Talk:Head Development

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Cite this page: Hill, M.A. (2021, March 6) Embryology Head Development. Retrieved from

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Head Development

<pubmed limit=5>Head Development</pubmed>

Neck Development

<pubmed limit=5>Neck Development</pubmed>

Table - Structures derived from Arches

Pharyngeal Arch Nerve Artery Neural Crest
(Skeletal Structures)
Muscles Ligaments
trigeminal (CN V) maxillary artery (terminal branches) mandible, maxilla, malleus, incus muscles of mastication, mylohyoid, tensor tympanic, ant. belly digastric ant lig of malleus, sphenomandibular ligament
facial (CN VII) stapedial (embryonic)

corticotympanic (adult)

stapes, styloid process, lesser cornu of hyoid, upper part of body of hyoid bone muscles of facial expression, stapedius, stylohyoid, post. belly digastric stylohyoid ligament
3 glossopharyngeal (CN IX) common carotid, internal carotid arteries greater cornu of hyoid, lower part of body of hyoid bone stylopharyngeus
4 vagus (CN X) superior laryngeal branch part of aortic arch (left), part right subclavian artery (right) thyroid, cricoid, arytenoid, corniculate and cuneform cartilages crycothyroid, soft palate levator veli palatini (not tensor veli palatini)
6 vagus (CN X) recurrent laryngeal branch part of left pulmonary artery (left), part of right pulmonary artery (right) thyroid, cricoid, arytenoid, corniculate and cuneform cartilages larynx intrinsic muscles (not cricothyroid muscle)
Arch Nerve Artery Skeletal Structures Muscles Ligaments
trigeminal (V) part of maxillary artery (mainly lost) mandible, maxilla, malleus, incus muscles of mastication, mylohyoid, tensor tympanic, ant. belly digastric ant lig of malleus, sphenomandibular ligament
facial (VII) stapedial arteries stapes, styloid process, lesser cornu of hyoid, upper part of body of hyoid bone muscles of facial expression, stapedius, stylohyoid, post. belly digastric stylohyoid ligament
3 glossopharyngeal (IX) common carotid arteries, internal carotid arteries greater cornu of hyoid, lower part of body of hyoid bone stylopharyngeus
4 vagus (X) superior laryngeal branch part of aortic arch (left), part right subclavian artery (right) thyroid, cricoid, arytenoid, corniculate and cuneform cartilages crycothyroid, soft palate levator veli palatini (not tensor veli palatini)
6 vagus (X) recurrent laryngeal branch part of left pulmonary artery (left), forms part of right pulmonary artery (right) thyroid, cricoid, arytenoid, corniculate and cuneform cartilages larynx intrinsic muscles (not cricothyroid muscle)


Craniofacial development: discoveries made in the chicken embryo

Int J Dev Biol. 2018;62(1-2-3):97-107. doi: 10.1387/ijdb.170321ja.

Abramyan J1, Richman JM.


The aim of this review is to highlight some of the key contributions to our understanding of craniofacial research from work carried out with the chicken and other avian embryos. From the very first observations of neural crest cell migration to the fusion of the primary palate, the chicken has proven indispensable in facilitating craniofacial research. In this review we will look back to the premolecular studies where "cut and paste" grafting experiments mapped the fate of cranial neural crest cells, the role of different tissue layers in patterning the face, and more recently the contribution of neural crest cells to jaw size and identity. In the late 80's the focus shifted to the molecular underpinnings of facial development and, in addition to grafting experiments, various chemicals and growth factors were being applied to the face. The chicken is above all else an experimental model, inviting hands-on manipulations. We describe the elegant discoveries made by directly controlling signaling either in the brain, in the pharyngeal arches or in the face itself. We cover how sonic hedgehog (Shh) signals to the face and how various growth factors regulate facial prominence identity, growth and fusion. We also review abnormal craniofacial development and how several type of spontaneous chicken mutants shed new light on diseases affecting the primary cilium in humans. Finally, we bring out the very important role that the bird beak has played in understanding amniote evolution. The chicken, duck and quail have been and will continue to be used as experimental models to explore the evolution of jaw diversity and the morphological constraints of the vertebrate face. PMID: 29616744 DOI: 10.1387/ijdb.170321ja

MR Imaging of the Fetal Face: Comprehensive Review

Radiographics. 2018 Apr 13:170142. doi: 10.1148/rg.2018170142. [Epub ahead of print]

Nagarajan M1, Sharbidre KG1, Bhabad SH1, Byrd SE1.


The human face is a complex anatomic structure with an equally complex embryologic development. Derangement of the developmental process can result in various structural anomalies, which range from a mainly cosmetic deformity, such as cleft lip, to potentially life-threatening conditions such as arhinia. These anomalies (a) can occur as isolated anomalies; (b) can be associated with intracranial, spinal, or dental anomalies; or (c) can be a part of various syndromes, thus serving as diagnostic clues in such cases. Proper evaluation of fetal facial deformities can help in prognostication, family counseling, and prenatal or early postnatal intervention. Ultrasonography (US) is the first line of investigation in these cases. However, when US does not allow complete evaluation of these anomalies owing to its inherent limitations, magnetic resonance (MR) imaging allows comprehensive evaluation of the anomaly itself and also evaluation of various associations and the treatment approach. The embryology of the fetal facial structures is considered with regard to the MR imaging technique and the MR imaging anatomy. The MR imaging features of various structural anomalies are described and classified into six groups, namely, orofacial clefts, orbital anomalies, nasal anomalies, facial masses, external ear anomalies, and abnormal face shape or profile. Also, the key associations and relevant treatment implications are reviewed. The article provides a "one-stop shop" review of these unique disorders-from basic understanding of the embryology to applying the knowledge in clinical practice, helping the interprofessional team and the patients alike. ©RSNA, 2018. PMID: 29652578 DOI: 10.1148/rg.2018170142


Clarifying the anatomy of the fifth arch artery

Ann Pediatr Cardiol. 2016 Jan-Apr;9(1):62-7. doi: 10.4103/0974-2069.171392.

Gupta SK1, Gulati GS2, Anderson RH3.


