Craniofacial Biology Flashcards
What is Developmental Biology?
The study of the processes by which organs grow and develop.
Define mitosis
the process by which a cell replicates its chromosomes and then segregates them, producing two identical nuclei in preparation for cell division
Define meiosis
a type of cell division in sexually reproducing organisms that reduces the number of chromosomes in gametes
Define apoptosis
the process of programmed cell death
In embryology, what is induction?
the process in which an undifferentiated cell is instructed by specific organisers to produce a morphogenic effect
What are the 3 stages of prenatal development and their time lines?
preimplantation period (first week)
embryonic period (second to eighth week)
fetal period (third to ninth month)
Define the proliferation stage in the embryonic period
a physiological process of cell division that occurs in almost all tissues, resulting in an increase of the number of cells.
Define the differentiation stage in the embryonic period
the process of development during which embryonic cells specialise and diverse tissue structures arise.
Define morphogenesis in embryonic period
the process of development of specific tissue structure or shape
What point in time does the second period (embryonic period) of prenatal development start?
beginning of the 2nd week to the end of the 8th week
what physiological processes make up the embryonic period?
induction
proliferation
differentiation
morphogenesis
maturation
What is the purpose of the 5 processes of embryonic period?
cause the structure of the implanted blastocyst to become, with further development, an embryo.
they also allow the teeth, orofacial structures and other organ structures to develop in the embryo
Define cytodifferentiation
the development of different cell types
Define histodifferentiation
the development of different histologic tissue types within a structure
Define morphodifferentiation
the development of the differing morphology, which makes up its structure or shape, for each organ or system
When does the bilaminar embryonic disc develop from the blastocyst?
second week
when does the trilaminar embryonic disc develop from the bilaminar disc
third week
What week of prenatal development does the disc undergo embryonic folding?
week 4
Tissue interactions appear to be associated with atleast 2 general types of phenomena, what are they?
Instructive
Permissive
What is organogenesis?
the production and development of the organs of an animal or plant
define instructive tissue interactions
the ability of one tissue to determine specific patterns of morphogenesis and differentiation that will develop in an associated tissue. (tells other tissues what to do)
Define permissive tissue interactions
the ability of an interacting tissue to provide certain conditions that is necessary for its committed partner tissue to progress to full expression of its predetermined phenotype. (drives the devlopment of tissue)
an organ starts as an epithelial placode
placodes are embryonic structures that give rise to structures.
epithelial placode is a condensation of which germ layer
epithelial placode is a condensation of the ectoderm layer
What are the 3 distinct regions of the embryonic origins of the skull?
desmocranium
chondrocranium
viscerocranium
When does the posterior fontanelle close?
The posterior fontanelle usually closes by age 1 to 2 months
It may already be closed at birth
When does the anterior frontanelle close?
The anterior fontanelle usually closes sometime within 7 to 19 months
What are fontanelles?
soft spots on an infant’s head where the bony plates that make up the skull have not yet come together
What is craniosynostosis?
A group of disorders where there is a premature fusion of the sutures
What is Apert syndrome?
Brain is expanding at the front and back instead of transversely due to the premature fusion of the lambdoid and coronal sutures
What is turricephaly?
Turricephaly (Tower Head) is a descriptive term for a distinctive head shape often observed in children with syndromic forms of craniosynostosis, in particular, those with Apert syndrome
What is crouzon syndrome?
A type of craniosynotosis
Prevents the brain expanding resulting in protrusion of the eyes and expansion of the front area of the skull
What is plagiocephaly?
Due to premature sagittal and coronal fusion
The head is flattened on one side, causing it to look asymmetrical
What is Trigonocephaly?
premature closure of the metopic suture causing the inability of the frontal bones to grow laterally, thus forming a triangular forehead with an obvious or subtle osseous ridge
What is cloverleaf skull?
an abnormal configuration of the calvaria classified as craniosynostosis, consisting of premature ossification of cranial sutures
What is Treacher Collins Syndrome (TCS)?
A disorder of craniofacial development which effects the way the face develops,
What causes TCS?
the abnormal formation of the first and second branchial arches during 5-8th weeks of human fetal development, leading to profound facial dysmorphism
TCS is both genetically and phenotypically heterogenous, true or false?
True
What type of TC0F1 mutation, leading to TCS ,is the majority of cases?
Deletions
The loss-of-fuction mutations in which gene is responsible for most cases of TCS?
