and Head Neck Development
I.
II.
III.
Review
a. critical time for craniofacial development is wk 3-4 (same as gastrulation)
b. Neural crest cells bones of face & anterior skull
c. Mesoderm posterior bones & base of skull
d. Lateral Plate Mesoderm laryngeal cartilage
Somitomeres
a. Week 3: paraxial mesoderm differentiates into somitomeres
i. differentiate in cranial to caudal fashion
ii. 7 somitomeres
iii. key in segmenting brain into fore- mid- hind- brain segments by inducing
neural tube (via chemogradients)
b. somitomere = incompletely differentiated (in head)
c. somite = completely differentiated (found in lower body)
d. somitomeres form all voluntary muscles in head/neck; but scaffold (patterning)
is by connective tissue elements
Neural Crest Cells and Pharyngeal Arches
a. NCCs: migrate from neural folds in cranial-to-caudal sequence to somitomeres
pharyngeal arches (brachial arches)
i. directed by HOX genes populate specific regions of head/neck
ii. MSX-2 genes: specific suicide signal to NCCs along rhombomeres 3 &
5
1. produces gaps (brachial grooves)
2. ensures non-mixing between populations of NCCs
iii. Rhombomere: subdivision of hindbrain (segment of neural tube)
1. each rhombomere has its own HOX code
2. NCCs in each rhombomere migrate to brachial arches with
compatible HOX code specific link between face & brain
development
iv. NCCs provide link between development of face & brain; key BUT also
very sensitive to teratogens
b. Pharyngeal Arches (Brachial Arches)
i. General:
1. develop during 4th week of gestation
2. lateral swellings on either side of head; result from local
proliferation of NCC
3. give rise to specific cartilages and bones
4. pharyngeal groovesexternal delineations between brachial
arches; ectoderm covered
5. pharyngeal pouchesinternal deliniation between brachial arches;
endoderm lined
6. closing membranesectoderm/endoderm contact points ensuring
non-mixing between brachial arches
ii. Aortic Arch Arteries
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1. blood vessel development follows path of least resistance (thru
mesenchyme) => many run through brachial arches during early
embryogenesis
iii. Cranial Nerveseach is associated with a specific pharyngeal arch &
innervates all its muscles, etc
iv. Muscleseach pharyngeal arch differentiates into a specific set of
muscles which are innervated by the CN in that arch
Arch
Artery
Nerve
Skeletal Elements
(NCCs) Maxilla,
mandible, zygomatic
portions of temporal,
Muscles
mm. of mastication (temporalis, masseter,
pterygoids) myelohyoid, ant. belly of
digastric, tensor tympani, & veli palatini
1
Maxillary
V(V2 & V3
only)
2
Stapedial
(practically
degenerates)
VII
(NCCs) Stapes, styloid
process, part of hyoid
muscles of facial expression, post. belly
of digastric, stylohyoid, stapedius
3
Carotid
IX
(NCCs) Part of hyoid
Stylopharyngeus
4
Right:
subclavian,
Left: arch of
the aorta
X (superior
laryngeal br)
(LPM) Laryngeal
cartilages
Cricothyroid, levator veli palatine,
pharynx constrictors
5
-
-
-
-
6
Pulmonary
X (recurrent
laryngeal br)
(LPM) Laryngeal
cartilages
Intrinsic larynx mm.
IV.
Pharyngeal Pouches & Grooves
a. Pharyngeal Pouches (Glands)
i. First Pharyngeal Pouch
1. forms the auditory tube (narrow proximal part) & tympanic
cavity (distal sac-like structure)
2. tympanic membraneforms from lining of tympanic cav.
3. later comes into contact with epithelial lining of 1st pharyngeal
cleft (future EAM)
ii. Second Pharyngeal Pouch
1. proliferates to form palatine tonsil
iii. Third Pharyngeal Pouch
1. forms thymus and inferior parathyroid glands
2. thymus descends during development, pulling superior/ inferior
parathyroid glands with it
iv. Fourth Pharyngeal Pouch
1. forms superior parathyroid glands
2. attach to dorsal surface of thyroid
v. Fifth Pharyngeal Pouch
1. forms ultimobrachial bodyregulates Ca2+ in body & is
embedded in thyroid
b. Pharyngeal Grooves (Clefts)
i. four recognizable clefts; all but one disappear during development
2
V.