The artery allegedly forming in the fifth pharyngeal arch has increasingly been implicated as responsible for various vascular malformations in patients with congenitally malformed hearts. Observations from studies on developing embryos, however, have failed to provide support to substantiate several of these inferences such that the very existence of the fifth arch artery remains debatable. To the best of our knowledge, in only a solitary human embryo has a vascular channel been found that truly resembled the artery of the fifth arch. Despite the meager evidence to support its existence, the fifth arch artery has been invoked to explain the morphogenesis of double-barreled aorta, some unusual forms of aortopulmonary communications, and abnormalities of the brachiocephalic arteries. In most of these instances, the interpretations have proved fallible when examined in the light of existing knowledge of cardiac development. In our opinion, there are more plausible alternative explanations for the majority of these descriptions. Double-barreled aorta is more likely to result from retention of the recently identified dorsal collateral channels while abnormalities of brachiocephalic arteries are better explained on the basis of extensive remodeling of aortic arches during fetal development. Some examples of aortopulmonary communications, nonetheless, may well represent persistence of the developing artery of the fifth pharyngeal arch. We here present one such case - a patient with tetralogy of Fallot and pulmonary atresia, in whom the fifth arch artery provided a necessary communication between the ascending aorta and the pulmonary arteries. In this light, we discuss the features we consider to be essential before attaching the tag of "fifth arch artery" to a candidate vascular channel. KEYWORDS: Bovine arch; cardiac development; double-barreled aorta; fifth arch artery

PMID 27011696 PMCID: PMC4782472 DOI: 10.4103/0974-2069.171392

The Nervous System Orchestrates and Integrates Craniofacial Development: A Review

Front Physiol. 2016 Feb 19;7:49. doi: 10.3389/fphys.2016.00049. eCollection 2016.

Adameyko I1, Fried K2.


Development of a head is a dazzlingly complex process: a number of distinct cellular sources including cranial ecto- and endoderm, mesoderm and neural crest contribute to facial and other structures. In the head, an extremely fine-tuned developmental coordination of CNS, peripheral neural components, sensory organs and a musculo-skeletal apparatus occurs, which provides protection and functional integration. The face can to a large extent be considered as an assembly of sensory systems encased and functionally fused with appendages represented by jaws. Here we review how the developing brain, neurogenic placodes and peripheral nerves influence the morphogenesis of surrounding tissues as a part of various general integrative processes in the head. The mechanisms of this impact, as we understand it now, span from the targeted release of the morphogens necessary for shaping to providing a niche for cellular sources required in later development. In this review we also discuss the most recent findings and ideas related to how peripheral nerves and nerve-associated cells contribute to craniofacial development, including teeth, during the post- neural crest period and potentially in regeneration. KEYWORDS: craniofacial; development; glia; nervous system; stem cell; tooth PMID 26924989


A Functional Perspective on the Embryology and Anatomy of the Cerebral Blood Supply

J Stroke. 2015 May;17(2):144-58. doi: 10.5853/jos.2015.17.2.144. Epub 2015 May 29.

Menshawi K1, Mohr JP1, Gutierrez J1.


The anatomy of the arterial system supplying blood to the brain can influence the development of arterial disease such as aneurysms, dolichoectasia and atherosclerosis. As the arteries supplying blood to the brain develop during embryogenesis, variation in their anatomy may occur and this variation may influence the development of arterial disease. Angiogenesis, which occurs mainly by sprouting of parent arteries, is the first stage at which variations can occur. At day 24 of embryological life, the internal carotid artery is the first artery to form and it provides all the blood required by the primitive brain. As the occipital region, brain stem and cerebellum enlarge; the internal carotid supply becomes insufficient, triggering the development of the posterior circulation. At this stage, the posterior circulation consists of a primitive mesh of arterial networks that originate from projection of penetrators from the distal carotid artery and more proximally from carotid-vertebrobasilar anastomoses. These anastomoses regress when the basilar artery and the vertebral arteries become independent from the internal carotid artery, but their persistence is not uncommon in adults (e.g., persistent trigeminal artery). Other common remnants of embryological development include fenestration or duplication (most commonly of the basilar artery), hypoplasia (typically of the posterior communicating artery) or agenesis (typically of the anterior communicating artery). Learning more about the hemodynamic consequence that these variants may have on the brain territories they supply may help understand better the underlying physiopathology of cerebral arterial remodeling and stroke in patients with these variants. KEYWORDS: Arterial variants; Cerebral arteries; Circle of willis; Embryology; Remodeling; Stroke

PMID 26060802

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Dynamic epithelia of the developing vertebrate face

Curr Opin Genet Dev. 2015 Mar 3;32C:66-72. doi: 10.1016/j.gde.2015.02.003. [Epub ahead of print]

Choe CP1, Crump JG2.


A segmental series of endoderm-derived pouch and ectoderm-derived cleft epithelia act as signaling centers in the developing face. Their precise morphogenesis is therefore essential for proper patterning of the vertebrate head. Intercellular adhesion and polarity are highly dynamic within developing facial epithelial cells, with signaling from the adjacent mesenchyme controlling both epithelial character and directional migration. Endodermal and ectodermal epithelia fuse to form the primary mouth and gill slits, which involves basement membrane dissolution, cell intercalations, and apoptosis, as well as undergo further morphogenesis to generate the middle ear cavity and glands of the neck. Recent studies of facial epithelia are revealing both core programs of epithelial morphogenesis and insights into the coordinated assembly of the vertebrate head. Copyright © 2015 Elsevier Ltd. All rights reserved.

PMID 25748249



Development and evolution of the vertebrate primary mouth

J Anat. 2013 Jan;222(1):79-99. doi: 10.1111/j.1469-7580.2012.01540.x. Epub 2012 Jul 16.

Soukup V1, Horácek I, Cerny R.


