Again refer to the handouts for pretty pictures, diagrams, etc.
Summary of Nasal Formation (Recap)
Face develops from the medial nasal processes (MNP), lateral nasal processes (LNP), maxillary processes, mandibular processes, and frontonasal process. The nasal processes form the ala and the bridge of the nose. The bulb and tip of the nose come from the MNPs. The MNPs fuse with the maxillary processes to form a complete upper lip. Behind this the ethmoid bone develops from mesenchyme.
Formation of the Choanae
Early on, when the processes are open, the nasal and oral cavities communicated. This then closes off to separate these cavities and separate the nose into right and left cavities. The nasal cavity surrounds the nasal placode and all structures derived from the placode then go on to differentiate into the respiratory epithelium, olfactory epithelium, etc. The intermaxillary segment extends posteriorly to form part of the primary palate as well as some of the anterior dentition. As the nasal cavity forms, the oro-nasal membrane (buccopharyngeal membrane) must thin out and eventually rupture to allow a posterior communication with the oropharynx. This newly formed holes are the choanae. These holes are initially much further forward but as the secondary palate develops, these holes take a much more posterior position.
If the oronasal membrane persists, then CHOANAL ATRESIA results. This can be bilateral or unilateral as well as soft tissue or even bone. Several mechanisms could explain this. The FNP could come down and fuse with the palate. There could be tissue migration into the area such as neural crest tissue, or because crest cells did not migrate into the area thus causing soft tissue invaginations that narrow the area. The "key of the skull" is the sphenoid bone as it is centrally located and a lot of other structure come off this bone. The ethmoid bone which comes off the sphenoid (and is neural
crest derived) is thought to be a strut that helps to keep midface height during development of the face. Any abnormality of the ethmoid bone may then alter the development of the midface as well as the size of the choanae. The horizontal component of the ethmoid, the CRIBRIFORM PLATE, and the vertical component, the PERPENDICULAR PLATE, may also contribute to atresia if there are developmental problems by altering the final dimensions of the nose.
90% OF CHOANAL ATRESIAS ARE SOFT TISSUE.
**Be sure to remember that Dr Toohill considers the palatine bone to be part of the nasal septum along with the dorsal cartilage, maxilla, perpendicular ethmoid plate, and vomer. He also feels there are only 2 turbinates even tho there are usually 3. Our anatomist friend states that there are 2 turbinates endogenous to the ethmoid bone (superior and middle) whereas the lower one is an autogenous bone that associates itself with the ethmoid.
Human Facial Form Achieved by Week 8
Muscle primordia from arch II --> arch I: muscle from arch II
covers the structures formed by arch I
Elongation and Hypertrophy of arch I (this arch contributes most to the head and neck esp the maxillary and mandibular aspects)
Ears move superio-dorsally
Eyes move toward midline
Facial Anomalies
Many facial anomalies are associated with malformations of the
brain esp prosencephaly such as cyclopia w/ or w/o a proboscis, ethmocephaly (hypotelorism and a proboscis), telocephaly with one nostril and hypotelorism. Can also have prosencephaly with a normal face. Arhinoncephaly is where there is no nasal structures such as olfactory apparatus and can have facial problems with this such as facial clefting or intermaxillary segment problems.
Median Cleft Lip: If hypotelorism is present (have to measure this on Xray), can expect prosencephaly. The MNP never fuse together in median cleft lip. No known cause. Isolated median cleft lip is very rare: 1/600 out of all cleft lips.
Unilateral or Bilateral Cleft Lip: It is more common--this is where the LNPs and maxillary processes do not fuse. Can be unilateral or bilateral. The degree of clefting can be variable. Can include jaw and palate. Sexual dimorphism: Cleft lip more common in males and cleft palate more common in females. The palate closes later in males to explain this.
Oblique Facial Cleft: If the facial cleft is oblique, this means the problem occurred in the area where the maxillary process fused with the LNP. If the cleft extends straight out from the mouth, it was a problem with the fusion of the maxillary and mandibular processes. As a general rule, these kinds of clefts occur where there are merging of various processes. Lateral facial clefts can occur clear back to the ear. These clefts can occur in combination with cleft lip/palate.
