prenatal craniofacial development

Question 1

Coordination of Face & Brain Development

Answer 1

both develop at overlapping time periods

Question 2

Cranial Neural Crest Cells derivatives

Answer 2

contribute to derivatives of all 3 germ layers in craniofacial development

Question 3

facial morphogenesis complexity? involves what processes?

Answer 3

Morphogenesis of the face is a complex 3D process involving patterning, outgrowth, fusion and molding of tissues

Question 4

head/neck at 22 days size

Answer 4

half the embryo

Question 5

when pharyngeal arches form, how?

how many?

Answer 5

•During 4th week, ventral mesoderm condenses into a series of segmented bilaterally paired, mesenchymal swellings
> ultimately 5 pairs, arising in cranial-caudal order

Question 6

organization of the arches (layers)

Answer 6

Question 7

The Early Facial Prominences

growth directions?

Answer 7

Initially, five prominences (tissue masses) surround the stomodeum:
Øfrontonasal prominence
Øfirst arch (> mandibular process)
Ømaxillary process (delayed appearance)
First (mandibular) arch and maxillary processes are both paired structures
> grow ventro-laterally around the OM

Question 8

oropharyngeal membrane breaks down when?

Answer 8

breaks down during 4th week,

Question 9

Conservation of Facial Morphogenesis

Answer 9

conserved across multiple species; in early stages we look similar to other species

Question 10

Pharyngeal Arch growth driving factor

Answer 10

majority of the growth and morphological change in facial tissue masses is driven by the invading cranial neural crest-derived mesenchyme.

Question 11

pahryngeal clefts and pouches

Answer 11

pouch: inside
cleft: outside

Question 12

what effect does the migrating NCC have on mesoderm

Answer 12

mesoderm derived mesenchyme will restrict as the NCC mesenchyme migrates

Question 13

The Maxillary and Mandibular Swellings

Answer 13

•the paired first pharyngeal arches only give rise to the mandibular processes.
•Maxillary processes originate as separate (delayed) swellings rostral to the mandibular processes.
> Invaded by distinct population of late migrating CNCC

Question 14

The Nasal Placodes
coordinated?
how they form?

Answer 14

also form along with the arches and other facial structures, coordinated
•Formation and invagination of nasal placodes (thickening of ectoderm) in Frontonasal Prominence (FNP) similar to how the neural tube forms

Question 15

Two types of morphological processes for ‘joining’ tissues

Answer 15

merging and fusion

Question 16

Merging, examples

Answer 16

joining of two masses already partly in contact), 5th week
•Merging of Maxillary (MXP) & Lateral Nasal Processes (LNP)
•Medial merging of Mandibular Processes (MNP)

Question 17

fusion, examples
when?
forms?

Answer 17

(joining of two separate tissue masses), 6th week
•Contact-dependent fusion between MNP and MXP/LNP
ØForms the primary palate and nares (nostrils)

Øcf. Secondary palate (future roof of mouth) arises later from the medial aspects of the MXPs > palatal shelves.

Question 18

independent Growth of the Craniofacial Complex

Answer 18

•After immigration of cranial neural crest cells, growth & morphogenesis
of the face is controlled by ongoing epithelial-mesenchymal interactions
=INDEPENDENT FROM REST OF BODY

Question 19

what determines facial form? example experiment

Answer 19

NCC
Cranial neural crest cells (CNCC) primarily determine facial form/shape
duck to quail experiment

Question 20

The Ectoderm in Growth & Patterning for the face
boundaries of expression?
what must be expressed?

Answer 20

defined boundaries of expression in facial ectoderm will define the location of facial features
Neural expression of Shh/Fgf8 precedes (and is required for) the ectodermal expression

Question 21

shh and fgf8 for facial ectoderm locations

Answer 21

Shh > ventral facial ectoderm; Fgf8 > dorsal facial ectoderm

Question 22

Ectodermal Factors Instructing Facial D-V Patterning
where from? cause and determine what?
the precise shape depends on?

Answer 22

Secreted factors from the FEZ can direct outgrowth of the underlying CNCC and determines D-V pattern of the FNP

Øbut precise shape depends upon pattern information inherent in the neural crest.