The vertebrate oral region represents a key interface between outer and inner environments, and its structural and functional design is among the limiting factors for survival of its owners. Both formation of the respective oral opening (primary mouth) and establishment of the food-processing apparatus (secondary mouth) require interplay between several embryonic tissues and complex embryonic rearrangements. Although many aspects of the secondary mouth formation, including development of the jaws, teeth or taste buds, are known in considerable detail, general knowledge about primary mouth formation is regrettably low. In this paper, primary mouth formation is reviewed from a comparative point of view in order to reveal its underestimated morphogenetic diversity among, and also within, particular vertebrate clades. In general, three main developmental modes were identified. The most common is characterized by primary mouth formation via a deeply invaginated ectodermal stomodeum and subsequent rupture of the bilaminar oral membrane. However, in salamander, lungfish and also in some frog species, the mouth develops alternatively via stomodeal collar formation contributed both by the ecto- and endoderm. In ray-finned fishes, on the other hand, the mouth forms via an ectoderm wedge and later horizontal detachment of the initially compressed oral epithelia with probably a mixed germ-layer derivation. A very intriguing situation can be seen in agnathan fishes: whereas lampreys develop their primary mouth in a manner similar to the most common gnathostome pattern, hagfishes seem to undergo a unique oropharyngeal morphogenesis when compared with other vertebrates. In discussing the early formative embryonic correlates of primary mouth formation likely to be responsible for evolutionary-developmental modifications of this area, we stress an essential role of four factors: first, positioning and amount of yolk tissue; closely related to, second, endoderm formation during gastrulation, which initiates the process and constrains possible evolutionary changes within this area; third, incipient structure of the stomodeal primordium at the anterior neural plate border, where the ectoderm component of the prospective primary mouth is formed; and fourth, the prime role of Pitx genes for establishment and later morphogenesis of oral region both in vertebrates and non-vertebrate chordates.

© 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.

PMID 22804777

Development of the platysma muscle and the superficial musculoaponeurotic system (human specimens at 8-17 weeks of development)

ScientificWorldJournal. 2013 Dec 12;2013:716962. doi: 10.1155/2013/716962. eCollection 2013.

De la Cuadra-Blanco C1, Peces-Peña MD2, Carvallo-de Moraes LO3, Herrera-Lara ME2, Mérida-Velasco JR1. Author information


There is controversy regarding the description of the different regions of the face of the superficial musculoaponeurotic system (SMAS) and its relationship with the superficial mimetic muscles. The purpose of this study is to analyze the development of the platysma muscle and the SMAS in human specimens at 8-17 weeks of development using an optical microscope. Furthermore, we propose to study the relationship of the anlage of the SMAS and the neighbouring superficial mimetic muscles. The facial musculature derives from the mesenchyme of the second arch and migrates towards the different regions of the face while forming premuscular laminae. During the 8th week of development, the cervical, infraorbital, mandibular, and temporal laminae are observed to be on the same plane. The platysma muscle derives from the cervical lamina and its mandibular extension enclosing the lower part of the parotid region and the cheek, while the SMAS derives from the upper region. During the period of development analyzed in this study, we have observed no continuity between the anlage of the SMAS and that of the superficial layer of the temporal fascia and the zygomaticus major muscle. Nor have we observed any structure similar to the SMAS in the labial region.

PMID 24396304

Clarification of the identity of the mammalian fifth pharyngeal arch artery

Clin Anat. 2013 Mar;26(2):173-82. doi: 10.1002/ca.22101. Epub 2012 May 23.

Bamforth SD, Chaudhry B, Bennett M, Wilson R, Mohun TJ, Van Mierop LH, Henderson DJ, Anderson RH. Source Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.


The remodeling of the pharyngeal arch arteries is a complex process that occurs across vertebrates, although the specific number of arteries varies across species, with six in fish, but only five in birds and mammals, although they are numbered one through four, and six. The existence of a fifth arch artery in mammals has been debated for more than a century. Although some have doubted, and continue to doubt, its existence, several cardiovascular malformations can be explained only on the basis of its presence. We have analyzed the developing pharyngeal arch arteries in mouse and human embryos, using high-resolution episcopic microscopy. We have then created three-dimensional models, allowing us to identify any structures that would satisfy the descriptions of fifth arch arteries. This detailed examination revealed collateral channels connecting the fourth and sixth pharyngeal arch arteries in approximately half of the mouse embryos examined. Such collateral channels were seen in only one human embryo of eight examined by high-resolution episcopic microscopy, although we had previously identified such collateral channels using wax plate reconstruction. An extra vessel, occupying a discrete component of the pharyngeal mesenchyme, and therefore resembling a true fifth pharyngeal arch artery, was observed in one Carnegie Stage 14 human embryo. The pharyngeal mesenchyme in the human, therefore, can contain a fifth arch, with a contained artery, albeit transiently. Persistence of this structure, and the observed collateral channels, provides mechanisms to explain the congenital cardiovascular malformations described as persistent fifth aortic arch, and double-barreled aorta. Copyright © 2012 Wiley Periodicals, Inc. PMID 22623372


Developmental and evolutionary origins of the pharyngeal apparatus

Evodevo. 2012 Oct 1;3(1):24. [Epub ahead of print]

Graham A, Richardson J. Abstract

ABSTRACT: The vertebrate pharyngeal apparatus, serving the dual functions of feeding and respiration, has its embryonic origin in a series of bulges found on the lateral surface of the head, the pharyngeal arches. Developmental studies have been able to discern how these structures are constructed and this has opened the way for an analysis of how the pharyngeal apparatus was assembled and modified during evolution. For many years, the role of the neural crest in organizing pharyngeal development was emphasized and, as this was believed to be a uniquely vertebrate cell type, it was suggested that the development of the pharyngeal apparatus of vertebrates was distinct from that of other chordates. However, it has now been established that a key event in vertebrate pharyngeal development is the outpocketing of the endoderm to form the pharyngeal pouches. Significantly, outpocketing of the pharyngeal endoderm is a basal deuterostome character and the regulatory network that mediates this process is conserved. Thus, the framework around which the vertebrate pharyngeal apparatus is built is ancient. The pharyngeal arches of vertebrates are, however, more complex and this can be ascribed to these structures being populated by neural crest cells, which form the skeletal support of the pharynx, and mesoderm, which will give rise to the musculature and the arch arteries. Within the vertebrates, as development progresses beyond the phylotypic stage, the pharyngeal apparatus has also been extensively remodelled and this has seemingly involved radical alterations to the developmental programme. Recent studies, however, have shown that these alterations were not as dramatic as previously believed. Thus, while the evolution of amniotes was believed to have involved the loss of gills and their covering, the operculum, it is now apparent that neither of these structures was completely lost. Rather, the gills were transformed into the parathyroid glands and the operculum still exists as an embryonic entity and is still required for the internalization of the posterior pharyngeal arches. Thus, the key steps in our phylogenetic history are laid out during the development of our pharyngeal apparatus.

