prenatal craniofacial development Flashcards
Coordination of Face & Brain Development
both develop at overlapping time periods
Cranial Neural Crest Cells derivatives
contribute to derivatives of all 3 germ layers in craniofacial development
facial morphogenesis complexity? involves what processes?
Morphogenesis of the face is a complex 3D process involving patterning, outgrowth, fusion and molding of tissues
head/neck at 22 days size
half the embryo
when pharyngeal arches form, how?
how many?
•During 4th week, ventral mesoderm condenses into a series of segmented bilaterally paired, mesenchymal swellings
> ultimately 5 pairs, arising in cranial-caudal order
organization of the arches (layers)
The Early Facial Prominences
growth directions?
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
oropharyngeal membrane breaks down when?
breaks down during 4th week,
Conservation of Facial Morphogenesis
conserved across multiple species; in early stages we look similar to other species
Pharyngeal Arch growth driving factor
majority of the growth and morphological change in facial tissue masses is driven by the invading cranial neural crest-derived mesenchyme.
pahryngeal clefts and pouches
pouch: inside
cleft: outside
what effect does the migrating NCC have on mesoderm
mesoderm derived mesenchyme will restrict as the NCC mesenchyme migrates
The Maxillary and Mandibular Swellings
•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
The Nasal Placodes
coordinated?
how they form?
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
Two types of morphological processes for ‘joining’ tissues
merging and fusion
Merging, examples
joining of two masses already partly in contact), 5th week
•Merging of Maxillary (MXP) & Lateral Nasal Processes (LNP)
•Medial merging of Mandibular Processes (MNP)
fusion, examples
when?
forms?
(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.
independent Growth of the Craniofacial Complex
•After immigration of cranial neural crest cells, growth & morphogenesis
of the face is controlled by ongoing epithelial-mesenchymal interactions
=INDEPENDENT FROM REST OF BODY
what determines facial form? example experiment
NCC
Cranial neural crest cells (CNCC) primarily determine facial form/shape
duck to quail experiment
The Ectoderm in Growth & Patterning for the face
boundaries of expression?
what must be expressed?
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
shh and fgf8 for facial ectoderm locations
Shh > ventral facial ectoderm; Fgf8 > dorsal facial ectoderm
Ectodermal Factors Instructing Facial D-V Patterning
where from? cause and determine what?
the precise shape depends on?
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.
facial ectoderm functions
support/direct outgrowth of facial structures
guides CNCC differentiation (interrelation between the ectoderm and CNCC)
facilitates timely fusion of processes via signaling
facilitation of fusion by the ectoderm occurs where?
Fusion establishes the primary palate>goes on to form the alveolus & lip proper
why is full fusion required?
Full fusion is required to ensure the alveolar bone is continuous
clefts
commonality?
where could it originate?
other issues?
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.
The Secondary Palate/ palatal shelves form from?
when formed?
Palatal shelves=condensations of CNCC mesenchyme
•Secondary palate forms well after the primary palate/lip (10th week vs 7th week)
steps to palatal formation
ossification when?
- Growth (either side of tongue), usually downward until tongue drops
- Elevation & rotation
- 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
cleft secondary palate
frequency and causes
(~1 in 1000 births world-wide) •Can result from: 1) poor growth of shelves, 2) failed elevation, or 3) failed fusion
The Tongue & Secondary Palate Closure
Critical that tongue lowers to allow the shelves to rotate to
a position above the tongue
how can tongue lowering be affected
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
Embryonic Craniofacial Skeleton
cartilage first appears in? then in?
what does this provide?
what does it precede?
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)]
Meckel’s Cartilage
- 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.
Development of the Ear
- 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)
Hillocks of His, coordinated with what other structures development?
formed from BA 1 and 2> gives rise to the external ear
coordinated with internal ear development that occurs
Inner and outer
ear malformations
often associated
with?
Inner and outer ear malformations often associated with mandibular defects
Human Craniofacial Skeletogenesis ossification begins?
around 53 days the man/max have begun ossification
Human Craniofacial Skeletogenesis origins of different bones
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
why know embryological origins
- 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
