Craniofacial Biology Flashcards
What is the incidence of treacher Collins syndrome?
1:50,000 live births
What causes TCS?
Abnormal formation of the first and second branchial arches during the 5th to 8th weeks of human fetal development
What are the main characteristics of TCS?
- Facial dysmorphism (particularly of the cheek bones, eye sockets and jaw)
- absent, small or unusually formed ears
- potential loss of vision and hearing
What type of gene and mutation is most commonly the cause of TCS?
Gene: TCOF1
Mutation: loss of function mutation
What protein does the gene, TCOF1 encode?
Treacle
Aside from TCOF1, what are the other genes, which mutations cause TCS?
POLR1D and POLR1C
What is the main concern in a newborn with TCS?
Respiratory failure due to narrowing of airway from Craniofacial malformation
Mutation of which gene accounts for 70-93% of TCS individuals?
TCOF1
Mutation of which genes account for 11-23% of TCS individuals?
POLR1D and POLR1C
What type of mutations are the majority of TCOF1 mutations?
Deletions
What effect does mutation of TCOF1 have on treacle protein?
Results in truncated treacle protein which is small and non-functional
What protein is active during early embryonic development in structures that become bones and other tissues in the face?
Treacle
What is the key role of treacle?
Pre-ribosomal processing and making of ribosome
The study of the processes by which organs grow and develop
Developmental biology
The process by which a single parent cell divides to make two new daughter cells ( total number of chromosomes maintained)
Mitosis
A special form of cell division involving two rounds of division that result in four cells with only one copy of each chromosome
Meiosis
The process by which an undifferentiated cell is instructed by specific organisers to produce a morphogenic effect
Induction
An organiser is part of an embryo, what does it influence?
Influences another part of the embryo to direct histological and morphological differentiation
What is ‘patterning’ and when does it occur?
Patterning is certain physiologic processes or spatial and temporal events which are key to further development. Occurs during the embryonic period from the 2nd to 8th week of parental development.
The development of different cell types
Cytodifferentiation
The development of different histologic tissue types within a structure
Histodifferentiation
The development of differing morphology, which makes up its structure or shape, for each organ or system.
Morphodifferentiation
During the second week of prenatal development, what develops from the blastocyst, appearing as a three-dimensional but flattened, essentially circulate plate of bilateral cells.
A bilaminar embryonic disc
What general types of phenomena are tissue interactions associated with?
- instructive
- permissive
The ability of one tissue to determine specific patterns of morphogenesis and differentiation that will develop in an associated tissue
Instructive 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 pre-determined phenotype
Permissive tissue interactions
What protein is very important for fusion of palatal shelves during development?
Hyluronase synthase
What virus has been known to lead to craniofacial development issues in newborns?
Zika virus
What are common symptoms of Zika virus?
Fever, rash, conjunctivitis, muscle and joint pain, malaise and headache
What congenital abnormality in regards to craniofacial development is a risk if pregnant woman contracts Zika virus?
Virus can cause microcephaly (baby’s head is much smaller than expected)
What four aspects make up the craniofacial complex?
- cranial vault
- cranial base
- nasomaxillary complex
- mandible
What are the main sutures important for normal fetal development?
- coronal
- sagittal
- lambdoid
- parietal
What is craniosynostosis?
A birth defect in which the bones in a baby’s skull join together too early
What craniosynostosis is this:
A genetic disorder characterised by the premature fusion of certain skull bones
Crouzon syndrome
What craniosynostosis is this:
A type of disorder where the head appears tall with some length and width
Turricephaly
What craniosynostosis is this:
The head is flattened on one side, causing it to look asymmetrical
Plagiocephaly
What craniosynostosis is this:
A condition where the baby’s skull has fused together before birth causing a triangular shape or ridge on the forehead
Trigonocephaly
A cartilaginous joint where bones are joined together by hyaline cartilage, or where a bone is attached to hyaline cartilage
Synchondrosis
Type of ossification where cartilage grows rapidly and is replaced by bone
Endochondral ossification
What is a homeobox gene?
A DNA sequence that regulates large scale anatomical features in the early stages of embryonic development
What two factors are homeobox genes responsible for?