TCOF1
What may the TC0F1 mutations result in which is small and functional?
truncated treacle protein
What protein does TCOF1 encode for?
Treacle
Less common mutations in which genes can cause TCS
POLR1D and POLR1C
What do POLR1D and POLR1C encode for?
subunits of the enzymes RNA polymerase I and III, important in RNA synthesis
what is the importance of the treacle protein?
it is active during early embryonic development in structures that become bones and other tissues in the face.
it also plays a key role in pre-ribosomal processing and the making of the ribosome
What facial bones are most affected by TCS?
Underdeveloped cheek bones, eye sockets, small jaw and chin (micrognathia)
What facial features can be seen in someone with TCS?
eyes that slant downwards, sparse eyelashes, eyelid coloboma
What is the main concern in newborn TCS patients?
respiratory failure due to airway narrowing from craniofacial malformation
Which gene mutation involved in TCS are inherited via an autosomal pattern (not a sex chromosome)
TC0F1
What is the chondocranium also known as?
cranial base
When does the development of the head, face and oral cavity usually take place and end?
Starts around week 4
Usually finishes around week 10
What is the pharyngeal apparatus?
It is made up on the arch, the clefts (grooves), pouches and membranes and gives rise to muscle, cartilage, nerve and blood supply
What are the 4 fundamental aspects of developmental biology?
Proliferation/Growth size
Pattern formation
Morphogenesis - shape
Differentiation - type
What is pattern formation?
The cells differentiating into the correct tissues and the right place
What are dynamic, reciprocal and sequential interactions?
Sequentially - they happen at a specific time
Reciprocal - one cell will control what happens to another and vice versa
Dynamic - Happens between 4-10 weeks (very quick)
What are signalling centres?
the organiser of whats going to occur in that place
What is the signalling gradient?
Only at the right points will the cells make a tissue
What is true fusion?
2 things at either sides of the head need to fuse together, eg. palate fusion
What is cell migration?
Cells move into the area in order to produce what they need to
How many primary germ layers are there and what are they
3
Ectoderm
Mesoderm
Endoderm
Neural crest/Ecto-mesenchyme (not a true layer)
What is the ectoderm layer?
The outer most layer, gives rise to the skin and neural tube
Comes from the epiblast layer
What is the mesoderm layer?
Layer in between the ectoderm and endoderm
Forms from migratory cells of the epiblast layer
Forms just about everything else
What is the endoderm layer?
Innermost layer of the 3 primary germ layers
Forms the gut
Comes from the hypoblast layer
When do the branchial arches start to develop?
days 24/25
What effects how the branchial arches differentiate into different tissues?
The spinal column
What does pharyngeal arch 1 give rise to?
the mandible and maxilla (lower part of face)
Meckel’s cartilage
What does pharyngeal arch 2 give rise to?
Reichart’s cartilage
What is the purpose of Meckel’s cartilage?
Acts as a jaw support during early development and a template for the later forming bones
By week 20 there are only remnants of it left
What is the stomatodeum?
a depression between the brain and the pericardium in an embryo
This forms the oral cavity
When does the pharyngeal arches formation begin?
4th and 5th week
When does the pharyngeal arches formation begin?
4th and 5th week
What is the reason for the difference in each pharyngeal arch?
Because you get different neural crest cells, these are what migrate into the heck and neck region to form these arches
What are the 5 pharyngeal arches?
I - Mandibular arch
II - Hyoid arch
III
IV
VI
What are the 5 pharyngeal arches?
I - Mandibular arch
II - Hyoid arch
III
IV
VI
What does the pharyngeal arches consist of?
Ectoderm - outside
Endoderm - inside (except 1st arch- its a continuation of ectoderm)
Cartilage
Blood vessels and Nerve
Muscle
What is the name of the 1st arch?
Mandibular arch
What does the 1st arch give rise to?
mandibular and maxillary processes
Body of tongue
muscles of mastication
trigeminal nerve
maxillary and carotid arteries
meckel’s cartilage
What does reichart’s cartilage give rise to?
stapes
lesser horn, superior hyoid body
styloid process, stylohyoid ligament
When does Meckel’s cartilage dissapear and what is it replaced by?
week 20, it is replaced by bone
What is the name of the 2nd arch?
hyoid arch
What is the cartilage present in the 2nd arch known as?
Reichart’s cartilage
What does the 2nd arch give rise to?