First Arch Syndrome (Treacher Collins):
Mandibulofacial Dysostosis or Franceschetti-Zwahlen-Klein Syndrome
1) Autosomal dominant or intrauterine abuse
2) Antimongoloid palpebral fissures with notched lower lids
3) Malformation of ossicles (stapes usually normal)
4) Auricular deformity, EAC atresia
5) Conductive hearing loss
6) Preauricular fistulas
7) Mandibular hypoplasia and malar hypoplasia
8) "Fish Mouth"
9) Normal IQ
10)Usually bilateral involvement
11)May have cleft lip and palate
12)Arrest occurs at 6-8 weeks of development
Mandibular Hypoplasia (Pierre Robin): (Cleft Palate, Micrognathia, and Glossoptosis) A first arch problem also.
1) Autosomal Dominant with variable penetrance; possibly not
hereditary but due to intrauterine insult
2) Occurs 1:30000 to 1:50000 live births
3) Glossoptosis
4) Micrognathia
5) Cleft palate (50% of cases)-- has a classic U-shaped
appearance. This may be due to glossoptosis causing
pressure on the palate and preventing closure of the
12)Premature closure of the cranial suture lines can lead to
mental retardation
CHARGE ASSOCIATION:
C: Colobomata
H: Heart defects
A: Choanal Atresia
R: Mental Retardation
G: Genital hypoplasia- generally in males
E: Ear anomalies
The common denominator for all these problems/syndromes may lie with the neural crest cell population--either due to faulty migration or more likely due to insufficient crest tissue. The CHARGE syndrome's heart defects may indeed be due to these neural crest cell problems as well as choanal atresia as was already mentioned.
Drug Effects
Accutane (for acne): fish-like scales on skin and ear
anomalies
DEVELOPMENT OF THE PALATE
Primordia
1) MNP (Primary palate): the MNPs fuse together to form the
intermaxillary segment and this segment has a palatal
component. This forms the primary palate.
2) Maxillary Processes (Secondary Palate)
The MPs plus the palatine bone forms the secondary palate.
This is neural crest derived bone.
a) Lateral palatine processes: These first project inferiorly and then medially. These will eventually fuse
with the perpendicular plate of the ethmoid to form the secondary palate.
Formation of the Hard and Soft Palates
Incisive Foramen marks the point of fusion
1) shelf force: The palatal shelves (during the time that the tongue is getting out of the way-see below) begin to
swell because they are full of "glyco-conjugates" and
swell with water. This forces a rearrangement of cells
and extracellular matrix. This process "drives" palatal closure. This "force" is a directed force so that closure
occurs in the correct manner and direction. Growth factors may be involved here. Cleft palate often associated with cleft lip.
Hard Palate ossifies intramembranously: this occurs without
a cartilage model which would interfere with closure.
Soft Palate-- caudal proliferation of secondary palate
1) uvula: Can be bifid uvula w/ or w/o submucous cleft palate
Role of Tongue in Palate Formation
The tongue is very important in palatal formation. The tongue can get in the way of the palatal processes and prevent fusion. The tongue normally gets out of the way of the palate by extending forward and dropping down inferiorly thereby increasing the distance away from the palate. The face is also getting longer and the vertical height is increasing at this time.
CLEFT PALATE: in complete fusion or failure of fusion
Etiology: Multifactorial(Genomic and Environmental Influences)
: 1/700 births show cleft palate and/or lip
: 13% of all anomalies involve these structures
: If isolated cleft lip or palate, probably multifactorial
: More likely genetic if associated with a full-blown syndrome.
: There are 153 syndromes that are associated with cleft lip and/or palate
Please see handout for the table showing all the influences, frequencies, and risks for cleft palate/lip.
Morphogenic Factors Leading to Cleft Palate
1)Abnormal Tongue Development (See above)
2)Cyst formation from epithelial pearls/rests along the palatal closure line can cause secondary ruptures of the palate because of incomplete bone formation.
3)Impedement of shelf force
DEVELOPMENTAL HISTORY OF THE PHARYNGEAL ENDODERM
Salivary Glands
1)Primordia of the Major Salivary Glands--(parotid, submandibular, and sublingual) possibly derived from the pharyngeal endoderm and oral ectoderm. This is controversial as to whether it is endoderm and/or ectoderm.
2)Primordia of the Minor Salivary Glands--derived from oral ectoderm
3)Morphogenesis of Exocrine Glands
All glands begin this way--if the connection to the surface ectoderm remains, then the gland is exocrine. If not, then it is endocrine.
Solid Cords of cells that bud down into the mesenchyme. Tissue interaction again drives this and the mesenchyme determines the branch points of the ducts.=>
Canalized centrally=>
Secretory portions and ducts are then formed.
4)Abnormal Development:
Ranula
Absence of the glands
These glands are an important source of IgA
THYROID GLAND
One of the earliest structures to develop in the pharynx. It develops as a thickening in the floor of the pharynx between the 1st and 2nd arches. It "comes down from" the area of the foramen cecum on the tongue.
