Musculoskeletal System - Skull Development
|Embryology - 15 Dec 2018 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Fetal Skull
- 4 Mandible Development
- 5 Neurocranium
- 6 Skull Views
- 7 Skull Fontanels and Sutures
- 8 Fetal Head Growth
- 9 Abnormalities
- 10 Skull Histology
- 11 Adult Skull
- 12 References
- 13 Additional Images
- 14 Terms
- 15 External Links
- 16 Glossary Links
The skull is a unique skeletal structure in several ways: embryonic cellular origin (neural crest and mesoderm), form of ossification (intramembranous and ) and flexibility (fibrous sutures). The cranial vault (which encloses the brain) bones are formed by intramembranous ossification. While the bones that form the base of the skull are formed by endochondral ossification.
- endochondral ossification - ethmoid, basi sphenoid, basi occipital, petrous temporal
- intramembranous ossification - facial skeleton (nasals, maxillae, premaxillae, zygomatic, mandible) and cranial vault (frontal, parietal, and squamous temporal)
The bones enclosing the brain have large flexible fibrous joints (sutures) which allow firstly the head to pass through the birth canal and secondly postnatal brain growth. (See also notes on Head Development) In humans, ossification within the skull continues postnatally, through puberty until mid 20's and in old age the sutures separating the vault plates are often completely ossified.
In the entire skeleton, early ossification occurs in the jaw and at the ends of long bones (More? see movie developing mouse). Osteoblasts manufacture bone and are derived from ectomesenchymal in origin. (More? see lineage below). Flexible fibrous sutures allow growth of the brain to be accomodated by calvarial plate growth. Recent studies have show that noggin (a BMP antagonist) is involved in closure of these sutures.
Developmentally and clinically there are several abnormalities associated with skull growth and palate development. These abnormalities can furthermore impact on other systems such as neural, sensory, respiratory and nutritional functions.
|1910 Textbook Skull | 1910 Textbook Skull Images | 1910 30mm Embryo Skull | 1921 Human Brain Vascular | 1923 Head Subcutaneous Plexus | 1919 21mm Embryo Skull | 1920 Human Embryo Head Size | 1921 43 mm Fetal Skull | 1915 The Monotreme Skull | Historic Disclaimer|
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Ege Ülgen, Pınar Kuru Bektaşoğlu, M Aydın Sav, Özge Can, Ayça Erşen Danyeli, Deniz Baycın Hızal, M Necmettin Pamir, Koray Özduman Meningiomas display a specific immunoexpression pattern in a rostrocaudal gradient: An analysis of 366 patients. World Neurosurg: 2018; PubMed 30503291
Holly E Weiss-Bilka, Justin A Brill, Matthew J Ravosa ##Title## PeerJ: 2018, 6;e5757 PubMed 30386695
S Di Carlo, F De Angelis, E Brauner, D Rosella, P Papi, G Pompa, L Saptefrati, A M Cimpian, G Ciobanu Histological and immunohistochemical evaluation of mandibular bone tissue regeneration. Int J Immunopathol Pharmacol: 2018, 32;2058738418798249 PubMed 30350738
Rabjot Rai, Lilian C Azih, Joe Iwanaga, Marios Loukas, Martin Mortazavi, Rod J Oskouian, R Shane Tubbs Tendinous Inscriptions of the Rectus Abdominis: A Comprehensive Review. Cureus: 2018, 10(8);e3100 PubMed 30338176
Nicolas Arboleda-Ariza, Juan Schilling, Luis Ernesto Arriola-Guillén, Gustavo Armando Ruíz-Mora, Yalil Augusto Rodríguez-Cárdenas, Aron Aliaga-Del Castillo Maxillary transverse dimensions in subjects with and without impacted canines: A comparative cone-beam computed tomography study. Am J Orthod Dentofacial Orthop: 2018, 154(4);495-503 PubMed 30268260
The Images below show the combined endochondral and intramembranous ossification that is occurring in early fetal development (week 12).
In the first 2 images the bone cartilage is shown in blue and the new bone in red.
Note the difference in appearance between the upper and lower jaw (maxilla and mandible), the currently cartilage base of the skull (chondrocranium) and the cranial vault (neurocranium).
