Embryology Flashcards
Review Early Embryonic Development briefly. Describe the Pharynx
[*] Neural tube forms in week 3
[*] By the end of week 4 the embryo has folded – the primitive gut tube including the primitive pharynx has formed
[*] In early week 4, the face has no distinguishing external features BUT tissues/tissue systems that will develop into head and neck represent ~1/2 length of embryo.
The pharynx extends from the base of the skull to the inferior border of the cricoid cartilage of the larynx:
- Nasal: superior to soft palate
- Oral: between soft palate and larynx
- Laryngeal: posterior to the larynx
What are the branchial arches?
The branchial arches/pharyngeal arches/pharyngeal apparatus are a sequence of ridges which form in the lateral walls of the embryonic pharynx (a system of mesenchymal proliferations in the neck region of the embryo after migration of neural crest cells occur). They bulge into the lumen of the pharynx and onto the outside of the future face and neck regions. Externally the arches are covered by ectoderm, internally by endoderm.
What is the Pharyngeal Apparatus
The FNP and PA constitute the pharyngeal apparatus. The FNP is an unpaired structure – underlying it is the developing brain. The pharyngeal arches are paired structures and develop in sequence, decreasing in size.
[*] It is complex tissue system and begins to appear in the fourth week. Its development is closely tied in with the development of the cranial nerves and blood supply of the head, and many systems of the body, notably the brain, CVS and special sensory organs.
[*] All the arches have the same composition of these contributing germ tissues – an outer covering layer of ectoderm, a large mesoderm core causing expansion and an endoderm lining (inside the primitive gut tube – the pharyngeal part). Then remodelling occurs.
Each arch has an associated artery, nerve and cartilage bar
Describe the development of the neural tube and the formation of the 3 vesicles
[*] Notochord signals cause overlying ectoderm to thicken to create a neuroectoderm => slipper shaped neural plate
[*] Edges elevate out of the plane of the disk and curl towards each other, creating the neural tube.
[*] *The ectoderm develops into structures that will keep us in contact with the external environment (CNS, ear, eye etc)
[*] The anterior (cranial-most) end of the neural tube begins to form the brain. First enlargement/dilation of the cranial part occurs. Then 3 vesicle stage (representing 3 key areas in the brain)
- Prosencephalon = forebrain
- Mesencephalon = midbrain
- Rhombencephalon = hindbrain
How many branchial arches are there? What are branchial pouches and clefts?
[*] The branchial arches become highly modified and give rise to a wide variety of structures in the head and neck.
[*] Their development is also closely tied in with the arrangement of the cranial nerves and blood supply of the head.
[*] Theoretically there are 6 branchial arches, but the fifth one is rudimentary and disappears or merges with the fourth.
- On the outside of the head, the arches are separated by branchial grooves (clefts).
- On the inside of the pharynx, they are separated by the branchial pouches. The grooves and the pouches meet end-on and are separated only by a thin sheet, the branchial membrane, made of ectoderm on the outside and endoderm on the inside.
The first and second arches are the largest. A flap of tissue from the second arch grows down to cover the third-sixth arches and grooves and creating a space, the cervical sinus. This is normally obliterated but remnants may persist as branchial cysts in the neck.
What is inside each branchial arch?
Inside each branchial arch is an artery, a vein, a cranial nerve and some mesenchyme.
The mesenchyme is of mixed origin. Some of it is mesodermal but most of it comes from neural crest cells which migrate into the arches from the developing nervous system.
[*] Mesoderm cells become muscles
[*] Neural crest cells give rise to bone or cartilage.
Describe how the cranial nerves are derived embryologically and how are they are classified
[*] 12 pairs: highly specialised and non-segmental (compared to a segmental spinal nerve, the segmental arrangement is lost)
[*] Classified on the basis of function AND embryological origin:
- Somatic efferent
- Special sensory
- Nerves of the pharyngeal arches - each will contain some or all of the following types of nerves:
- Somatic and visceral afferent (sensory) from skin and mucous membranes
- Visceral motor (autonomic)
- Special visceral motor or branchial motor to striated muscles e.g. facial expression
[*] All except CNI & II are derived from mid- or hind-brain
[*] CN V, CN VII, CN IX & CN X have mixed sensory and motor functions and supply the derivates of the pharyngeal arches.