PMID 23020903


Neonatal head ultrasound abnormalities in preterm infants and adolescent psychiatric disorders

Arch Gen Psychiatry. 2011 Jul;68(7):742-52.

Whitaker AH, Feldman JF, Lorenz JM, McNicholas F, Fisher PW, Shen S, Pinto-Martin J, Shaffer D, Paneth N. Source Unit 74, Division of Adolescent and Child Psychiatry, Columbia University Medical Center, New York State Psychiatric Institute, 1051 Riverside Dr, New York, NY 10032.


CONTEXT: Infants born prematurely are at risk for a perinatal encephalopathy characterized by white and gray matter injuries that affect subsequent cortical development and neural connectivity and potentially increase risk for later psychiatric disorder.

OBJECTIVE: To determine the relation of perinatal brain injury, as detected by neonatal head ultrasound, to psychiatric disorders in adolescents who were born prematurely.

DESIGN: Prospective cohort.

SETTING: Community.

PARTICIPANTS: Adolescent survivors of a population-based low-birth-weight (<2000 g; 96% preterm; born 1984-1987) cohort (n = 1105) screened as neonates with serial head ultrasounds. Neonatal head ultrasound abnormalities were categorized as either (1) germinal matrix and/or intraventricular hemorrhage or (2) parenchymal lesions and/or ventricular enlargement. Of 862 eligible survivors, 628 (72.9%) were assessed at age 16 years. The sample consisted of 458 nondisabled survivors assessed in person. Main Outcome Measure Adolescent current and lifetime psychiatric disorders assessed with parent report on the Diagnostic Interview Schedule for Children-IV.

RESULTS: Compared with no abnormality, germinal matrix/intraventricular hemorrhage increased risk for current major depressive disorder (odds ratio, 2.7; 95% confidence interval, 1.0-6.8) and obsessive-compulsive disorder (9.5; 3.0-30.1). Parenchymal lesions/ventricular enlargement increased risk for current attention-deficit/hyperactivity disorder-inattentive type (odds ratio, 7.6; 95% confidence interval, 2.0-26.5), tic disorders (8.4; 2.4-29.6), and obsessive-compulsive disorder (7.6; 1.39-42.0). Parenchymal lesions/ventricular enlargement were not related to lifetime attention-deficit/hyperactivity disorder-inattentive type, but all other relations were similar for lifetime disorders. Control for other early risk factors did not alter these relations. Most of these relations persisted with control for concurrent cognitive or motor problems.

CONCLUSION: In preterm infants, 2 distinct types of perinatal brain injury detectable with neonatal head ultrasound selectively increase risk in adolescence for psychiatric disorders in which dysfunction of subcortical-cortical circuits has been implicated.

PMID 21727256

The genetic basis of craniofacial and dental abnormalities

Schweiz Monatsschr Zahnmed. 2011;121(7-8):636-46.

Kouskoura T, Fragou N, Alexiou M, John N, Sommer L, Graf D, Katsaros C, Mitsiadis TA. Source University of Zurich, Institute of Oral Biology, Zurich, Switzerland.


The embryonic head development, including the formation of dental structures, is a complex and delicate process guided by specific genetic programs. Genetic changes and environmental factors can disturb the execution of these programs and result in abnormalities in orofacial and dental structures. Orofacial clefts and hypodontia/ oligodontia are examples of such abnormalities frequently seen in dental clinics. An insight into the mechanisms and genes involved in the formation of orofacial and dental structures has been gradually gained by genetic analysis of families and by the use of experimental vertebrate models such as the mouse and chick models. The development of novel clinical therapies for orofacial and dental pathological conditions depends very much on a detailed knowledge of the molecular and cellular processes that are involved in head formation.

PMID 21861247


The origin and early development of the nasal septum in human embryos

Ann Anat. 2010 Apr 20;192(2):82-5. Epub 2010 Jan 25.

Steding G, Jian Y. Source Centre of Anatomy, Georg August University Goettingen, Kreuzbergring 36, 37075 Goettingen, Germany.


Based on scanning electron microscopic dissections of human embryos and fetuses of the sixth to the twelfth week (Carnegie stages 16-23 and early fetus), the origin of the nasal septum was studied. The findings show that the nasal septum does not grow downwards. It is derived from the tissue between the primary choanae: as such, its anlage is present from the very beginning. Its contact and fusion with the palatal shelves is made possible by the elevation of the palatal shelves from the vertical into the horizontal position, as the tongue descends. Copyright 2010 Elsevier GmbH. All rights reserved.

PMID 20149609

The Meckel's cartilage in human embryonic and early fetal periods

Anat Sci Int. 2010 Aug 27.

Wyganowska-Świątkowska M, Przystańska A.

Department of Conservative Dentistry and Periodontology, Poznan University of Medical Sciences, 70 Bukowska Street, 60-812, Poznan, Poland, Abstract The Meckel's cartilage itself and the mandible are derived from the first branchial arch, and their development depends upon the contribution of the cranial neural crest cells. The prenatal development of the Meckel's cartilage, along with its relationship to the developing mandible and the related structures, were studied histologically in human embryos and fetuses. The material was obtained from a collection of the Department of Anatomy, and laboratory procedures were used to prepare sections, which were stained according to standard light-microscopy methods. The formation of the Meckel's cartilage and its related structures was observed and documented. Some critical moments in the development of the Meckel's cartilage are suggested. The sequential development of the Meckel's cartilage started as early as stage 13 (32 days) with the appearance of condensation of mesenchymal cells within the mandibular prominence. During stage 17 (41 days), the primary ossification center of the mandible appeared on the inferior margin of the Meckel's cartilage. The muscular attachments to the Meckel's cartilage in embryos were observed at stage 18 (44 days). Their subsequent movement into the developing mandible during the 10th week seemed to diminish the role of the Meckel's cartilage as the supportive core; simultaneously, the process of regression within the cartilage was induced. During the embryonic period, the bilateral Meckel's cartilages were in closest contact at the posterior surface of their superior margins, preceding formation of the symphyseal cartilage at this site. The event sequence in the development of the Meckel's cartilage is finally discussed.