Question 23

facial ectoderm functions

Answer 23

support/direct outgrowth of facial structures
guides CNCC differentiation (interrelation between the ectoderm and CNCC)
facilitates timely fusion of processes via signaling

Question 24

facilitation of fusion by the ectoderm occurs where?

Answer 24

Fusion establishes the primary palate>goes on to form the alveolus & lip proper

Question 25

why is full fusion required?

Answer 25

Full fusion is required to ensure the alveolar bone is continuous

Question 26

clefts
commonality?
where could it originate?
other issues?

Answer 26

Cleft lip +/- cleft primary palate
Third most common birth defect (~1 in 700 births world-wide)
can originate from ectoderm or CNCC, others?
need to appreciate possible associated problems.

Question 27

The Secondary Palate/ palatal shelves form from?

when formed?

Answer 27

Palatal shelves=condensations of CNCC mesenchyme

•Secondary palate forms well after the primary palate/lip (10th week vs 7th week)

Question 28

steps to palatal formation

ossification when?

Answer 28

1. Growth (either side of tongue), usually downward until tongue drops
2. Elevation & rotation
3. Medial growth & fusion at midline in middle and with nasal septum, spreads anterior and posterior

** Ossification of the secondary palate (osteoblasts derived from CNCC) begins
just before palatal development complete

Question 29

cleft secondary palate

frequency and causes

Answer 29

(~1 in 1000 births world-wide)
•Can result from:
1) poor growth of shelves, 
2) failed elevation, or
3) failed fusion

Question 30

The Tongue & Secondary Palate Closure

Answer 30

Critical that tongue lowers to allow the shelves to rotate to
a position above the tongue

Question 31

how can tongue lowering be affected

Answer 31

Macroglossia (enlarged tongue) can provide a physical barrier to secondary palate closure

Small or retrognathic mandible also associated with failed palatal fusion (Pierre-Robin sequence)> Tongue forced backward and elevated

Question 32

Embryonic Craniofacial Skeleton
cartilage first appears in? then in?
what does this provide?
what does it precede?

Answer 32

Craniofacial cartilage first appears in the mandible and shortly thereafter in the midface and cranial base
> Provides structural support for shaping the growing head
> Precedes ossification [NB: in the face, few cartilages are replaced by bone unlike the axial skeleton (ie. long bones)]

Question 33

Meckel’s Cartilage

Answer 33

• Cartilage of PA1 arises during 7th week (human) > forms template for the mandible.
• PA1 also contributes to two ear ossicles > parts of malleus and incus (and ligaments)

BUT, like most facial cartilages, most is not converted to bone.
Rather… parts degenerate, with caudal aspects forming part of middle ear bones.

Question 34

Development of the Ear

Answer 34

• Formed from independent embryonic structures
• External and middle ear: Derivatives of PA1 and PA2
• Intervening pharyngeal cleft
• Pharyngeal pouch

•Inner ear:
-Arises from thickening of ectoderm (otic placode) dorsal to PA3 at level of hindbrain and subsequent invagination (otic pit)

Question 35

Hillocks of His, coordinated with what other structures development?

Answer 35

formed from BA 1 and 2> gives rise to the external ear

coordinated with internal ear development that occurs

Question 36

Inner and outer
ear malformations
often associated
with?

Answer 36

Inner and outer 
ear malformations 
often associated 
with mandibular 
defects

Question 37

Human Craniofacial Skeletogenesis ossification begins?

Answer 37

around 53 days the man/max have begun ossification

Question 38

Human Craniofacial Skeletogenesis origins of different bones

Answer 38

frontal/viscerocranium derived from NCC whereas the base/ occipital and parietal are formed from mesoderm

superior bones are formed via intramembraneous
inferior bones are formed via endochrondral

Question 39

why know embryological origins

Answer 39

• Knowledge of the embryological origins of clinical presentations is important to appreciate the totality of the patient’s problem as it may:
• merit additional clinical considerations
• prompt more detailed assessment
• impact treatment plans

•What might seem causally unrelated may in fact be of clinical significance > diagnosis