[*] CN XI (cranial accessory) and CNXII also have relationship with pharyngeal arch system.
What is the Nerve of the 1st Arch?
Trigeminal Nerve
[*] Principal sensory nerve of the skin – supplies the skin of the face and lining of mouth and nose
[*] Motor innervation to muscles of mastication and muscles derived from mandibular process
What are the Nerves of the 2nd and 3rd Arches?
CN VII – Facial Nerve
[*] Nerve of the second arch
[*] Passes through stylomastoid foramen and parotid gland (therefore affected in parotid gland pathology)
[*] Mostly motor: muscles of facial expression and muscles derived from the 2nd pharyngeal arch
[*] Small sensory component: taste buds in anterior 2/3 tongue
CN IX – Glossopharyngeal Nerve
[*] Nerve of the third arch
[*] Provides motor innervation to the stylopharyngeus muscle and provides general and special sensory innervation to posterior 1/3 of tongue
What are the Nerves of the 4th and 6th Arches?
CN X – Vagus nerve
[*] Nerve of the 4th and 6th arches
[*] 4th Arch - Superior Laryngeal Nerve
- Cricothyroid
- Constrictors of the pharynx
[*] 6th Branch - Recurrent Laryngeal Nerve
- Intrinsic muscles of the larynx
What are the Arterial and Nerve derivatives of the Branchial Arches?
The Pharyngeal arches are arranged around aortic arch vessels.
Arteries and nerves:
[*] Aortic sac lies in the floor of the pharynx.
[*] 1st and 2nd Arch arteries disappear (regress)
[*] 3rd Arch artery = Internal Carotid Artery
[*] 4th Arch artery = arch of aorta (L) and brachiocephalic artery (right)
[*] 6th Arch artery = “pulmonary arch”
What are the Musculoskeletal derivatives of the Branchial Arches?
Each of the pharyngeal arches develops a neural crest-derived cartilage bar due to communication between the neural crest cells and the mesoderm
Describe the 1st Arch Cartilage
1st arch Cartilage: Meckel’s
[*] The 1st arch divides into maxillary and mandibular prominences
[*] Mandibular prominence develops into the prominent Meckel’s cartilage (cartilage bar undergoes remodelling)
- Develops into 1st and 2nd middle ear ossicles: Malleus and incus
- Provides “template” for mandible which forms by membranous ossification
Describe the 2nd Arch Cartilage
2nd arch cartilage: Reichert’s
[*] Also contributes to middle ear development – develops into stapes (3rd middle ear ossicle)
[*] Additional skeletal contributions are styloid process and the lesser cornu and upper body of the hyoid bone.
[*] The remainder of the hyoid bone is derived from 3rd arch cartilage.
Describe the derivatives of the branchial clefts/grooves
[*] All disappear except the first, between the first and second arches. It becomes the external auditory meatus of the ear.
[*] The external ear itself (auricle) arises from swellings which form around the entrance to the meatus
[*] The 2nd arch grows down to cover others, obliterating all the other clefts.
[*] But there can be remnants:
- If the cervical sinus is not obliterated, cysts or fistulae can occur.
- Cysts are enclosed remnants and fistulae are remnants that maintain an opening to the external environment
- These cysts and fistulae can occur anywhere along the anterior border of the SCM.
What are the derivatives of the branchial pouches?
[*] The human embryo has four pairs of pharyngeal pouches; the fifth is rudimentary. The epithelial endodermal lining of the pouches give rise to a number of important organs
[*] The 2nd pouch is colonised by lymphoid precursors (tonsils) and the 3rd and 4th ones divide into dorsal and ventral tubes.
