PubMed DOI

Nohara A, et al. Morphometric analysis of secondary palate development in human embryos. Journal of Anatomy. 2022;241:1287–1302. doi: 10.1111/joa.13745. PubMed DOI PMC

Utsunomiya, N. et al. The first 3D analysis of the sphenoid morphogenesis during the human embryonic period. Scientific Reports12 (2022). PubMed PMC

O, J. et al. Micro-computed tomography with contrast enhancement: An excellent technique for soft tissue examination in humans. PLOS ONE16 (2021). PubMed PMC

O, J., Kwon, H., Kim, S., Cho, T. & Yang, H. Use of Micro X-ray Computed Tomography with Phosphotungstic Acid Preparation to Visualize Human Fibromuscular Tissue. Journal of Visualized Experiments (2019) 10.3791/59752. PubMed

Vymazalová K, Vargová L, Zikmund T, Kaiser J. The possibilities of studying human embryos and foetuses using micro-CT: a technical note. Anatomical Science International. 2017;92:299–303. doi: 10.1007/s12565-016-0377-3. PubMed DOI

Goldstein J, et al. Earlier Evidence of Spheno-Occipital Synchondrosis Fusion Correlates with Severity of Midface Hypoplasia in Patients with Syndromic Craniosynostosis. Plastic and Reconstructive Surgery. 2014;134:504–510. doi: 10.1097/PRS.0000000000000419. PubMed DOI

Hecht J, Butler I. Neurologic Morbidity Associated With Achondroplasia. Journal of Child Neurology. 1990;5:84–97. doi: 10.1177/088307389000500203. PubMed DOI

Hecht J, Horton W, Reid C, Pyeritz R, Chakraborty R. Growth of the foramen magnum in achondroplasia. American Journal of Medical Genetics. 1989;32:528–535. doi: 10.1002/ajmg.1320320421. PubMed DOI

Johnsen S, Wilsgaard T, Rasmussen S, Sollien R, Kiserud T. Longitudinal reference charts for growth of the fetal head, abdomen and femur. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2006;127:172–185. doi: 10.1016/j.ejogrb.2005.10.004. PubMed DOI

Tesařová M, et al. Use of micro computed-tomography and 3D printing for reverse engineering of mouse embryo nasal capsule. Journal of Instrumentation. 2016;11:C03006. doi: 10.1088/1748-0221/11/03/C03006. DOI

Kaiser M, 2024. 3D atlas of the human fetal chondrocranium in the middle trimester. BioStudies. S-BSST1227 PubMed PMC

Tesařová M, et al. An interactive and intuitive visualisation method for X-ray computed tomography data of biological samples in 3D Portable Document Format. Scientific Reports. 2019;9:1–8. doi: 10.1038/s41598-019-51180-2. PubMed DOI PMC

Kaucka, M. et al. Oriented clonal cell dynamics enables accurate growth and shaping of vertebrate cartilage. eLife6 (2017). PubMed PMC

Kaucka, M. et al. Signals from the brain and olfactory epithelium control shaping of the mammalian nasal capsule cartilage. eLife7 (2018). PubMed PMC

Heude, E. et al. Unique morphogenetic signatures define mammalian neck muscles and associated connective tissues. eLife7 (2018). PubMed PMC

Comai, G. et al. Local retinoic acid signaling directs emergence of the extraocular muscle functional unit. PLOS Biology18 (2020). PubMed PMC

Schneider C, Rasband W, Eliceiri K. NIH Image to ImageJ: 25 years of image analysis. Nature Methods. 2012;9:671–675. doi: 10.1038/nmeth.2089. PubMed DOI PMC

MeshLab: an Open-Source Mesh Processing Tool. Sixth Eurographics Italian Chapter Conference 129-136 (2008).

Hess, R. The essential Blender: guide to 3D creation with the open source suite Blender. (No Starch Press, 2007).

Limaye, A. & Stock, S. Drishti: a volume exploration and presentation tool. in 85060X- 10.1117/12.935640.

3D atlas of the human fetal chondrocranium in the middle trimester