Musculoskeletal System - Skull Development
|Embryology - 24 Oct 2017 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), form of ossification (intramembranous and endochondrial) 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 endochondrial ossification.
- endochondral - ethmoid, basi sphenoid, basi occipital, petrous temporal
- intramembranous - 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.
Firat Elmas, Bikash L Shrestha Eagle's Syndrome. N. Engl. J. Med.: 2017, 377(13);e18 PubMed 28953433
Salvatore Savasta, Giorgia Carlone, Riccardo Castagnoli, Francesca Chiappe, Francesco Bassanese, Roberta Piras, Vincenzo Salpietro, Valeria Brazzelli, Alberto Verrotti, Gian L Marseglia X-Linked Hypohidrotic Ectodermal Dysplasia: New Features and a Novel EDA Gene Mutation. Cytogenet. Genome Res.: 2017, 152(3);111-116 PubMed 28877528
Max A Tischfield, Caroline D Robson, Nicole M Gilette, Shek Man Chim, Folasade A Sofela, Michelle M DeLisle, Alon Gelber, Brenda J Barry, Sarah MacKinnon, Linda R Dagi, Jeremy Nathans, Elizabeth C Engle Cerebral Vein Malformations Result from Loss of Twist1 Expression and BMP Signaling from Skull Progenitor Cells and Dura. Dev. Cell: 2017; PubMed 28844842
Khari D Thompson, Holly E Weiss-Bilka, Elizabeth B McGough, Matthew J Ravosa Bone up: craniomandibular development and hard-tissue biomineralization in neonate mice. Zoology (Jena): 2017; PubMed 28807504
Ryan Rourke, Seth M Weinberg, Mary L Marazita, Noel Jabbour Diagnosing subtle palatal anomalies: Validation of video-analysis and assessment protocol for diagnosing occult submucous cleft palate. Int. J. Pediatr. Otorhinolaryngol.: 2017, 100;242-246 PubMed 28802381
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|
- Negar Homayounfar, Sarah S Park, Zahra Afsharinejad, Theodor K Bammler, James W MacDonald, Federico M Farin, Brigham H Mecham, Michael L Cunningham Transcriptional analysis of human cranial compartments with different embryonic origins. Arch. Oral Biol.: 2015, 60(9);1450-1460 PubMed 26188427
- Dawn E Clendenning, Douglas P Mortlock The BMP ligand Gdf6 prevents differentiation of coronal suture mesenchyme in early cranial development. PLoS ONE: 2012, 7(5);e36789 PubMed 22693558
- Michael Haberland, Mayssa H Mokalled, Rusty L Montgomery, Eric N Olson Epigenetic control of skull morphogenesis by histone deacetylase 8. Genes Dev.: 2009, 23(14);1625-30 PubMed 19605684
- Barbara E Sisson, Jacek Topczewski Expression of five frizzleds during zebrafish craniofacial development. Gene Expr. Patterns: 2009, 9(7);520-7 PubMed 19595791
- V P Eswarakumar, F Ozcan, E D Lew, J H Bae, F Tomé, C J Booth, D J Adams, I Lax, J Schlessinger Attenuation of signaling pathways stimulated by pathologically activated FGF-receptor 2 mutants prevents craniosynostosis. Proc. Natl. Acad. Sci. U.S.A.: 2006, 103(49);18603-8 PubMed 17132737 | PNAS Link
- Moffatt BC. The prenatal development of the human temporomandibular joint. (1957) Carnegie Instn. Wash. Publ. 611, Contrib. Embryol., 36: .
- Il-Hyuk Chung, Jun Han, Junichi Iwata, Yang Chai Msx1 and Dlx5 function synergistically to regulate frontal bone development. Genesis: 2010, 48(11);645-55 PubMed 20824629
- Bo Liu, Hsiao-Man Ivy Yu, Wei Hsu Craniosynostosis caused by Axin2 deficiency is mediated through distinct functions of beta-catenin in proliferation and differentiation. Dev. Biol.: 2007, 301(1);298-308 PubMed 17113065
- Anthony J Mirando, Takamitsu Maruyama, Jiang Fu, Hsiao-Man Ivy Yu, Wei Hsu β-catenin/cyclin D1 mediated development of suture mesenchyme in calvarial morphogenesis. BMC Dev. Biol.: 2010, 10;116 PubMed 21108844
- Paritosh C Khanna, Mahesh M Thapa, Ramesh S Iyer, Shashank S Prasad Pictorial essay: The many faces of craniosynostosis. Indian J Radiol Imaging: 2011, 21(1);49-56 PubMed 21431034 | PMC3056371 | Indian J Radiol Imaging.
- V P Eswarakumar, F Ozcan, E D Lew, J H Bae, F Tomé, C J Booth, D J Adams, I Lax, J Schlessinger Attenuation of signaling pathways stimulated by pathologically activated FGF-receptor 2 mutants prevents craniosynostosis. Proc. Natl. Acad. Sci. U.S.A.: 2006, 103(49);18603-8 PubMed 17132737
- Stephen R F Twigg, Rui Kan, Christian Babbs, Elena G Bochukova, Stephen P Robertson, Steven A Wall, Gillian M Morriss-Kay, Andrew O M Wilkie Mutations of ephrin-B1 (EFNB1), a marker of tissue boundary formation, cause craniofrontonasal syndrome. Proc. Natl. Acad. Sci. U.S.A.: 2004, 101(23);8652-7 PubMed 15166289 | PNAS Link
M Shah, J S Ross, C VanDyke, R A Rudick, D E Goodkin, N Obuchowski, M T Modic Volume T1-weighted gradient echo MRI in multiple sclerosis patients. J Comput Assist Tomogr: 1992, 16(5);731-6 PubMed 1522265
E J Stelnicki, M P Mooney, H W Losken, J Zoldos, A M Burrows, R Kapucu, M I Siegel Ultrasonic prenatal diagnosis of coronal suture synostosis. J Craniofac Surg: 1997, 8(4);252-8; discussion 259-61 PubMed 9482048
R V Ocampo, J A Persing Sagittal synostosis. Clin Plast Surg: 1994, 21(4);563-74 PubMed 7813156
C A Vander Kolk, B S Carson Lambdoid synostosis. Clin Plast Surg: 1994, 21(4);575-84 PubMed 7813157
M M Cohen Sutural biology and the correlates of craniosynostosis. Am. J. Med. Genet.: 1993, 47(5);581-616 PubMed 8266985
Jeffrey Weinzweig, Richard E Kirschner, Alexander Farley, Philip Reiss, Jill Hunter, Linton A Whitaker, Scott P Bartlett 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.: 2003, 112(5);1211-8 PubMed 14504503
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.
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Cite this page: Hill, M.A. 2017 Embryology Musculoskeletal System - Skull Development. Retrieved October 24, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Musculoskeletal_System_-_Skull_Development
- © Dr Mark Hill 2017, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G