Muscles of facial expression
thryoid gland and tonsils
facial nerve
reichart’s cartilage
What does meckel’s cartilage give rise to?
forms 2 bones: incus, melleus
forms 2 ligaments: sphenomandibular, sphenomelleolar
What does the 3rd arch form?
greater horn of hyoid
inferior hyoid body
root of tongue
stylopharyngeus muscle
glossopharyngeal nerve
What does the 4th arch form?
thyroid cartilage
pharynx and epiglottis
soft palate muscles
pharyngeal constrictor muscles
vagus nerve
what happens to the 5th arch?
rapidly disappears
what does the 6th arch form?
cricoid + arytenoid cartilages
larynx
muscles of larynx
vagus nerve
What happens to the 2nd-6th clefts?
they disappear as their obliterated by the proliferation of the second arch as it basically grows over the top of it
forms hyoid operculum
Where do the pouches form?
between the arches
what does the first pharyngeal pouch give rise to?
middle ear
what does the 2nd arch pouch give rise to?
palatine tonsil
what does the 3rd arch pouch give rise to?
inferior parathyroid gland
what is formed between pouch 3 and 4?
thymus
what does the 6th arch pouch give rise to?
superior parathyroid gland
what does the 1st pharyngeal groove/cleft form?
external auditory meatus
what obliterates all grooves by week 4/5?
cervical sinus as the neck develops
where do the pharyngeal membranes appear?
the floor of the pharyngeal grooves
What causes branchial fistula/cyst?
failure of the 2nd arch growing down sufficiently over 2nd-4th clefts
What is the fronto nasal process?
prominence in the upper facial area at the most cephalic end of the embryo
What is the cephalic end?
Head end of a structure such as the trilaminar embryonic disc
What is the mandibular processes?
Processes of first branchial arch that fuse at the midline to form mandibular arch
what is the mandibular arch?
lower dental arch with mandibular teeth or the 1st branchial/pharyngeal arch inferior to the stomodeum in the embryo
what is the maxillary processes?
prominence from mandibular arch that grows superiorly and anteriorly on each side of the stomodeum of the embryo
What is the maxillary arch?
upper dental arch in which the maxillary teeth form
what is the nasal placode?
placodes that develop into olfactory organ for the sensation of smell located in the mature nose
what is a placode?
area of ectoderm found at the location of the developing special sense organs on the embryo
what do the maxillary processes give rise to?
the maxillary arch
when is the basic morphology of the face established by the joining of the 5 prominences?
between week 4 and 10
What is the stomodeum?
Mouth development begins with the formation of the stomodeum (mouth pit)
Its an ectodermal depression around which the facial primordia grow and extend to create the oral cavity.
On day 26, maxillary procceses start to grow across and out, what happens to the mandibular process?
the groove is going to start to get less because the proliferation in the centre pushes outwards, therefore rather than there being 2 processes there’s one long process
what are placodes?
round areas of thickened ectoderm which will develop into special sense organs
what gives rise to the nasal pit?
nasal placodes
During week 7 the ectoderm at the floor of this groove invaginates into the underlying mesenchyme to form a tubular structure called what?
nasal lacrimal duct and lacrimal sack
what is the nasal lacrimal duct?
invested by bone during ossification and the maxilla
after birth it functions to drain excess tears from the conjunctivca of the eye into the nasal cavity
when do we have the formation of basic nose structure?
end of week 6
When does true fusion of the medial nasal process and inter maxillary process take place giving rise to the intermaxillary segment?
end of week 7
what does the intermaxillary process give rise to?
philtrum and then later the primary palate
how many teeth will the primary palate consist of?
4 incisor teeth
what is macrostomia?
a congenital deformity resulting from failure of fusion of maxillary and mandibular process
what can too little fusion cause?
macrostomia
large mouth
what is microstomia?
a condition with a small sized-mouth that results in functional impairment such as difficulty with food intake, pronunciation, and poor oral hygiene and cosmetic problems
what can too much fusion cause?
microstomia
small mouth
what happens in week 4 of formation of the face?
primitive stomodeum bounded by fronto nasal process, maxillary and mandibular process
nasal placodes develop into nasal pits
what happens in week 5 of formation of the face?
nasal pit is surrounded by lateral and medial nasal prominence
what happens in week 6/7 of formation of the face?
medial nasal prominences fuse together and fuse with maxillary processes
what does the frontonasal contribute to the face?
forehead
bridge of nose
what does the medial nasal contribute to the face?