Morphogenesis of Endocrine Glands
Solid cords=>loss of epithelial connection=>
secretory portion
Develops ventral to the heart and migrates to a place ventral to the laryngotracheal diverticulum.
Origin of the Thyroid Diverticulum- Foramen Cecum
1) Thyroglossal Duct: Normally this duct, that connects the foramen cecum to the thyroid gland, disappears; however, this can persist.
Adult Position: due to differential growth of the embryo, not due to a "descent" of the thyroid
Abnormal Development
Agenesis: causes true cretinism
: thyroid gland is very important to development of the CNS
Persistent Thyroglossal Duct
-cysts
-fistula
Both can be associated with a pyramidal thyroid lobe.
Aberrant Thyroid Tissue: can occur anywhere in the path of the descending thyroid, usually below the hyoid bone but can be above.
PHARYNGEAL POUCHES
1) First Pouch- remains connected to the pharynx
a) forms components of the ear
Pinna: 6 auricular hillocks
External meatus: formed from the first cleft
TM: the first closing plate remains to form this
Middle ear cavity and ossicles develop from the 1st and 2nd arch
2) Second Pouch: convoluted crypts filled with B-lymphocytes
: palatine tonsil
3) Third Pouch: dorsal and ventral wings
a) Dorsal wing => inferior parathyroids
solid cords => gland parenchyma
attaches to "migrating" thyroid or to thymus
b) Ventral wing => thymus
solid cords => parenchyma
infiltrated with lymphocytes/T-cell precursors
midline fusion and ventral migration
4) Fourth Pouch: has dorsal and ventral wings and receives the 5th pouch
: Dorsal wing becomes the superior parathyroids
: Ventral wing
5) Ultimobranchial body: opens into the 4th pouch
: infiltrated with neural crest cells
which become parafollicular "C" cells (from the 5th pouch).
They develop as a cascade of processes (see the flow sheet).
The ear starts out as a developmental field in the embryo. The first inducer of the ear (at 20 days) is the axial mesoderm-- it induces some of the ectoderm on the side of the embryo to become the "ear field". Otic placode cells will form 60-70% of the neurons for the ear; also, neural crest cells come into this area and "activate" the placode. This is the 2nd inducer for the ear. This forms a small pit surrounded by big surface ectodermal cells--this then becomes the otic vesicle. By 28 days, this fuses off and sinks below the surface and cannot be seen any longer. This otic vesicle (otocyst)then begins to reshape itself. As it is doing that, it becomes very close to the rhombencephlon and an inductive interaction occurs here with cells streaming away from it to form the spiral ganglia and the vestibular ganglia (both come from the otic placode). The neural crest cells that surround these other cells are glial cells.
There is a "periotic capsule" that forms around these cells from which the skeletal elements derive that surround the cochlea.
Once the vesicle goes beneath the surface, it differentiates into an upper vestibular and lower cochlear portion. The semicircular ducts form from the upper portion. The endolymphatic duct develops as a small bump or endolymphatic diverticulum. The utricle develops from the midportion of the vestibular part of the vesicle. The lower portion forms the cochlea, cochlear duct, and the saccule develops from this midportion of this.
Through cell culture experiments, each cell population knows what it is to become or is "preprogrammed" (regional specification). Molecular probe experiments have also helped in this regard. Have you guys noticed that this fellow goes on about stuff that really doesn't seem to have any relevance to what we're doing??
The osseous labyrinth comes from the mesenchyme that condenses around the otocyst (as was alluded to above).
Once the semicircular canals and ampullae have formed, the neurosensory areas encourage nerves to grow into these areas and provide the connections to the CNS.
The stapes footplate forms as part of the Otic Placode whereas the superstructure comes from the arches.
The Middle Ear
See handout-- it forms from the 1st and 2nd arches. The bones are surrounded by the 1st arch cavity. The pouch epithelium (cuboidal) lines the middle ear and mastoid. The infant is not born with a mastoid process--this forms after birth and slowly pneumatizes and retains its lining. Sinuses are formed the same way. Dr. Haberkamp states that the malleal folds that are formed should be studied because they can be very important in the way that cholesteatomas spread through the middle ear.
The External Ear
Hillocks were covered previously.
Congenital Hearing Loss
There is a strong genetic basis for this. Rubella also is known for its affinity for hearing--now rare due to all the vaccinations. Erythroblastosis fetalis also is rarely seen due to the attention paid to blood types at birth and Rhogam.