[*] Pharyngeal gut tube – glandular derivatives
Pouch 1: Eustachian tube and middle ear cavity
Pouch 2: Crypts of palatine tonsil (epithelial proliferation, followed by colonisation by lymphoid precursors)
Pouch 3:
- Dorsal part – inferior parathyroid
- Ventral part – thymus (important gland for immunological development then regresses during childhood)
Pouch 4:
- Dorsal part – superior parathyroid
- Ventral part (ultimobranchial body) – C cells of thyroid
Which derivatives does the middle ear have?
[*] The ossicles become suspended in the tympanic (middle ear) cavity. The ossicles are cartilage bar derivatives (Meckel’s/Reichert’s)
[*] The tympanic cavity and auditory tube (allows tympanic cavity air to equilibrate with atmospheric air) are first pharyngeal pouch derivatives.
Describe the development of the eye
[*] An outgrowth of the forebrain interacts with the surface ectoderm in the head region of the embryo initiating the development of the eye. The functional and supporting elements of the established eye are formed through complex interactions of these embryological tissues.
[*] First an outgrowth forms on each side of the diencephalon, known as the optic vesicle. It will give rise to the retina, iris and ciliary body of the eye.
[*] It grows out towards the surface ectoderm on each side of the head.
[*] Signalling molecules released by the optic vesicle stimulate changes in the ectoderm leading to the formation of the lens and cornea. The ectoderm forms a localised thickening or lens placode opposite the optic vesicle.
[*] Simultaneously the optic vesicle and the lens placode become cup-shaped (invagination). The lens then becomes a closed vesicle and sinks beneath the surface ectoderm; ectoderm closes over it, and will become the cornea.
[*] Mesenchyme cells arrange themselves around the developing lens and retina to form the choroid and sclera.
[*] The muscles that move the eye are derived from somites. Initially the eyes lie on the sides of the head. Growth of the maxillary prominences towards the midline gradually shifts them to the front.
Gross anomalies of eye development may occur during these early stages. They include cyclopia (single midline eye), anophthalmia (absence of eye or eyes) and microphthalmia (abnormally small eyes).
Describe the development of the eyelids and the positioning of the eyes
Eyelids:
- Eyelids begin to develop at the end of the embryonic period (Week 8). They are fused together during the second trimester and reopen in the third.
Positioning of the eyes
- Eye primordial are positioned on the side of the head.
- As facial prominences grow (crucially enlargement of the maxillary prominence), the eyes move to the front of the face – binocular vision
Consider the development of the Ear
[*] The ear is comprised of 3 distinct structures, internal, middle and external. Each has a discrete embryological origin.
[*] The pharyngeal apparatus of the developing head and neck region of the embryo make important contributions to the development of all parts of the ear.
[*] External auditory meatus develops from the 1st pharyngeal cleft.
[*] Auricles develop from proliferation within the 1st and 2nd pharyngeal arches surrounding the meatus.
- 1st Pharyngeal Arch: Malleus, Incus
- 2nd Pharyngeal Arch: Stapes
[*] Positioning of the ears:
- External ears develop initially in the neck.
- As mandible grows (to allow tongue to drop etc, it pushes the ears up)- the ears ascend to the side of the head to lie in line with the eyes.
- Al common chromosomal abnormalities have associated external ear anomalies
What drives development of the face?
[*] Expansion of the cranial neural tube
[*] Appearance of a complex tissue system associated with:
- The cranial gut tube
- The outflow of the developing heart
[*] Development of the sense organs
[*] The need to separate the respiratory tract from the GI tract
Describe the Neural Crest including migration of the neural crest cells
Neural Crest: a specialised population of cells (specialised form of ectoderm) that originates within the neurectoderm.
[*] A “fourth germ lineage”
[*] Cells of the lateral border of the neuroectoderm become displaced from the neural tube and enter the mesoderm. They migrate and contribute to a variety of head and neck structures, become widely distributed throughout the body including face development
Which pharyngeal arches contribute to the face?
