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Craniofacial embryology and growth
Embryology
Week 1
 Fertilization
 Cleavage
o Mitotic division
o Morula (32 cell) – day 3-4
o Blastocyst as develops fluid filled cavity – day 5
 Implantation
Week 2
 Forms 2 layers
o Epiblast (primary ectoderm)
o Hypoblast (primary endoderm)
Week 3
 Gastrulation
o Under control of homeobox gene
o Cells from epiblast layer develop pseudopodia and migrate between epiblast
and hypoblast in the midline forming the primitive streak. (mesoderm)
o The migrating cells that ingress through the primitive node migrate caudally
to form the prechordal plate and notochordal process
1. Notochordal process induces development of vertebral bodies
o Those that ingress through the primitive groove form the mesoderm lying on
either side of the midline – condensing into rod-like structures
1. paraxial mesoderm – forms axial skeleton, voluntary muscle, dermis
2. intermediate mesoderm – urinary system
3. lateral plate mesoderm
 ventral layer – mesothelial covering for organs
 dorsal area – body lining, majority of dermis, tendons
o The hypoblast is replaced by the migrating epiblast = this forms the definitive
endoderm
o Thus the trilaminar germ disc are all derived from the epiblast
 Paraxial mesoderm
o Cells form rounded whorl like structures – somitomeres
o Over next few days, become organized into discrete blocks – somites
o The first seven pairs of somitomeres do not go on to form somites
o The first 4 pairs of somites contribute to development of:
1. basi-occipital bone
2. tongue muscles
Origins of craniofacial muscles:
Mesodermal
Muscles
Innervation
Origin
Somitomeres 1, 2
Superior, medial and ventral recti
CN III
Somitomere 3
Somitomere 4
Somitomere 5
Somitomere 6
Somitomere 7
Somites 1, 2
Somites 2-5
Superior oblique
Muscles of mastication
Lateral rectus
2nd arch muscles
Stylopharyngeus
Intrinsic laryngeals
Tongue muscles
CN IV
CN V
CN VI
CN VII
CN IX
CN X
CN XII
Week 4
 Somites separates into 3 components
1. sclerotome
 develops into vertebrae
 abnormal development leads to spina bifida
2. myotome
3. dermatome
 Neurulation
o Folding of the neural plate into neural tube
o PAX6, Sonic Hedge-Hog (SHH), and FGF signaling are involved with
neurulation
o Neural crest cells from the lateral margins of the folding neural tube
detach and migrate
o timing and extent of neural cell migration and differentiation is dependent
on a complex patterning of inductive homeobox gene (HOX, MSX)
signaling between the neural crest and adjacent neural tube, lateral plate
mesoderm, and epidermis
o All of the skeletal and connective tissue components of the face (except
enamel) – dentin, cartilage, bone dermis, smooth muscle, subcutaneous fat
and connective tissue surrounding blood vessels, glands, muscle are neural
crest derived
o Skull bone superior to the sella turcica are neural crest derived
o Problems in neurulation may result in midline neurologic and
craniofacial malformations such as holoprosencephaly (single cavity
forebrain), cycloplegias, neural tube defects, and midline orofacial
clefts
o Deficiencies in neural crest tissue migration or proliferation produces
a varied and extensive group of craniofacial malformations referred
to as neurocristopathies, which include von Recklingshausen
neurofibromatosis, hemifacial microsomia, orofacial clefts, and
DiGeorge and Treacher Collin syndromes
Facial development
 A series of inductive events between the prosencephalon, mesencephalon, and
rhombencephalon and the neural crest tissue that migrates into the craniofacial
complex and pharyngeal arch apparatus helps to form the five facial prominences (the
frontonasal and the bilateral maxillary and mandibular prominences)

Groove between lateral nasal process and median nasal process forms nasolacrimal
duct

In the region rostral to the somites, neural crest emigrate as 3 distinct populations (J
Anatomy Nov 2005)
1. trigeminal crest – migrates to the frontonasal and first branchial arch
a. contributes to the neural crest component of trigeminal ganglion
2. hyoid crest – migrates to the second branchial arch
3. vagal crest – migrates to the third and subsequent arches and also extensively
within the trunk

The two migrating populations (trigeminal and hyoid) do not mix – suggesting the
deployment of an inhibiting mechanism
The trigeminal neural crest cells also maintain separation from the adjacent cranial
mesenchyme cells.
The crest cells migrate immediately under the surface ectoderm, forming a pathway
between ectoderm and mesodermal mesenchyme

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Craniofacial growth
Overview of facial growth
 Maxilla lengthens in a posterior direction at the maxillary tuberosity
 Posterior lengthening rotates the maxilla anteriorly and inferiorly
 Simultaneously posterior lengthening of the condyle and ramus displaces the
mandible anteriorly
Growth of the middle cranial fossa secondarily displaces the maxilla and the
mandible forwards.
Theories of craniofacial growth