PMID 20799009

Incidence and Development of the Human Supracochlear Cartilage

Cells Tissues Organs. 2010 Sep 28.

Mérida Velasco JR, Rodríguez Vázquez JF, de la Cuadra Blanco C, Sanz Casado JV, Mérida Velasco JA.

Departamento de Anatomía y Embriología Humana II, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain. Abstract

The supracochlear cartilage is known as an accessory cartilage of the chondrocranium situated between the otic capsule and the trigeminal ganglion. Although claimed to appear regularly during human development, its incidence and development have been reported only scarcely in the literature. The aim of this study was to describe the position and relationships of the supracochlear cartilage during its development. This study was made in 96 human specimens of 7-17 weeks of development, belonging to a collection of the Embryology Institute of Complutense University of Madrid. In addition, three-dimensional reconstruction of the supracochlear cartilage was made from 1 specimen. This cartilage, spherical in shape, appeared bilaterally in 23 specimens and unilaterally (left side) in 5. In our results, the supracochlear cartilage was found in 26.5% of the cases and was related to the trigeminal ganglion, the dura mater of the trigeminal cavity and the otic capsule. In 4 specimens, bilaterally, the supracochlear cartilage was continuous with the otic capsule. This work suggests that, based on the structures to which the supracochlear cartilage is related, it could be derived from the cranial neural crest.

PMID 20881354


The role of macrophages in the disappearance of Meckel's cartilage during mandibular development in mice

Tsuzurahara F, Soeta S, Kawawa T, Baba K, Nakamura M. Acta Histochem. 2009 Oct 22. [Epub ahead of print] PMID: 19853894


Roles of FGFR3 during morphogenesis of Meckel's cartilage and mandibular bones

Havens BA, Velonis D, Kronenberg MS, Lichtler AC, Oliver B, Mina M. Dev Biol. 2008 Apr 15;316(2):336-49. Epub 2008 Feb 13.

To address the functions of FGFR2 and FGFR3 signaling during mandibular skeletogenesis, we over-expressed in the developing chick mandible, replication-competent retroviruses carrying truncated FGFR2c or FGFR3c that function as dominant negative receptors (RCAS-dnFGFR2 and RCAS-dnFGFR3). Injection of RCAS-dnFGFR3 between HH15 and 20 led to reduced proliferation, increased apoptosis, and decreased differentiation of chondroblasts in Meckel's cartilage. These changes resulted in the formation of a hypoplastic mandibular process and truncated Meckel's cartilage. This treatment also affected the proliferation and survival of osteoprogenitor cells in osteogenic condensations, leading to the absence of five mandibular bones on the injected side. Injection of RCAS-dnFGFR2 between HH15 and 20 or RCAS-dnFGFR3 at HH26 did not affect the morphogenesis of Meckel's cartilage but resulted in truncations of the mandibular bones. RCAS-dnFGFR3 affected the proliferation and survival of the cells within the periosteum and osteoblasts. Together these results demonstrate that FGFR3 signaling is required for the elongation of Meckel's cartilage and FGFR2 and FGFR3 have roles during intramembranous ossification of mandibular bones.

PMID: 18339367


Signaling by bone morphogenetic proteins directs formation of an ectodermal signaling center that regulates craniofacial development

Dev Biol. 2007 Dec 1;312(1):103-14. Epub 2007 Sep 20.

Foppiano S, Hu D, Marcucio RS.

Department of Orthopaedic Surgery, San Francisco General Hospital, The University of California at San Francisco, School of Medicine, San Francisco, CA 94110, USA.

Abstract We previously described a signaling center, the Frontonasal Ectodermal Zone (FEZ) that regulates growth and patterning of the frontonasal process (FNP). The FEZ is comprised of FNP ectoderm flanking a boundary between Sonic hedgehog (Shh) and Fibroblast growth factor 8 (Fgf8) expression domains. Our objective was to examine BMP signaling during formation of the FEZ. We blocked BMP signaling throughout the FNP prior to FEZ formation by infecting chick embryos at stage 10 (HH10) with a replication-competent avian retrovirus encoding the BMP antagonist Noggin. We assessed gene expression patterns in the FNP 72 h after infection (approximately HH22) and observed that Shh expression was reduced or absent. In the mesenchyme, we observed that Bmp2 transcripts were absent while the Bmp4 expression domain was expanded proximally. In addition to the molecular changes, infected embryos also exhibited facial malformations at 72 and 96 h after infection suggesting that the FEZ did not form. Our data indicate that reduced cell proliferation, but not apoptosis, in the mesenchyme contributed to the phenotype that we observed. Additionally, adding exogenous SHH into the mesenchyme of RCAS-Noggin-infected embryos did not restore Bmp2 and Bmp4 to a normal pattern of expression. These data indicate that BMP signaling mediates interactions between tissues in the FNP that regulate FEZ formation; and that the correct pattern of Bmp2 and Bmp4, but not Bmp7, expression in the FNP mesenchyme requires signaling by the BMP pathway.

PMID 18028903

The development of Meckel's cartilage in staged human embryos during the 5th week

Folia Morphol (Warsz). 2005 Feb;64(1):23-8.

Lorentowicz-Zagalak M, Przystańska A, Woźniak W. Department of Anatomy, University School of Medical Sciences, 60-781 Poznán, Poland.

Abstract The study was conducted on 15 embryos aged 5 weeks. The primordium of Meckel's cartilage appears at stage 13 (32 days) as a rounded structure composed of fusiform and polygonal cells, which blend with other cells of the mandibular process. At stages 14 and 15 (33 and 36 days) Meckel's cartilage forms a well delineated core of small densely packed cells.

PMID 15832266


The role of the endoderm in the development and evolution of the pharyngeal arches

J Anat. 2005 Nov;207(5):479-87.

Graham A, Okabe M, Quinlan R. Source MRC Centre for Developmental Neurobiology, Guys Campus, Kings College London, London, UK.