[*] Facial skeleton is derived from the frontonasal prominence and the 1st pharyngeal arch. (neural crest of 1st pharyngeal arch)
[*] Muscles of mastication (allow us to chew) are derived from Ph Arch 1 derivatives - mesoderm of the 1st pharyngeal arch
[*] Muscles of facial expression are Ph Arch 2 derivatives - mesoderm of the 2nd pharyngeal arch (NB: these muscles have no bony attachments)
Describe the Facial Primordial
Facial primordial (so large it has 2 prominences)
[*] 1st Pharyngeal Arch
[*] Frontonasal prominence (FNP)
- Surrounds ventro-lateral part of the forebrain.
- Primordia of eyes
Describe the development of the face
The Face: the first evidence of face development is the appearance of a depression in the ectoderm on the ventral aspect of the head. This is the stomatodaeum (buccopharyngeal membrane), the site of the future mouth.
[*] Five folds (prominences/processes) form around the stomatodaeum to create the face.
- Superiorly, in the midline, is a single frontonasal prominence (process). It will form the forehead, bridge of the nose, upper eyelids and the mid-section of the upper lip (philtrum)
- Laterally paired maxillary prominences (processes) form the middle third of the face, the upper jaw and most of the lip and sides of the nose.
- Paired mandibular prominences (processes) form the lower third of the face, including the lower jaw and lip. They are positioned inferolaterally.
[*] The prominences consist of mesenchyme and a covering of ectoderm. The maxillary and mandibular prominences are derivatives of the 1st pharyngeal arch.
[*] Eventually they will fuse together to complete the face.
[*] Facial clefts and cleft lip palate result from failure of fusion
Describe the first part of nose development (up to the formation of the primary palate)
the first evidence of nose formation is the appearance of bilateral ectodermal thickenings (nasal placodes) on the ventrolateral aspect of the frontonasal prominence.
[*] These invaginate (sink) and form deep pits, the nasal pits.
[*] The entrance of each pit is the future nostril.
[*] A horseshoe-shaped ridge forms around the entrance to each nostril. The ‘arms’ of the horseshoe are the medial and lateral nasal prominences (processes).
[*] The deepening nasal pits lie dorsal to the stomodaeum, separated by only a thin sheet of cells, the oronasal membrane. This disappears.
[*] After the oronasal membrane disappears, the oral cavity and nasal cavity are continuous. The separation of the oral and nasal cavities requires the development of the palate.
- Palate development involves the maxillary prominences and the medial nasal prominences. Maxillary prominences grow medially, pushing the nasal prominences closer together in the midline. Maxillary prominences fuse with medial nasal prominences.
- The medial nasal prominences then fuse in the midline, separating the nostrils from the mouth and forming the philtrum of the upper lip and a small midline component of the palate, the primary palate or premaxillary portion.
What does fusion of the medial nasal prominences create?
Fusion of the medial nasal prominences creates the intermaxillary segment – gives rise to
- Labial component: philtrum
- Median part of the maxillary bone with its four incisor teeth
- Primary palate
What is the main part of the definitive palate? How is it formed?
Main part of definitive palate is secondary palate.
A palatal shelf grows from each maxillary prominence towards the midline. They fuse with each other and with the primary palate. Fusion creates the secondary palate and separates the nasal cavity from the oral cavity.
Describe the growth of the palatal shelves and what is happening in the meantime to the mandible and nasal septum
The palatal shelves grow vertically downwards into the oral cavity on each side of the developing tongue.
Meanwhile the mandible grows large enough to allow the tongue to “drop”, allowing the palatal shelves to grow towards each other and fuse in the midline.
The nasal septum develops as a midline down-growth and ultimately fuses with the palatal shelves.
What is meant by the dual origin of the lip and palate?
What is a Cleft Palate? Describe the different types
[*] Cleft palate (relatively common structural defect) results from failure of one or both palatal shelves to reach the midline or fuse with its counterpart
- Lateral cleft lip: failure of fusion of medial nasal prominence and maxillary prominence
- Cleft lip and palate: combined with failure of palatal shelves to meet in midline
- Infants find suckling difficult
Palate is formed from palatal shelves which grow medially into oral cavity from the maxillary prominence.