Fetal head lateral view
Fetal head medial view
Fetal head section
| This mid-line section through the fetal head shows features of the developing skull and the brain, face and mouth.
Meckel's cartilage, located within the first pharyngeal arch mandibular prominence, forms a cartilage "template" besides which the mandible develops by the process of intramembranous ossification. It is important to note that this cartilage template does not ossify (endochondral ossification) but provides a transient structure where the mandible will form, and later degenerates.
See also the 1957 historic paper on temporomandibular joint development.
Embryonic and Fetal Mandible
Embryo 24 mm (outer aspect, about Carnegie stage 22)
Embryo 24 mm (inner aspect, about Carnegie stage 22)
Birth to Adult Mandible
- Mandible Development: Week 8 outer view | Week 8 inner view | Week 12 outer view | Week 12 inner view | Week 12 Head outer view | Week 12 Head inner view | Birth | Childhood | Adult | Old Age | Small Animation | Large Animation | Muscle Attachments | Mandible Ossification | 1909 Mandible | embryo 18 mm | embryo 24 mm | embryo 28 mm | fetus 43 mm | fetus 65 mm | fetus 55 mm | fetus 95 mm | human 18-24-95 mm | Skull Development | Head Development
- neural crest origin
- requires Msx1 and Dlx5
- paraxial mesoderm origin
|anterior view||superior view||lateral view||lateral view|
|showing anterior fontenelle, sutures, mandible||showing anterior fontenelle, sutures||showing suture, mandible||newborn skull|
Skull Fontanels and Sutures
The bones enclosing the brain have large flexible fibrous joints (sutures) which allow firstly the head to compress and pass through the birth canal and secondly to postnatally expand for brain growth. (More? Molecular Skull Sutures) These sutures gradually fuse at different times postnatally, firstly the metopic suture in infancy and the others much later. Abnormal fusion (synostosis) of any of the sutures will lead to a number of different skull defects, leading to disruption of brain development. (More? Abnormal Synostosis) In old age all these sutures are generally completely fused and ossified.
|The newborn skull has 6 fontanels (fontanelles) the most obvious are the anterior and posterior fontanels that close at different times postnatally.
Newborn Skull Fontanels (CT, vertex view)
At the molecular level, accelerated suture intramembranous ossification can be mediated through a dual role of β-catenin in both the expansion of osteoprogenitors and the maturation of osteoblasts. These researchers also show that disruption of Axin2/β-catenin signaling alters the regulation of the downstream transcription target, cyclin D1, in the canonical Wnt pathway.
Computed Tomography Views
Skull CT Vertex, later and basal views.
Sutures and Fontanels
metopic suture begins at nose and runs superiorly to meet sagittal suture and fuses during infancy (fusion beginning at 3 months and completes by 6 to 8 months of age) before all other cranial sutures.
Cranial Base Synchondroses
In the base of the skull there can also be found a number of synchondrosis, "cartilage sutures", that are the last to close and have a role in the ongoing growth of the postnatal skull. Synchondrosis is a type of cartilaginous joint in which the cartilage is usually converted into bone before adult life. It has been compared in appearance to a long bone growth plate, but is bipolar rather than unipolar in structure.
These sutures also lost at different times in postnatal development:
- Inter-sphenoidal – around birth
- Spheno-ethmoidal – 6-7 yrs
- Spheno-occipital – 12-15 yrs
Fetal Head Growth
There are several skull deformities caused by premature fusion (synostosis) of different developing skull sutures. Suture abnormalities are classified as either "simple" (only one suture involved) or "compound" (two or more sutures involved).
|| * craniosynostosis premature cranial suture fusion, results in an abnormal skull shape, blindness and mental retardation.
Attenuation of signaling pathways stimulated by pathologically activated FGF-receptor 2 mutants prevents craniosynostosis. "Craniosynostosis, the fusion of one or more of the sutures of the skull vault before the brain completes its growth, is a common (1 in 2,500 births) craniofacial abnormality, approximately 20% of which occurrences are caused by gain-of-function mutations in FGF receptors (FGFRs). ...These experiments show that attenuation of FGFR signaling by pharmacological intervention could be applied for the treatment of craniosynostosis or other severe bone disorders caused by mutations in FGFRs that currently have no treatment."