- craniofacial shape and patterning
- patterning of the dentition
How are homeobox genes important in regards to tooth development?
MSX1 &2 in the initiation, developmental position and morphodifferentiation of tooth buds
Condition caused by the disruption of development due to artery bursting
Hemifacial microsomia
When right and left palatal shelves fail to meet and fuse with the nasal septum, what can be the result?
Cleft palate
What plays an important role in the site-specific nature of cell differentiation and proliferation?
Cell-cell interactions
What type of interactions occur between cytokines and matrix macromolecules to mediate cell-cell interactions?
Dynamic and reciprocal
What are the four primary germ layers?
- Ectoderm
- Mesoderm
- Endoderm
- Neural crest/ectoderm-mesenchyme
What germ layer comes from the epiblast layer?
Ectoderm
What germ layer comes from the migratory cells of the epiblast layer?
Mesoderm
What germ layer comes from the hypoblast layer?
Endoderm
What germ layer comes from the ectoderm that migrates into mesoderm to form structures in the head and neck?
Neural crest/ ecto-mesenchyme
At what post-ovulatory age (days) does the branchial arches start to form?
Days 24/25
What cranio-facial structures do the branchial arches develop to form?
Face, pharynx, larynx, naso-cavities, mouth and neck
What happens in the stomatodeum just before 28 days of foetal development?
Group of cells across this area undergo apoptosis allowing growth factors to seep in
What is the stomatodeum?
Developing oral cavity in a foetus
When do pharyngeal arches start to appear?
In 4th and 5th week as neural crest cells migrate into the head and neck region
A typical pharyngeal arch contains?
- artery
- cartilage
- muscle
- nerve
What genes control type of neural crest cell that develops?
Homeobox genes
What 4 components make up the branchial arch system?
- Arches
- Clefts
- Grooves
- Pouches
Which branchial arch disappears very early in development?
5
Which pharyngeal arch is a continuation of the endoderm?
1st arch
Which pharyngeal arch lays the framework for the development of the mandible and maxilla through meckle’s cartilage?
1st arch ( mandibular arch)
what muscles are associated with the 1st pharyngeal arch?
-Muscles of mastication
-anterior belly of digastric
-mylohyoid
-tensor tympani
-tensor veli palatini
what cranial nerve is associated with 1st pharyngeal branch?
Trigeminal nerve ( CN V)
Which arteries does the 1st pharyngeal branch give rise to?
Maxillary artery
Internal carotid arteries
What cartilage is associated with 1st pharyngeal arch?
Meckle’s cartilage
What two bones does meckel’s cartilage give rise to?
- Incus body
- malleus
What two ligaments does meckel’s cartilage give rise to?
- sphenomandibular
- sphenomalleolar
What syndrome is a result of the failure of neural crest cell migration during development of pharyngeal arch 1?
Treacher- Collins Syndrome
What is another name given to the 2nd pharyngeal arch?
Hyoid arch
What cartilage is associated with 2nd pharyngeal arch?
Reichert’s cartilage
What structures does reichert’s cartilage form?
- stapes
- lesser horn and superior hyoid body
- styloid process, stylohyoid ligament
what muscles are associated with the 2nd pharyngeal arch?
Muscles of facial expression
Stapedius
Stylohyoid
Posterior belly of digastric
What nerve is associated with 2nd pharyngeal branch?
Facial nerve (VII)
What artery is derived from 3rd pharyngeal branch?
Internal carotid artery
What nerve is associated with the 3rd pharyngeal branch?
Glossopharyngeal nerve (IX)
What muscles are associated with the 3rd pharyngeal branch?
Stylopharyngeus
What are the skeletal derivates associated with the 3rd pharyngeal branch?
Greater horn of hyoid
Inferior hyoid body
Which pharyngeal arch forms the root of the tongue?
3rd arch
Which pharyngeal arch forms the thyroid gland and tonsil?
2nd arch
Which arteries are given off from the 4th pharyngeal branch?
Right subclavian artery
Aorta
Which cranial nerve is associated with the 4th pharyngeal arch?