VI.
VII.
ii. 1st pharyngeal cleft external auditory meatus (EAM) & part of
tympanic membrane
iii. 2nd pharangeal arch mesenchyme proliferates overlapping arch that
covers 2-4th pharangeal clefts smooth neck
iv. cervical sinustemporary cavity formed during development; closes later
during development
Tongue Development
a. Essentially a group of muscles covered by mucosa
b. Mucosa
i. Endoderm derived; from 1-4th pharyngeal arches
ii. Sensory Innervation:
1. anterior 2/3mostly 1st brachial arch CN V
2. Posterior 1/33rd & 4th pharyngeal arches CN IX & X
iii. Special Sensory (Taste): CNs VII (ant 2/3), IX, & X (post. 1/3)
c. Frenulumband of tissue underlying tongue that anchors it to floor of mouth;
extensively degenerates during development
d. Terminal sulcussulcus separating anterior part of tongue from posterior
e. Foramen Cecummidpoint of sulcus; position of thyroid outgrowth
Thyroid Gland Development
a. Arises from epithelial proliferation (endoderm) in floor of mouth on midline @
foramen cecum
b. Descends along vertical path to above laryngeal cartilages
c. Remains connected to tongue via thyroglossal duct (a narrow canal)
Facial Development
a. Frontonasal Prominences
i. Frontonasal prominencemesenchyme surrounding forebrain
ii. Nasal Placodelocal thickening of surface ectoderm; develops into
medial/lateral nasal prominences (develop into nose)
iii. Medial nasal prominence (MNP)
iv. Lateral Nasal Prominence (LNP)
b. Stomadeumpromitive oral cavity located below frontonasal prom.
c. 1st Arch Pharayngeal prominences
i. Maxillary Prominence(MxP) dorsal
ii. Madibular Prominenceventral; forms mandible
d. Steps in Development
i. Nasal Placode and 1st pharyngeal arch divide into MNP/MLP &
MxP/mandibular prominences respectively
ii. MxP merge with MNP, pushing them closer to the midline
iii. MNPs fuse, forming midline of nose and upper lip (philtrum), and
primary palate (part of palate carrying front four teeth)
iv. Nasolacrimal groove (deep furrow) divides MxP & LNP, canalized to
form nasolacrimal duct (and lacrimal sac)
v. MxP & LNP fuse with eachother
vi. MxP enlarge to form cheeks and maxillae; LNP enlarge to form sides of
nose
e. Secondary Palate
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VIII.
IX.
i. Palatine Shelvesgrow out from MxP during 6th week; begin directed
downward on either side of tongue
ii. Attain horizontal position and fuse with each other once tongue drops
secondary palate
iii. Incisive foramenmidline landmark between primary/secondary palate
fusion point
iv. Soft palatemucosa posterior to hard palate
Ear Development
a. External Ear (3 parts)
i. External Acoustic Meatusder. From 1st pharyngeal cleft
ii. Tympanic Membrane (eardrum)3 layers: ectodermal epithelial lining
from EAM, endodermal epithelial lining of tympanic cavity, &
intermediate layer of connective tissue
iii. Auricle (external ear)dev from 6 mesenchymal proliferations
(auricular hillocks) of 1st & 2nd pharyngeal arches
1. fuse to form definitive auricle; pushed upward, backwards, and
rotated 90 degrees to final position
2. problems w/ auricular development often indicated 1st / 2nd
pharyngeal arch problems/defects
b. Middle Ear (2 parts)
i. Tympanic cavity & auditory tubefrom 1st pharyngeal pouch
ii. Ossicles(malleus, incus, & stapes) embedded in mesenchyme during
most of development; in 8th month it degenerates & endoderm envelops
them & connects them to wall of cavity
1. malleus1st pharyngeal arch (tensor tympanin = accompanying
m. inn by CN V)
2. incus1st pharyngeal arch
3. stapes2nd pharyngeal arch (stapedius m = accompanying m. inn
by CN VII)
c. Inner Ear (2 parts):
i. Begins as otic placodes invaginate to form otic vesicles
ii. Ventral (saccule & cochlear duct)