The oro-pharyngeal apparatus has its origin in a series of bulges found on the lateral surface of the embryonic head, the pharyngeal arches. Significantly, the development of these structures is extremely complex, involving interactions between a number of disparate embryonic cell types: ectoderm, endoderm, mesoderm and neural crest, each of which generates particular components of the arches, and whose development must be co-ordinated to generate the functional adult oro-pharyngeal apparatus. In the past most studies have emphasized the role played by the neural crest, which generates the skeletal elements of the arches, in directing pharyngeal arch development. However, it is now apparent that the pharyngeal endoderm plays an important role in directing arch development. Here we discuss the role of the pharyngeal endoderm in organizing the development of the pharyngeal arches, and the mechanisms that act to pattern the endoderm itself and those which direct its morphogenesis. Finally, we discuss the importance of modification to the pharyngeal endoderm during vertebrate evolution. In particular, we focus on the emergence of the parathyroid gland, which we have recently shown to be the result of the internalization of the gills.

PMID 16313389


Development of pharyngeal arch arteries in early mouse embryo

J Anat. 2002 Jul;201(1):15-29.

Hiruma T, Nakajima Y, Nakamura H. Source Department of Anatomy, Saitama Medical School, Iruma-gun, Japan.


The formation and transformation of the pharyngeal arch arteries in the mouse embryo, from 8.5 to 13 days of gestation (DG), was observed using scanning electron microscopy of vascular casts and graphic reconstruction of 1-microm serial epoxy-resin sections. Late in 8.5-9DG (12 somites), the paired ventral aortae were connected to the dorsal aortae via a loop anterior to the foregut which we call the 'primitive aortic arch', as in the chick embryo. The primitive aortic arch extended cranio-caudally to be transformed into the primitive internal carotid artery, which in turn gave rise to the primitive maxillary artery and the arteries supplying the brain. The second pharyngeal arch artery (PAA) appeared late in 9-9.5DG (16-17 somites), and the ventral aorta bent dorsolaterally to form the first PAA anterior to the first pharyngeal pouch by early in 9.5-10DG (21-23 somites). The third PAA appeared early in 9.5-10DG (21-23 somites), the fourth late in 9.5-10DG (27-29 somites), and the sixth at 10DG (31-34 somites). By 10.5DG (35-39 somites), the first and second PAAs had been transformed into other arteries, and the third, fourth and sixth PAAs had developed well, though the PAA system still exhibited bilateral symmetry. By 13DG, the right sixth PAA had disappeared, and the remaining PAAs formed an aortic-arch system that was almost of the adult type.

PMID 12171473

Mandible - Temporomandibular Joint Development

Tissue interaction is required for glenoid fossa development during temporomandibular joint formation

Dev Dyn. 2011 Nov;240(11):2466-73. doi: 10.1002/dvdy.22748. Epub 2011 Sep 26.

Wang Y, Liu C, Rohr J, Liu H, He F, Yu J, Sun C, Li L, Gu S, Chen Y. Source Department of Operative Dentistry and Endodontics, College of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, P R China.


The mammalian temporomandibular joint (TMJ) develops from two distinct mesenchymal condensations that grow toward each other and ossify through different mechanisms, with the glenoid fossa undergoing intramembranous ossification while the condyle being endochondral in origin. In this study, we used various genetically modified mouse models to investigate tissue interaction between the condyle and glenoid fossa during TMJ formation in mice. We report that either absence or dislocation of the condyle results in an arrested glenoid fossa development. In both cases, glenoid fossa development was initiated, but failed to sustain, and became regressed subsequently. However, condyle development appears to be independent upon the presence of the forming glenoid fossa. In addition, we show that substitution of condyle by Meckel's cartilage is able to sustain glenoid fossa development. These observations suggest that proper signals from the developing condyle or Meckel's cartilage are required to sustain the glenoid fossa development. Copyright © 2011 Wiley-Liss, Inc.

  • temporomandibular joint (TMJ) is a unique synovial joint that is essential for movement and function of the jaw in mammals.
  • fibrous capsule that encloses the mandibular condyle, the glenoid fossa of the temporal bone, and an articulating disc separating the two articular facets lined with fibrocartilage instead of hyaline cartilage (Sperber, 2001)
  • glenoid fossa forms a deep concavity in the temporal bone, receiving the mandibular condyle to make the hinge of TMJ function.
  • Associated with the TMJ are also the tendon of the pterygoid muscle and various surrounding ligaments.
  • articular disc forms from the mesenchymal cells located between the condyle and the glenoid fossa (Frommer, 1964).
  • condyle development and differentiation do not rely on the presence of the glenoid fossa.
  • Meckel’s cartilage is considered the primary cartilage, while the condyle is classified as the secondary cartilage (secondary cartilage - rapid differentiation from progenitor cells to hypertrophic chondrocytes and its preosteoblastic characteristics)

PMID 21953591

An assessment of early mandibular growth

Forensic Sci Int. 2012 Apr 10;217(1-3):233.e1-6. doi: 10.1016/j.forsciint.2011.11.014. Epub 2011 Dec 7.

Hutchinson EF, L'Abbé EN, Oettlé AC. Source Department of Anatomy, Section: Physical Anthropology, School of Medicine, Faculty of Health Sciences, University of Pretoria, South Africa.


Quantification of skeletal data has been shown to be an effective and reliable method of demonstrating variation in human growth as well as for monitoring and interpreting growth. In South Africa as well as internationally, few researchers have assessed mandibular growth in late fetal period and early childhood and therefore standards for growth and age determination in these groups are limited. The purpose of this study was to evaluate growth in the mandible from the period of 31 gestational weeks to 36 months postnatal. A total of 74 mandibles were used. Dried mandibles were sourced from the Raymond A. Dart Collection (University of Witwatersrand), and cadaveric remains were obtained from the Universities of Pretoria and the Witwatersrand. The sample was divided into four groups; 31-40 gestational weeks (group 1), 0-11 months (group 2), 12-24 months (group 3), and 25-36 months (group 4). Twenty-one osteological landmarks were digitized using a MicroScribe G2. Ten standard measurements were created and included: the maximum length of mandible, mandibular body length and width, mandibular notch width and depth, mental foramen to inferior border of mandible, mandibular basilar widths bigonial and biantegonial, bigonial width of mental foramen and mental angle. Data were analyzed using PAST statistical software and Morphologika2 v2.5. Statistically significant differences were noted in the linear measurements for all group comparisons except between groups 3 and 4. The mandible morphologically changed from a round, smooth contour anteriorly to adopt a more sharp and narrow adult shape. A progressive increase in the depth and definition of the mandibular arch was also noted. In conclusion, the mandible initially grows to accommodate the developing tongue (up to 11 months), progressive dental eruption and mastication from 12 to 36 months. Mastication is associated with muscle mass development; this would necessitate an increase in the dimensions of the mandibular notch and associated muscle attachment sites. These findings might be valuable in the estimation of age in unidentified individuals and to monitor prenatal growth of the mandible for the early diagnosis of conditions associated with stunted mandibular growth. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