Vagus nerve (CN X)
What muscles are associated with pharyngeal arch 4?
Pharyngeal constrictor
Soft palate
What cartilage does the 4th pharyngeal arch form?
Thyroid cartilage
Which pharyngeal arch forms the pharynx and epiglottis?
4th arch
What cartilage is associated with pharyngeal arch 6?
Cricoid and arytenoid cartilages
Which pharyngeal arch forms the larynx?
Arch 6
What muscles are associated with pharyngeal arch 6?
Muscles of larynx
What cranial nerve is associated with 6th pharyngeal arch?
Vagus nerve (CN X)
Which clefts are obliterated by the proliferation of 2nd pharyngeal arch, which grows over the top of them?
2nd-6th clefts
What structure is found between each arch?
Pouches
What does the 1st pouch form?
Middle ear and auditory tube?
What does the 2nd pouch form?
Tonsillar fossa ( palatine tonsil)
What does the 3rd pouch form?
Inferior parathyroid gland
Thymus
What does the 4th pouch form?
Superior parathyroid gland
Post-branchial body
What does pharyngeal groove/cleft 1 form?
External auditory meatus
As the neck develops, what happens to all grooves/clefts, except the first?
They are obliterated by cervical sinus development
Where are pharyngeal membranes found?
In the floor of the pharyngeal grooves
Which pharyngeal membrane becomes the tympanic membrane, while the others are obliterated?
1st pharyngeal membrane
What is the consequence of the 2nd pharyngeal arch failing to enlarge over the 2nd -4th clefts?
Branchial fistula/cyst
Which pharyngeal arch has very little homeobox gene expression?
1st pharyngeal arch
Define the term used for: the prominence in the upper facial area at the most cephalic end of an embryo
Fronto-nasal process
Define the term used for: relating to the head or the head end of a structure
Cephalic end
Define the term used for: the processes of first branchial arch that fuse at the midline to form mandibular arch
Mandibular processes
Define the term used for: lower dental arch with mandibular teeth or the 1st branchial/pharyngeal arch inferior to the stomodeum in the embryo
Mandibular arch
Define the term used for: the prominence from mandibular arch that grows superiorly and anteriorly on each side of the stomodeum of the embryo
Maxillary processes
Define the term used for: upper dental arch in which the maxillary teeth form
Maxillary arch
Define the term used for: placodes that develop into olfactory organ for the sensation of smell located in the mature nose
Nasal placode
Define the term used for: area of ectoderm found at the location of the developing special sense organs on the embryo
Placode
The development and joining of what structures establishes the basic morphology of the face between weeks 4-10?
The five prominences
What are the five prominences that make up the formation of the face?
- Frontonasal prominence
- Maxillary prominences x2
- Mandibular prominences x2
What are the two types of fusion that can occur between prominences?
- “ fusion”- between prominences by elimination of furrow
- True fusion- of separate processes
What forms from the stomodeum, specifically the fused nasal prominence?
Primary palate
At 27 days of development, what starts to form from the nasal placode?
Nasal pit
At 34 days of development what starts to form from the developing otic placode?
The eyes
Where is the nasolacrimal groove/nasal optic furrow found in the developing skull?
Between the lateral nasal prominence and the maxillary prominence
During the 7th week of development, what tubular structures does the nasolacrimal groove form?
Nasolacrimal sac and duct
What is the function of the developed nasolacrimal duct after birth?
It drains excess tears from the conjunctiva of the eye into the nasal cavity
At 6 weeks, what structure does the left and right medial prominences join to form?
The basic structure of the nose ( primordial of bridge and septum)
How is the intermaxillary segment formed in the 7th week of development?
The inferior tips of the medial nasal processes expand laterally and inferiorly to join with the intermaxillary process
what does the intermaxillary process give rise to?
- filtrum
- primary palate
By what week of development is the structure of the face fairly recognisable?
10 weeks
In what week of development is the mouth reduced to it’s final width?
Weeks 7-8
Define macrostomia
An enlargement of the mouth at the oral commissure (too little fusion)
Define microstomia
A small sized mouth due to too much fusion during Craniofacial-facial development
mesenchyme associated with the frontonasal prominence, is from what part of the brain?