Once mandible has enlarged sufficiently to allow the tongue to “drop”, the palatal shelves meet in the midline and fuse.
Cleft lip and palate results from failure of FNP to fuse with Max P and failure of palatal shelves to fuse.
So the optic placode gives rise to the sense of vision, the nasal placode gives rise to the sense of smell….what gives rise to the sense of hearing and balance?
[*] Otic placodes, like the Optic/Olfactory Placodes are ectoderm that thickens before sinking. The Otic placodes invaginate, forming the auditory vesicles
[*] The auditory vesicles ultimately develops into membranous labyrinth
- Cochlea – hearing
- Semi-lunar canal system – sense of balance
Describe the growth of the posterior lobe of the Pituitary Gland
The Posterior Lobe is derived from the developing brain. A down-growth from the Diencephalon forms in the midline, called the Infundibulum.
The part of the Diencephalon from which the Infundibulum arises becomes the floor of the hypothalamus.
The connection between the Diencephalon and the Infundibulum becomes the Pituitary Stalk.
The Infundibulum extends down towards the roof of the developing oral cavity (towards the developing pharynx), retaining its connection with the brain (pituitary stalk). Nerve fibre tracts develop in the stalk, growing down from the hypothalamus.
What is happening at the same time as the down-growth of the infundibulum?
At the same time as the infundibulum is forming, an out-pocketing of ectoderm of the stomatdeum, an evagination of the roof of the (oro)pharynx, grows up to meet it. It is known as Rathke’s Pouch.
- It loses its connection with the roof of the mouth and comes to lie anterior to the infundibulum and wrap around the pituitary stalk.
- The point of confluence will be the roof of the developing pharynx.
- The cells of Rathke’s pouch differentiate into the endocrine cells of the anterior pituitary.
A network of blood vessels, the Hypophyseal Portal System, functionally links the anterior lobe to the hypothalamus and posterior lobe.
Persistent remnants of Rathke’s pouch may form cysts.
Give an overview of the development of the tongue
The branchial arches curve around the lateral walls of the mouth and pharynx. Left and right arches meet in the midline ventrally. The tongue and the thyroid gland arise where the branchial arches meet.
The tongue appears in the 4th week, about the same time that the palate begins to form. It lies partly in the oral cavity and partly in the (floor of) pharynx. It is highly mobile (in order to perform speech and mastication functions). The lingual frenulum tethers the tongue to the floor of the oral cavity.
It is composed of intrinsic and extrinsic muscles.
5 separate components come together in its development- it receives a component from each of the pharyngeal arches
Describe the components that give rise to the tongue. What happens if the lingual frenulum is too short?
Two Lateral Lingual Swellings
- 1st Pharyngeal Arch
Three Medial Lingual Swelling
- 1st Pharyngeal Arch
- Tuberculum Impar
- 2nd and 3rd Pharyngeal Arches
- Cupola
- 4th Pharyngeal Arch
- Epiglottal swelling
The Lateral Lingual Swellings over-grow the Tuberculum Impar.
The 3rd Arch component of the Cupola overgrows the 2nd Arch component (the contribution of the 2nd arch has thus been obliterated)
Extensive degeneration occurs, freeing the tongue from the floor of the oral cavity, except from the Lingual Frenulum. This is the beginning of the mobility of the tongue.
If the lingual frenulum is too short in neonates, it can cause problems with suckling, feeding or speech.
Describe how the anterior 2/3rds of the tongue and the posterior 1/3rd of the tongue is formed. Do the branchial arches give rise to the extrinsic or intrinsic muscles of the tongue?
The Anterior two thirds of the tongue:
- The median tongue bud (or tuberculum impar) forms from floor of the pharynx at the level of the second branchial arch.
- Paired distal tongue buds form in front of the tuberculum imp and eventually overgrow and absorb it. The distal tongue buds originate from the first branchial bud
The poster third of the tongue:
- A single swelling, the copola forms in the midline from the second branchial arch.