PMID 22154436

Mathematical analysis of mandibular morphogenesis by micro-CT-based mouse and alizarin red S-stained-based human studies during development

Anat Rec (Hoboken). 2012 Feb;295(2):313-27. doi: 10.1002/ar.21535. Epub 2011 Dec 21.

Rafiq AM, Udagawa J, Lundh T, Jahan E, Matsumoto A, Sekine J, Otani H. Source Department of Developmental Biology, Faculty of Medicine, Shimane University, Izumo, Shimane, Japan.


Prenatal development of the mandible is an important factor in its postnatal function. To examine quantitatively normal and abnormal developmental changes of the mandible, we here evaluated morphological changes in mineralizing mandibles by thin-plate spline (TPS) including bending energy (BE) and Procrustes distance (PD), and by Procrustes analyses including warp analysis, regression analysis, and discriminant function analysis. BE and PD were calculated from lateral views of the mandibles of mice or of human fetuses using scanned micro-computed tomography (CT) images or alizarin red S-stained specimens, respectively. BE and PD were compared (1) between different developmental stages, and further, to detect abnormalities in the data sets and to evaluate the deviation from normal development in mouse fetuses, (2) at embryonic day (E) 18.5 between the normal and deformed mandibles, the latter being caused by suturing the jaw at E15.5, (3) at E15.5 and E18.5 between normal and knockout mutant mice of receptor tyrosine kinase-like orphan receptor (Ror) 2. In mice, BE and PD were large during the prenatal period and small after postnatal day 3, suggesting that the mandibular shape changes rapidly during the prenatal and early postnatal periods. In humans, BE of the mandibles peaked at 16-19 weeks of gestation, suggesting the time-dependent change in the mandibular shape. TPS and Procrustes analyses statistically separated the abnormal mandibles of the sutured or Ror2 mutant mouse fetuses from the normal mandible. These results suggest that TPS and Procrustes analyses are useful for assessing the morphogenesis and deformity of the mandible. Copyright © 2011 Wiley Periodicals, Inc.

Human Fetuses

Morphogenesis of the mandible during development.

To analyze the morphogenesis of the mandible in human fetuses, BE and PD were calculated. The rate of BE was higher in 121–152 mm CRL (16–19 weeks of gestation) than in those of the other weeks, whereas the rate of PD did not show any peak (Fig. 3E,F). These changes were approximated by the regression functions [BE = 72 sin (0.0006 CRL – 0.036) + 0.35 sin (0.066 CRL – 3.09) + 0.25 sin (0.13 CRL – 4.7), R2 = 0.98 (Fig. 3E); PD = 4.2 exp {−(CRL – 214/69)2}, R2 = 0.98] (Fig. 3F).

Abbreviations used: ANOVA = Analysis of variance; BE = Bending energy; BW = Body weight; CRL = Crown-rump length; CT = Computed tomography; D = Dimensional; DFA = Discriminant function analysis; E = Embryonic day; M = Mean; MRI = Magnetic resonance imaging; P = Postnatal day; PCR = Polymerase chain reaction; PD = Procrustes distance; RA = Regression analysis; Ror = Receptor tyrosine kinase-like orphan receptor; SD = Standard deviation; TMJ = Temporomandibular joint; TPS = Thin-plate spline.

PMID 22190390

Abnormal mandibular growth and the condylar cartilage

Eur J Orthod. 2009 Feb;31(1):1-11. doi: 10.1093/ejo/cjn117.

Pirttiniemi P, Peltomäki T, Müller L, Luder HU. Source Department of Oral Development and Orthodontics, Institute of Dentistry, University of Oulu, Finland. Abstract Deviations in the growth of the mandibular condyle can affect both the functional occlusion and the aesthetic appearance of the face. The reasons for these growth deviations are numerous and often entail complex sequences of malfunction at the cellular level. The aim of this review is to summarize recent progress in the understanding of pathological alterations occurring during childhood and adolescence that affect the temporomandibular joint (TMJ) and, hence, result in disorders of mandibular growth. Pathological conditions taken into account are subdivided into (1) congenital malformations with associated growth disorders, (2) primary growth disorders, and (3) acquired diseases or trauma with associated growth disorders. Among the congenital malformations, hemifacial microsomia (HFM) appears to be the principal syndrome entailing severe growth disturbances, whereas growth abnormalities occurring in conjunction with other craniofacial dysplasias seem far less prominent than could be anticipated based on their often disfiguring nature. Hemimandibular hyperplasia and elongation undoubtedly constitute the most obscure conditions that are associated with prominent, often unilateral, abnormalities of condylar, and mandibular growth. Finally, disturbances of mandibular growth as a result of juvenile idiopathic arthritis (JIA) and condylar fractures seem to be direct consequences of inflammatory and/or mechanical damage to the condylar cartilage.

PMID 19164410

Temporomandibular joint formation and condyle growth require Indian hedgehog signaling

Dev Dyn. 2007 Feb;236(2):426-34.

Shibukawa Y, Young B, Wu C, Yamada S, Long F, Pacifici M, Koyama E. Source Department of Orthopaedic Surgery, Thomas Jefferson University College of Medicine, Philadelphia, Pennsylvania 19107, USA.


