Growth of the normal skull vault and its alteration in craniosynostosis: insights from human genetics and experimental studies
Open accessAbstract
The mammalian skull vault is constructed principally from five bones: the paired frontals and parietals, and the unpaired interparietal. These bones abut at sutures, where most growth of the skull vault takes place. Sutural growth involves maintenance of a population of proliferating osteoprogenitor cells which differentiate into bone matrix‐secreting osteoblasts. Sustained function of the sutures as growth centres is essential for continuous expansion of the skull vault to accommodate the growing brain. Craniosynostosis, the premature fusion of the cranial sutures, occurs in 1 in 2500 children and often presents challenging clinical problems. Until a dozen years ago, little was known about the causes of craniosynostosis but the discovery of mutations in the MSX2 , FGFR1 , FGFR2 , FGFR3 , TWIST1 and EFNB1 genes in both syndromic and non‐syndromic cases has led to considerable insights into the aetiology, classification and developmental pathology of these disorders. Investigations of the biological roles of these genes in cranial development and growth have been carried out in normal and mutant mice, elucidating their individual and interdependent roles in normal sutures and in sutures undergoing synostosis. Mouse studies have also revealed a significant correspondence between the neural crest–mesoderm boundary in the early embryonic head and the position of cranial sutures, suggesting roles for tissue interaction in suture formation, including initiation of the signalling system that characterizes the functionally active suture.
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The greater genetic load in coronal synostosis probably reflects the coronal suture's distinct embryological origin, where neural crest-derived frontal bone meets cephalic mesoderm-derived parietal bone.
“The higher genetic load associated with coronal synostosis is likely to reflect the distinct embryological origin of the coronal suture, at the boundary between the developing frontal bone (neural crest origin) and parietal bone (cephalic mesoderm).8,40”
From Craniosynostosis (2011) · cites this paper as [40]
The sections on suture formation and the mesoderm–neural crest boundary describe the coronal suture as a boundary between neural crest-derived frontal tissue and mesodermal parietal tissue. The passages do not establish that coronal synostosis has a higher genetic load or that this boundary explains it. Page numbers were not provided in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe incidence of single suture synostosis increased noticeably and constantly in recent years, with a dynamic change in the frequency of subtypes.
“The incidence of single suture synostosis increased noticeable constant in recent years. Moreover, there is a dynamic change in the frequency of the different subtypes of this clinical picture at the same time [21–24].”
From Developments in diagnostic and surgical techniques in children with sagittal suture craniosynostosis: a systematic review spanning the last 30 years (2025) · cites this paper as [21]
The epidemiology section (page not provided) gives the prevalence of different craniosynostosis subtypes, but no comparison across years. Searches for increasing incidence and changing subtype frequencies found no passage addressing either claimed trend. (LLM, conf=0.74)
Experimental — accuracy not yet measured
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- Authors
- Morriss‐Kay, G. M., & Wilkie, A. O. M.
- Affiliations
- University of Oxford (GB)
- John Radcliffe Hospital (GB)
- ORCID
- Wilkie, Andrew O. M.
- Venue
- Journal of Anatomy
- Publisher
- Wiley
- Published
- 2005-11
- Volume
- 207
- Issue
- 5
- Pages
- 637-653
- ISSN
- 0021-8782 (ISSN-L)
- 1469-7580
- PMC
- PMC1571561
- OpenAlex
- W1607201914
- Cited by
- 483
- References
- 96
- Citations by year
- 2026: 15 · 2025: 14 · 2024: 24 · 2023: 24 · 2022: 22 · 2021: 26 · 2020: 20 · 2019: 19 · 2018: 28 · 2017: 30 · 2016: 26 · 2015: 28 · 2014: 28 · 2013: 31 · 2012: 27
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Anatomy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Craniofacial Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- craniosynostosis, cranial sutures, osteoprogenitor cells, osteogenic differentiation, FGFR1, FGFR2, FGFR3, Msx2, TWIST1, ephrin-B1, skull development, mouse model, syndromic craniosynostosis
- MeSH terms
- Animals, Cranial Sutures, Craniosynostoses, Genes, Homeobox, Humans, Mice, Mutant Strains, Morphogenesis, Mutation, Skull, Gene Expression Regulation, Developmental, Fetal Development, Mice
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