philtrum of the lip
crest and tip of nose
what does the lateral nasal contribute to the face?
alae of nose
what does the maxillary contribute to the face?
cheeks
lateral upper lip
streams of what migrate to form areas like the secondary palate?
mesenchyme
when is the first sign of tooth development?
week 6
how does tooth bud formation occur?
thickening of the epitheial band
what happens to the mesenchyme in order to form cartilage?
condensation
mesenchymal cells will differentiate into chondroblasts to start to form the cartilage of the nose
what is the purpose of mesenchymal condensation?
turn into chondroblasts which act as the primary support for the developing maxilla and will form the cartilages of the cranial bases
what is the difference between mesenchyme cells and ectomesenchyme cells?
Mesenchyme contains loose cells that migrate easily to form the ground tissue of collagen, and bone and cartilage tissue while ectomesenchyme contains neural crest cells and forms the tissues of neck and cranium
when is the maxilla bone formed?
6-7th week
when is the maxilla bone formed?
8th week
when is the palate and nasal capsule bone formed?
8th week
what are the 2 methods of osteogenesis?
intramembranous
endochondral
what is intramembranous ossification?
formation of an osteoid within 2 dense connective tissue sheath sheets, which then eventually replaces the connective tissue
During intramembranous ossification, mesenchymal cells differentiate into osteoblasts from osteoid
what is endochondrial ossification?
the mesenchymal cells start to grow around the side of the cartilage and deposit around that
what is cartilage made of?
chondroblasts
chondrocytes
what are the 3 types of cartilage?
hyaline
fibrocartilage
elastic
what are the 3 main functions of cartilage?
forms the supporting framework
forms articulating surface of bones
forms template for growth and development
what connective tissue growth factor is involved in meckel’s cartilage development?
CCN2
What are the 3 mandibular secondary cartilages?
condylar
coronoid
symphyseal
when does the formation of the palate start and finish?
starts at around week 6
finished by week 12
what is the purpose of the primary palate?
demarcates the oral and nasal cavities
what does the primary palate give rise to?
anterior 1/3 of the hard palate
what does the secondary palate give rise to?
posterior 2/3 of the hard palate
what happens in week 7/8 of palate fusion?
mesenchymal cells differentiate into osteoblasts
what is is the purpose of the secondary palate?
separates nasal airway and oral cavity
what week do mesenchymal cells migrate in to form nasal septum and palatal shelves
week 6
when does the tongue withdraw townwards allowing palatal shelves to flip up into the horizontal orientation?
beginning of week 8, depending on gender, sometimes sooner in males
why does the tongue withdraw during palatal development?
due to the head lifting from the cardiac plate
what are the 2 theories behind palatal shelf elevation?
forces extrinsic to the palate - e.g the tongue
intrinsic forces generated within the palate
when do the palatal shelves start to touch?
end of week 8
how long does the zipping action take from the front to the back of the oral cavity?
4 weeks
what is left at the midline once the shelves have migrated and met in the middle?
a group of midline epithelial cells
why do the shelves not fuse with the epithelia of the tongue?
because the glycoproteins of the tongue are different than the palatal shelves and epithelium only sticks to the same epithelium
what are the 3 theories on how the midline cells disintegrate?
epithelial-mesenchyme transition
apoptosis
migration
explain the epithelial-mesenchyme transition
a set of epithelial cells don’t need to be epithelial cells anymore, mesenchymal cells job is to make the matrix of the upper palate, rather than make the cells redundant, you make them into mesenchymal cells. Some evidence of this transition to happen.
explain the apoptosis theory behind palate fusion?
programmed epithelial cells to die off, they’ve done their job, and aren’t needed anymore so they are just going to die off.
Explain the migration theory behind palate fusion?
The cells migrate towards the nasal or oral edge, moving out from the midline, where they just become epithelial cells.
failure of fusion can lead to what?
cleft palate
what is epithelial remnants?
some of the epithelial cells either don’t migrate, die off or transition into mesenchymal cells, can cause epithelial cell rests, this causes pain in roof of mouth
is cleft palate more common in males or females and why?
females
due to process starting one week later
The confluence of sagittal and lambdoid sutures at the back of the skull make up what?
posterior fontanelles
The confluence of the sagittal, coronal and frontal sutures make up what?
anterior fontanelles
when does the posterior fontanelle close?
3-6 months postnatally
when does the anterior fontanelle close?
1.5-2yrs postnatally