Dolichocephaly and scaphocephaly
| Dolichocephaly and scaphocephaly
(premature fusion of the sagittal suture)
Brachycephaly and anterior plagiocephaly
(Greek, brakhu = short) (Greek plagios = oblique)
- brachycephaly - premature bicoronal fusion
- anterior plagiocephaly - unicoronal fusion
Leads to a restriction of anterior-posterior calvarial growth and relatively unaffected biparietal growth.
(Greek, trigonos = three angles) This abnormality results from the premature fusion of the metopic suture occurring before 6 months (3-9 months) of age.
Images show oxycephaly from severe sagittal and coronal synostoses (arrowheads).
Craniofrontonasal syndrome (CFNS) is a human X-linked developmental disorder caused by a mutation in ephrin-B1 affecting mainly females. Characterised by abnormal development of cranial and nasal bones, craniosynostosis (premature coronal suture fusion), and other extracranial anomalies (limb polydactyly and syndactyly).
| (a) Facial view showing marked hypertelorism, divergent squint, and central nasal groove (subject age, 1 year).
|Craniofrontonasal syndrome||Links: OMIM - Craniofrontonasal Syndrome|
A histological image of a skull bone formation by Intramembranous ossification.
|Adult Skull MRI||Links:||Skull Development||- MRI|
- D'Antoni AV, Donaldson OI, Schmidt C, Macchi V, De Caro R, Oskouian RJ, Loukas M & Shane Tubbs R. (2017). A comprehensive review of the anterior fontanelle: embryology, anatomy, and clinical considerations. Childs Nerv Syst , 33, 909-914. PMID: 28396968 DOI.
- Homayounfar N, Park SS, Afsharinejad Z, Bammler TK, MacDonald JW, Farin FM, Mecham BH & Cunningham ML. (2015). Transcriptional analysis of human cranial compartments with different embryonic origins. Arch. Oral Biol. , 60, 1450-60. PMID: 26188427 DOI.
- Clendenning DE & Mortlock DP. (2012). The BMP ligand Gdf6 prevents differentiation of coronal suture mesenchyme in early cranial development. PLoS ONE , 7, e36789. PMID: 22693558 DOI.
- Haberland M, Mokalled MH, Montgomery RL & Olson EN. (2009). Epigenetic control of skull morphogenesis by histone deacetylase 8. Genes Dev. , 23, 1625-30. PMID: 19605684 DOI.
- Sisson BE & Topczewski J. (2009). Expression of five frizzleds during zebrafish craniofacial development. Gene Expr. Patterns , 9, 520-7. PMID: 19595791 DOI.
- Eswarakumar VP, Ozcan F, Lew ED, Bae JH, Tomé F, Booth CJ, Adams DJ, Lax I & Schlessinger J. (2006). Attenuation of signaling pathways stimulated by pathologically activated FGF-receptor 2 mutants prevents craniosynostosis. Proc. Natl. Acad. Sci. U.S.A. , 103, 18603-8. PMID: 17132737 DOI.
- Moffatt BC. The prenatal development of the human temporomandibular joint. (1957) Carnegie Instn. Wash. Publ. 611, Contrib. Embryol., 36: .
- Chung IH, Han J, Iwata J & Chai Y. (2010). Msx1 and Dlx5 function synergistically to regulate frontal bone development. Genesis , 48, 645-55. PMID: 20824629 DOI.
- Liu B, Yu HM & Hsu W. (2007). Craniosynostosis caused by Axin2 deficiency is mediated through distinct functions of beta-catenin in proliferation and differentiation. Dev. Biol. , 301, 298-308. PMID: 17113065 DOI.
- Mirando AJ, Maruyama T, Fu J, Yu HM & Hsu W. (2010). β-catenin/cyclin D1 mediated development of suture mesenchyme in calvarial morphogenesis. BMC Dev. Biol. , 10, 116. PMID: 21108844 DOI.
- Khanna PC, Thapa MM, Iyer RS & Prasad SS. (2011). Pictorial essay: The many faces of craniosynostosis. Indian J Radiol Imaging , 21, 49-56. PMID: 21431034 DOI.