Forebrain and midbrain
What part of the brain is mesenchyme associated with the maxillary and mandibular processes from?
Midbrain and hindbrain
At what week in Craniofacial development is the first sign of tooth development, with formation of the primary epithelial band?
Week 6
During what week of Craniofacial development does ossification of the mandible occur?
6-7th week
During what week of Craniofacial development does ossification of the maxilla occur?
8th week
During what week of Craniofacial development does ossification of the primary palate and capsule occur?
8th week
What are the two methods of osteogenesis?
- intramembranous
- endochondral
In intramembranous ossification what do mesenchymal cells differentiate into?
Osteoblasts
What is the major controlling element of pattern formation during development?
Retinoic acids
What are the five growth factor families implicated in facial development? And what do they do?
- BMP
- FGF
- Shh
- Wnt
- Endothelins
Control proliferation, survival and apoptosis
What controls patterning of the facial primordia?
Neural crest cells
What is the prevalence of cleft lip?
1:1000 births
What is the ‘mandibular process’ and what does it give rise to?
An embryological structure which gives rise to the mandible
What cells make up cartilage?
Chondroblasts and chondrocytes
What are the three types of cartilage?
- Hyaline
- Fibrocartilage
- Elastic cartilage
what is the most common type of cartilage?
Hyaline
What are the three functions of cartilage?
- supporting framework of some organs, preventing collapse
- articulating surface of bones
- template for the growth and development of long bones
What do chondroblasts mature into?
Chondrocytes
What is perichondrium?
A dense, irregular layer of fibrous connective tissue that covers the surface of most cartilage in the body
What does the outer layer of cartilage contain?
fibroblasts that produce collagen
What does the inner layer of cartilage contain?
Chondroblasts
What are the two mechanisms of cartilage growth?
- Interstitial growth
- Appositional growth
What is interstitial growth of cartilage?
Chondrocytes grow, divide and lay down more matrix inside the existing cartilage
What is appositional growth of cartilage?
New surface layers of matrix are added to the pre-existing matrix by new chondrobalsts from the perichondrium
What is the main cartilage of the 1st pharyngeal arch?
Meckel’s cartilage
What is the fate of meckel’s cartilage, summarised?
Transforms to sphenomandibular ligament or disappears, absorbed by the growing mandibular bone
What is the full name for the growth factor, CCN2?
Connective tissue growth factor
What is the growth factor CCN2 required for in meckel’s cartilage development?
Accelerates adhesion and aggregation of 1st arch cells, as well as having a significant contribution to mandibular morphogenesis and tooth development
What is the fundamental role of growth factor, CCN2, in ossification?
Acts as a messenger from chondrocytes to osteoblasts, guiding ossification
What two types of ossification are involved in formation of the mandible and identify which is primary and secondary
- Intramembranous (primary)
- Endochondral (secondary)
The process of laying down new bone material by osteoblasts
Osteogenesis
when does initial formation of the mandible occur?
10 weeks in utero
What are the three mandibular secondary cartilages?
- Condylar
- Coronoid
- Symphyseal
What mandibular secondary cartilage is of most importance, disappearing at 20 years of age?
Condylar cartilage
Which mandibular secondary cartilage disappears before birth?
Coronoid cartilage
Which mandibular secondary cartilage disappears before the 1st year after birth?
Symphyseal cartilage
what type of cartilage are secondary growth cartilages?
Fibrocartilage
what type of cartilage growth do secondary cartilages undergo?
Apppositional growth
what type of ossification do secondary growth cartilages undergo?
Endochondral ossification
When does formation of the palate start and end?
Starts at week 6 i.u. And ends at week 12 i.u.
What is the function of the primary palate?
Demarcates oral vs nasal components
Where is the primary palate derived from?
From fused medial nasal prominences
When does ossification of the primary palate occur?
Week 8 i.u.
What is the role of the definitive (secondary) palate?
Separates the nasal airway + oral cavity
What is formation of the definitive (secondary) palate important for?
- mastication : bolus formation
- sensation : taste and texture
- speech
Where do the palatal shelves initial migrate to?