Herring describes three theories of cranial facial epigenesis.
1. The first theory embraces the notion that the initial form of the skull is genetically
determined, but that when function begins(after birth or hatching), epigenetic
regulation takes over. Emphasis here is on the onset of function as the marker for the
start of epigenetic regulation.
2. The second theory considers cartilage as the pacemaker for skeletal growth. Here,
the form of facial cranial cartilages is genetically dictated, whereas the form of bones
is epigenetically regulated by the cartilage. This theory was forwarded by Scott, who
thought that the cartilage of the cranial base, nasal capsule and Meckel's cartilage act
as pace-makers for the early growth of the facial skeleton.
3. The third theory of skull growth, proposed by Moss, is the functional matrix
hypothesis.
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In Moss' view, overall growth and development of the head is regulated by the
development of its soft, nonskeletal parts, with skull growth being completely
secondary to the prior development and constraints of its enveloping soft tissues.
The hypothesis is rooted in an approach to anatomy in which the head and neck are
conceived as performing a set of functions, such as vision, hearing, or digestion
A functional matrix is the set of all soft tissues, i.e., cells, tissues, organs, and air
volumes that carry out a specific function.
For each soft-tissue matrix, a skeletal unit composed of hard tissues exists, i.e., bone,
cartilage, and dense connective tissue, which protects and supports the matrix
The most fundamental dictum of the hypothesis is succinctly stated by Moss as bones
do not grow, they are grown (within functional matrices).
Cranium
 Vertebral skull is formed from 2 tissues
1. neural crest - Only the trigeminal population contributes to the skull
2. mesoderm
 cranium is made up of
1. neurocranium - which includes the chondrocranium of the skull base and the
membranous bone of the calvarium
2. viscerocranium that forms the membranous bones of the face.
 The various areas of the craniomaxillofacial skeleton grow by very different methods.
 Neurocranium
a. The cranial vault sutures are skeletal joints of the syndesmosis type
b. The sagital, metopic and lambdoid are formed by narrowing of membranous
gaps between bones that are initially widely separate. They overlie areas in
which brain tissue does not lie close to the surface
c. The coronal suture is different and the parietal bone can be seen to overlap the
frontal bone from the outset – this is a flexible/sliding joint.
d. Its base is formed by endochondral ossification and the joints are of the
synchondrosis type. The cartilaginous precursors form around the preexisting cranial nerves and blood vessels. Thus the foramina around the
great vessels occur within the endochondral bones of the skull base
e. Thus endocondral ossification in the cranium exists in the petrous and mastoid
process of temporal bone, occipital, ethmoid, sphenoid and Meckel’s part
of the mandible
 Viscerocranium
a. zygomatic, maxillary, and palatine
i. overlapping or sliding joints where the direction of bone growth tends
to parallel the plane of the suture.
ii. This arrangement provides for adaptive adjustments to pressure in
utero and early infancy.
Growth of cranial vault
 The sutures are growth sites where cells undergo proliferation and differentiation into
osteoblasts.
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The interlocking peg-and-socket arrangement allows osteogenesis to occur mainly at
the bottom of the socket and point of the peg (suture front) for simultaneous jointing
and growth of the bone against the suture.
The sutures produce new bone in response to the expanding neurocranium
The dura contains osteoprogenitor cells which is not present in the periosteum layer.
In very young animals, if skull is excised but dura left behind, the dura has the ability
to regenerate the cranium and its sutures.
Maxilla Growth
Horizontal growth
 Horizontal lengthening of the maxillary arch is produced by remodeling at the
maxillary tuberosity (deposition site) – a major (but not only) growth site
 Deposition occurs in 3 directions – posteriorly, laterally and inferiorly.
 The endosteal surface is resorptive and contributes to the formation of the maxillary
sinus.
Vertical growth
Nasal septum theory
 Maxilla remodels in a posterosuperior manner becoming displaced in an opposite
anteriorinferior direction
 Expansion of cartilage in the nasal septum exerts an anterior and inferior pull at the
septomaxillary ligament.
 This sets up tension in all maxillary sutures – the bones secondarily enlarge at their
sutures in response to the tension created
 Most sutures in the facial complex do not simply grow in perpendicular plane to
suture (as in calvarial sutures) – sutures of maxilla, lacrimal, zygomatic, nasal and
ethmoidal bones also undergo slide
 Zygoma growth mirrors maxilla – malar deposition laterally and posteriorly, rotating
nose anterior-inferiorly
Moss functional matrix
 Soft tissue parts and their growth and functioning orchestrate the remodeling
pattern
Palatal remodeling
 Lining surfaces of the bony walls and floor of the nasal chambers are resorptive.
Produces a lateral and anterior expansion of the nasal chambers and a downward
relocation of the palate
 The oral side of the bony palate is depository,
 The external side of the anterior part of the maxillary arch is resorptive, with bone
being added onto the inside of the arch – this increases arch width, widening the
palate.
Mandibular growth
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Largely membranous ossification but has endochodral component with Meckel’s
cartilage)
Principle growth vectors are posterior and superior
Ramus remodeling is important as it positions the lower arch in occlusion with the
upper
The body principally undergoes anterior-inferior displacement
Ramus growth
 Lingual tuberosity is the anatomic equivalent of maxillary tuberosity – a major
growth site
 Deposition occurs on its posterior facing surface
 Coronoid process grows superiorly and posteriorly
 Soft tissue parts and their growth and functioning orchestrate the remodeling pattern
(Moss functional matrix)
 Single field of surface resorption is present at the inferior edge of the mandible at the
body-ramus junction – this forms the antegonial notch
Condylar growth
 A secondary growth center (once thought to be a pacesetting master center) – it is not
a primary determinant of mandibular growth
 Grows superiorly and posteriorly following the growth of the ramus but not leading it
 Condylar growth is primarily mediated by traction from surrounding soft tissues
(muscles of mastication,tongue)