1. Cochlear Ductinitiates as outgrowth of saccule; penetrates surr.
mesenchyme in spiral fashion
2. scala vestibule & scala tympani2 compartments surrounding
cochlear duct
3. Responsible for hearing via CN VIII
iii. Dorsal (utricle/semicircular canals & endolymphatic duct)
1. Utricle forms 3 flattend outpocketings loses central core &
semicircular canals form
2. responsible for balance via CN VIII
d. many craniofacial syndromes are associated w/ ear/hearing deficiencies; if pt.
presents w/ ear malformations know what to look for!
Eye Development
a. Process
4
X.
i. Evagination of forebrain optic vesicles; connect to brain via optic
stalks
ii. Optic vesicles induce surface ectoderm to become columnar lens
placode
iii. Invagination of optic vesicles bilayered optic cup
iv. Blood supplied to eye via hyaloid artery (feeds growing lens; degenerates
later in dev) in groove (known as choroid fissure)
v. Choroid fissure closes optic stalk becomes optic nerve
b. Layers
i. Sclera = continuous with dura mater; tough connective tissue
1. cornea = transparent; anterior 1/6 of eye; continuous w/ sc.
2. ciliary mm = control size of lens; arise from mesenchyme
3. papillary mm = control light entry into eye; arise from
mesenchyme surrounding eye
ii. Iridopupillary Layerchoroid layer
iii. Retina/Iris
1. retinadirect derivative of optic cup (3 layers of cells)
2. Irisforms via an outgrowth of the anterior body
Clinical Correlations
a. Treacher Collins Syndromzygomatic Hypoplasia (severe) due to 1st arch
deficiencies (maxillary and mandibular)
b. Robin Sequencemandibular hypoplaxia, cleft palate, posteriorly placed tongue
(less severe than treacher Collins) due to 1st arch deficiency
c. Hemifacial Microsomiahypoplasia of zygomatic, temporal and maxilla bones,
small/missing external ear, usually asymmetrical; due to 1st arch (and 2nd
sometimes) deficiency
d. Lateral cervical cystsalong anterior border of sternocleidomastoid muscle;
result from incomplete closure of cervical sinus
e. Ankyloglossia(tongue tied) tongue not freed from floor of mouth via
degeneration of frenulum frenulum extends to tip of tongue
f. Thyroglossal cysts (or fistulas)anywhere along thyroid migratory path on
midline; caused by incomplete closure of duct
g. Lingual Thyroidthyroid fails to descend; instead develops atop tongue
h. Unilateral/bilateral cleft lipMxP on 1/both sides fail to fuse with MNP
(sometimes associated with lack of primary and/or secondary palate fusion
i. Median cleft liprare anomaly; incomplete merging of the 2 MNP on midline;
often associated with mental retardation & loss of midline structs
j. Oblique facial cleftsfailure of MxP to fuse with LNP; nasolacrimal duct is
usually exposed to surface
* Cleft lip=multifactorial in origin; incidence 1:1000, > in ; teratogen causes
k. Cleft Palateno fusion between palatine shelves; multifactoral; 1:2500, > in
(possibly b/c secondary palate fuses ~ 1wk after )
l. Clefting of Soft Palate(cleft Uvula) incidence 1:100; non-pathological
m. Colobomaincomplete iris caused by nonclosure of choroid fissure
n. Synopthalmafusion of eyes (partial or complete); ALWAYS accompanied by
other facial/brain midline defects
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o. Holoprosencephalycontinuum of midline malformations => from early loss of
midline progenitor cell populations (can be teratogen induced)
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