Grow down the sides of the tongue
At what week does the tongue withdraw downwards, allowing space for the palatal shelves to flip and elevate?
Week 8
At what stage in palatal shelve elevation does hyaluronan accumulate?
Prior to elevation
At what week do the lateral palatal shelves contact each other at the midline to form the definitive or secondary palate?
End of week 8
what direction does fusion of the palate occur? Front to back OR back to front?
Front to back
At what week is the secondary palate completely fused?
Week 12
What group of cells are found at the midline once two separate structures make contact in true fusion?
Epithelial cells
What molecules of high specificity are involved in epithelial adhesion?
Sticky surface glycoproteins
To achieve true fusion, what must happen to the midline epithelial cells?
Disintegration
what are the three theories of midline epithelial cell disintegration?
- Epithelial-mesenchymal transition
- Apoptosis of epithelial cells
- Migration to the nasal or oral edge
What are Mesenchymal cells role in the formation of the palate?
Make the matrix of the upper palate
What are the risk factors for cleft palate?
- smoking
- alcohol abuse
- drugs
- viruses
- excess vitamin A
- deficiencies in folic acid
How many hyaluronan enzymes are there? And what are they called?
3
HA synthase 1,2 and 3
Which HN enzyme is mostly expressed during development of the head and neck?
HN2
What is the purpose of the knockout mouse experiment?
To silence the gene of interest to see what effect this has on development
What gene, if ‘knocked out’ will result in cleft palate formation?
TGF beta 3
What two roles do homeobox genes play in Craniofacial development?
- Craniofacial shape and patterning
- Patterning of the dentition
What genes direct migration of neural crest cells into first branchial arch to become ectomesenchyme?
Homeobox genes
What two homeobox genes are involved in the initiation , patterning and morphodifferentiation of tooth buds?
MSX1 and MSX2
What are the different types of single gene mutations?
- autosomal dominant
- autosomal recessive
- x-linked recessive
give an example of a condition that is autosomal dominant in inheritance
Osteogenesis imperfecta
give an example of a condition that is autosomal recessive in inheritance
Cystic fibrosis
give an example of a condition that is x-linked in inheritance
Amelogenesis imperfecta
what is an example of a Craniofacial condition that is autosomal dominant?
Crouzon syndrome
What is the diagnostic feature of van der woude syndrome, commonly mistaken as cleft palate?
Lower lip pits
What are the two clinical symptoms of dentinogenesis imperfecta?
- opalescent dentine that is easily worn
- blue sclerae of eye
Define penetrance
The probability that presence of disease genotype will cause disease
define expressivity
The variation in the severity of expression of a particular gene. Refers to the components of the phenotype that are exhibited in an individual.
Give an example of a condition with variable expressivity
Myotonic muscular dystrophy- inability to quickly relax a muscle after sustained contraction
If an individual is described as having complete penetrance, how will their condition present?
They will express full phenotypic features of a condition
What is required for autosomal recessive inheritance to cause disease?
Two faulty copies of a gene
In an x-linked recessive inheritance, which offspring sex can only be affected if the mother is a carrier?
Male
In x-linked recessive inheritance, female offspring can only be carriers of a disease. True of false?
True
What form of cleft lip has a major manifestation, meaning it’s more likely to cause cleft lip in future offspring?
Bilateral cleft lip
What is the role of folic acid as a dietary supplement regarding neural tube defects?
Has been found to reduce the risk of neural tube defects by 70%
In autosomal recessive inheritance, are the parents of affected individuals typically affected themselves or just gene carriers?
Gene carriers
In autosomal recessive inheritance what are the chances of offspring inheriting two copies of the disease allele?
1 in 4 (25%)
What causes complex multi factorial disorders?
The interactions of variations in multiple genes and environmental factors
Define ‘anticipation’ in terms of genetic disease
Term used to describe genetic disease that increases in severity or is marked by an earlier age of onset with each successive generation
When viewings sections through an embryonic head, what does it mean if meckels cartilage appears close together? And what does it mean when it appears far apart?
meckel’s cartilage is close together at the front of the head, and further apart at the back.