- Twigg SR, Kan R, Babbs C, Bochukova EG, Robertson SP, Wall SA, Morriss-Kay GM & Wilkie AO. (2004). Mutations of ephrin-B1 (EFNB1), a marker of tissue boundary formation, cause craniofrontonasal syndrome. Proc. Natl. Acad. Sci. U.S.A. , 101, 8652-7. PMID: 15166289 DOI.
Shah M, Ross JS, VanDyke C, Rudick RA, Goodkin DE, Obuchowski N & Modic MT. (1992). Volume T1-weighted gradient echo MRI in multiple sclerosis patients. J Comput Assist Tomogr , 16, 731-6. PMID: 1522265
Stelnicki EJ, Mooney MP, Losken HW, Zoldos J, Burrows AM, Kapucu R & Siegel MI. (1997). Ultrasonic prenatal diagnosis of coronal suture synostosis. J Craniofac Surg , 8, 252-8; discussion 259-61. PMID: 9482048
Ocampo RV & Persing JA. (1994). Sagittal synostosis. Clin Plast Surg , 21, 563-74. PMID: 7813156
Vander Kolk CA & Carson BS. (1994). Lambdoid synostosis. Clin Plast Surg , 21, 575-84. PMID: 7813157
Weinzweig J, Kirschner RE, Farley A, Reiss P, Hunter J, Whitaker LA & Bartlett SP. (2003). Metopic synostosis: Defining the temporal sequence of normal suture fusion and differentiating it from synostosis on the basis of computed tomography images. Plast. Reconstr. Surg. , 112, 1211-8. PMID: 14504503 DOI.
Search July 2010 "Skull Development" All (15473) Review (1231) Free Full Text (1634)
Search Pubmed: Skull Development
|1910 Development of the Skeleton|
|1914 Human Fetus 40 mm Skull|
|1921 43 mm Fetal Skull|
|1918 Gray's Anatomy|
- anterior fontanel - developing skull region that closes by about 20 months postnatally.
- basion - anatomical region on the basiocciput located at the midpoint between the anterior margin and posterior margin (opisthion) of the foramen magnum.
- compound craniosynostosis premature suture fusion involving two or more sutures.
- craniosynostosis - (craniostenosis) the premature fusion of cranial sutures.
- dermatocranium - (membranous) skull calvarial vault develops from intramembranous ossification.
- harlequin eye - a term used to describe the prominent bilateral elliptical orbits of the skull seen in brachycephaly.
- endochondral ossification - bone formation from a pre-existing cartilage template, such as the chondrocranium.
- intramembranous ossification - bone formation from a membrane where no pre-existing cartilage is found, such as the calvarial vault component.
- neurocranium - the portion of the skull that surrounds the brain. Ossification of bones in cranial base (endochondral) and vault (intramembranous).
- opisthion - anatomical region located on the occipital bone, located at the midpoint of the posterior margin of the foramen magnum.
- posterior fontanel - developing skull region that closes by about 3 months postnatally.
- primary craniosynostosis - an intrinsic defect in a suture.
- secondary craniosynostosis - premature closure of normal sutures due to systemic and metabolic (hyperthyroidism, hypercalcemia, hypophosphatasia, vitamin D deficiency, renal osteodystrophy, Hurler's Syndrome, sickle cell disease and thalassemia) and those that can affect brain growth.
- simple craniosynostosis - premature fusion involving only one suture.
- synostosis - premature fusion.
- viscerocranium - facial skeleton and some anterior neck structures.
External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.
- PubMed Health Craniosynostosis
- Johns Hopkins Fetal Skull Collection (1918–1951) - collection was begun by Adolph Hans Schultz (1891–1976) - fetal, stillbirths, newborns, and infants up to approximately one year of age. Collection of 112 specimens was transferred to the Cleveland Museum of Natural History on a permanent loan in 1973.
|Johns Hopkins Fetal Skull Collection (1918–1951)|
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Cite this page: Hill, M.A. (2018, December 15) Embryology Musculoskeletal System - Skull Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Musculoskeletal_System_-_Skull_Development
- © Dr Mark Hill 2018, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G