The temporomandibular joint (TMJ) is essential for jaw function, but the mechanisms regulating its development remain poorly understood. Because Indian hedgehog (Ihh) regulates trunk and limb skeletogenesis, we studied its possible roles in TMJ development. In wild-type mouse embryos, Ihh expression was already strong in condylar cartilage by embryonic day (E) 15.5, and expression of Ihh receptors and effector genes (Gli1, Gli2, Gli3, and PTHrP) indicated that Ihh range of action normally reached apical condylar tissue layers, including polymorphic chondroprogenitor layer and articular disc primordia. In Ihh(-/-) embryos, TMJ development was severely compromised. Condylar cartilage growth, polymorphic cell proliferation, and PTHrP expression were all inhibited, and growth plate organization and chondrocyte gene expression patterns were abnormal. These severe defects were partially corrected in double Ihh(-/-)/Gli3(-/-) mutants, signifying that Ihh action is normally modulated and delimited by Gli3 and Gli3(R) in particular. Both single and double mutants, however, failed to form an articular disc primordium, normally appreciable as an independent condensation between condylar apex and neighboring developing temporal bone in wild-type. This failure persisted at later stages, leading to complete absence of a normal functional disc and lubricin-expressing joint cavities. In summary, Ihh is very important for TMJ development, where it appears to regulate growth and elongation events, condylar cartilage phenotype, and chondroprogenitor cell function. Absence of articular disc and joint cavities in single and double mutants points to irreplaceable Ihh roles in formation of those critical TMJ components.

Figure 2. Schematics of embryonic day (E) 15.5 and E18.5 condyles. Progenitor and differentiated cells constituting different condylar portions are indicated and reflect widely accepted nomenclature. Also indicated are the expression patterns of marker genes that are based on data in the present study and shown in Figures that follow.

PMID 17191253

Synovial membrane in the temporomandibular joint--its morphology, function and development

Arch Histol Cytol. 2003 Oct;66(4):289-306.

Nozawa-Inoue K, Amizuka N, Ikeda N, Suzuki A, Kawano Y, Maeda T. Source Division of Oral Anatomy, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.


This paper reviews recent findings of the synovial membrane, in particular the morphology, function and development of synovial lining cells, in the temporomandibular joint (TMJ). Electron microscopic studies have confirmed the synovial membrane in TMJ consists of macrophage-like type A cells and fibroblast-like type B cells identical to those in other systematic joints. The macrophage-like type A cells react with anti-macrophage and macrophage-derived substances including the major histocompatibility class II molecule, and show a drastic increase in their number in the inflamed synovial membrane. In addition, they have the ability to produce substances involved in the progression of TMJ inflammation such as nitric oxide and inducible nitric oxide synthase. Observation of osteopetrotic mice revealed that macrophage-like type A cells in TMJ are derived from monocyte lineage. Immunocytochemistry for 25kDa heat shock protein was able to depict the entire shape of fibroblast-like type B cells including their unique processes. The expression of an estrogen receptor alpha-immunoreaction in the fibroblast-like type B cells may explain the etiology of temporomandibular disorders at a higher frequency in females than in males, suggesting that TMJ is a target tissue for estrogen. Furthermore, fibroblast-like type B cells are equipped with a basement membrane to serve as an adhesion molecule for the fibroblast-like type B cells to keep their epithelial arrangement. A clear understanding of the morphology of the intact synovial membrane will serve to clarify the etiology and development of temporomandibular disorders.

PMID 14692685

Crit Rev Oral Biol Med. 1999;10(4):504-18. Craniofacial pain and motor function: pathogenesis, clinical correlates, and implications. Stohler CS. Source Department of Biologic and Materials Sciences, and Center for Human Growth and Development, The University of Michigan, Ann Arbor 48109-1078, USA. Abstract Many structural, behavioral, and pharmacological interventions imply that favorable treatment effects in musculoskeletal pain states are mediated through the correction of muscle function. The common theme of these interventions is captured in the popular idea that structural or psychological factors cause muscle hyperactivity, muscle overwork, muscle fatigue, and ultimately pain. Although symptoms and signs of motor dysfunction can sometimes be explained by changes in structure, there is strong evidence that they can also be caused by pain. This new understanding has resulted in a better appreciation of the pathogenesis of symptoms and signs of the musculoskeletal pain conditions, including the sequence of events that leads to the development of motor dysfunction. With the improved understanding of the relationship between pain and motor function, including the inappropriateness of many clinical assumptions, a new literature emerges that opens the door to exciting therapeutic opportunities. Novel treatments are expected to have a profound impact on the care of musculoskeletal pain and its effect on motor function in the not-too-distant future. PMID 10634586

Mandibular growth rates in human fetal development

Arch Oral Biol. 1995 Feb;40(2):119-25.

Bareggi R, Sandrucci MA, Baldini G, Grill V, Zweyer M, Narducci P. Source Department of Human Morphology, University of Trieste, Italy.


A morphometric analysis of changing proportions in the developing mandible was undertaken in 18 human embryos and fetuses of both sexes (developmental age from 8 to 14 weeks, crown-rump length, CRL, from 34 to 110 mm), previously cleared and stained with a specific method for bone (alizarin red S). Reference points were located on the mandible, i.e. condylar process (Pcl), coronoid process (Pco), gnathion (GN), gonion (GO), superior symphyseal point (SSP), for measuring linear dimensions, i.e. Pcl-GN, Pcl-Pco, Pco-GN, GO-GN, SSP-GN. The gonial (Pcl-GO-GN) and the (Pcl-GN-Pcl) angles were also measured. All linear dimensions were correlated with the CRL by bivariate allometry (1n y = 1n a+b 1n x): they all grew with positive allometry, except GO-GN with isometry. The mandibular ramus grew relatively faster than the body, both in length and height, and the greatest growth rate was found for ramus height. The relation between mandibular shape and the craniofacial structures was investigated using scale drawings obtained from photographs of fetal skulls in lateral view. In the youngest fetuses the mandible was prognathic, then became retrognathic. During the period investigated the zygomatic process and squama of the temporal bone were in a lower and more inclined position in relation to the transverse plane passing through the zygomatic arch than in the newborn and adult. This study identifies parameters fitting changing trends in height, length and shape of the human mandible during the prenatal period (8-14 weeks); moreover, it emphasizes that the mandibular growth patterns differ significantly from those of successive development periods. PMID 7794126