- A larger swelling, the hypobranchial eminence arises from the third and fourth arches behind the copola. It expands and absorbs the copola, forming the posterior third of the tongue (3rd arch) and epiglottis (4th arch).
The anterior and posterior parts of the tongue expand and fuse with each other.
The line of fusion is seen in the adult as sulcus terminalis.
The branchial arches do not give rise to the extrinsic or intrinsic muscles of the tongue, only to connective tissue and mucosa. Muscles are derived from small somites which arise in the occipital region and migrate into the developing tongue.
Describe the General Sensory Innervation to the tongue
Anterior Two Thirds
- Lingual Nerve (CN V3 – Mandibular Branch of the Trigeminal)
- Nerve of 1st Pharyngeal Arch
- (also from CN IX?)
Posterior Third
- Glossopharyngeal Nerve (CN IX)
- Nerve of 3rd Pharyngeal Arch
- (Also from CN X?)
Describe the Special Sensory Innervation to the Tongue
Anterior Two Thirds
- Chorda Tympani (CN VII – Facial Nerve)
- Nerve of 2nd Pharyngeal Arch, but passes into the 1st Pharyngeal Arch through the middle ear (gets past obstacle – the 1st pharyngeal pouch)
- Tastebuds develop as distinct papillae
Posterior Third
- Glossopharyngeal Nerve (CN IX)
- Nerve of 3rd Pharyngeal Arch
- (Also from CN X?)
Remember: mucosa of anterior 2/3s derived from Ph As1 and 3. Mucosa of posterior 1/3 derived from Ph As 3 and 4.
Describe the motor innervation of the tongue
Both the intrinsic and extrinsic muscles of the tongue develop from myogenic precursors that migrate into the developing tongue (the floor of the pharynx) to populate the parenchyma.
Palatoglossus
- Vagus nerve (CN X)
All other muscles of the tongue
- Hypoglossal Nerve (CN XII)
Describe the beginning of the development of the thyroid gland
The Thyroid gland is the first endocrine gland to develop. It first arises in the midline of the floor of the pharynx during the fourth week, as an epithelial outgrowth, the thyroid diverticulum. It appears in the floor of the pharynx as an expansion of mesenchyme, between the Tuberculum Impar and the Cupola. This site of origin lies between the 1st and 2nd branchial arches and is marked in the adult by the Foramen Cecum.
Describe the descent of the thyroid gland
At its point of origin the Thyroid bifurcates, elongates and descends as a bi-lobed diverticulum along the midline of the neck, connected by the Isthmus (the left and right lobes are connected by a narrow isthmus overlying the 2nd and 3rd tracheal cartilages).
During its descent, the thyroid gland remains connected to the tongue by the Thyroglossal Duct
By 7 weeks, the thyroid has reached its final position. The final position of the thyroid gland is in the anterior neck, anterior to pharyngeal gut, hyoid bone and laryngeal cartilages. At this stage the thyroglossal duct usually disappears, but in about 50% of people, a remnant of its distal end may persist as a pyramidal lobe
The foramen cecum closes off but can be seen in the adult as an indentation on the dorsum of the tongue.
Describe the components of the thyroid gland
Follicles form in the thyroid gland at about 11 weeks and start to absorb iodine and store thyroxin as colloid.
Parafollicular (or C cells), which produce calcitonin, migrate into the thyroid gland from the 4th branchial pouch (ultimobranchial body).
What are Thyroglossal Cysts and Fistulae?
Abnormal positions of the thyroglossal duct may persist along the course of the course of the thyroid gland’s descent and may form thyroglossal cysts. These are always midline in position. They are cystic remnants of the thyroglossal duct. Approximately 50% of these cysts are close to, or just inferior to the body of the hyoid bone – the most common sites are the base of the tongue and just inferior to the hyoid bone.
Sometimes a thyroglossal cyst is connected to the outside by a fistulous canal, a Thyroglossal Fistula. Such a fistula usually arises secondarily after rupture of a cyst, but may be present at birth.
