Embryology Flashcards
What % of newborns have major structural abnormalities?
3%
What forms the bilaminar disc?
Epiblasts and hypoblasts
What is gastrulation?
Formation of the 3 germ layers (ectoderm, mesoderm and endoderm)
During gastrulation, how does the mesoderm form?
Epiblast cells migrate through the primitive groove to lie above the newly formed endoderm and form the mesoderm.
During gastrulation, how does the endoderm form?
Epiblast cells invaginate through the primitive groove displacing the hypoblast laterally and forming the endoderm.
Which signalling molecules are important for gastrulation?
BMP, FGF and Wnt
What is the role of BMP in gastrulation?
Establishing the rostro-caudal axis
What do HOX genes control?
The cranio-caudal patterning of the body
When does primary neurulation occur?
3-4 weeks
What is primary neurulation?
Formation of the neural tube (plate, grooves and folds)
When does the primitive streak form?
Day 13
What is Hensen’s node?
The cranial end of the primitive streak
When does the notochord form?
Day 17
What releases sonic hedgehog?
The notochord
What forms the neural plate?
Notochord induces the primitive streak to form the neural plate
What causes the neural plate to form the median hinge and hence form neural groove?
SHH
When do the neural folds fuse to form the neural tube?
Day 22 - the prox 2/3 form the brain and distal 1/3 forms the spinal cord
Where does the neural tube start to close from?
The hindbrain (CCJ)
When does the anterior neuropore close?
24 days (forming the lamina terminalis)
When does the posterior end of the neural tube (at L1/2) close?
Day 26 - a problem at this stage causes neural tube defects and chiari malformations.
What is dysjunction?
Separation of cutaneous ectoderm from the neuroectoderm after neural tube formation. This forms intact dorsal skin.
What type of cells form the notochord?
Mesenchymal
What does the mesenchyme after dysjunction form?
Dura, neural arches and paraspinal muscles
What is the consequence of dysjunction occurring too early?
Mesenchyme can enter the neural tube and form lipomas / lipomyelomeningoceles
What is the consequence of a focal failure of dysjunction?
Ranging from a Dermal sinus (as the skin does not close over the top) to a myelomeningocele.
How do lipomyelomeningocoeles form?
The lipid and dura are mesenchyme. if dysjunction occurs too early before the neural tube has closed, then mesenchymal cells can enter the neural tube which form lipomas / meningoceles and combinations etc
When does secondary neurulation occur?
4-5 weeks
What is the consequence of failures of secondary neurulation?
Spinal dysraphism below L1/2
How do you know if a spinal dysraphism occurred due to primary or secondary neurulation failure?
If above L1/2 (encephalocoeles etc) then primary neurulation.
If below L1/2 then secondary neurulation.
What contributes to the branchial arches?
Neural crest cells
What conditions occur with the failure of ventral induction?
Holoprosencephaly, septo-optic dysplasia and dandy-walker malformation
What is holoprosencphaly?
Failure to form two hemispheres. Can be just between the frontal lobes (lobar), between frontal and parietal lobes (semi lobar) or fronto-parieto-occipital (alobar).
This is due to a failure of ventral induction.
What is septo-optic dysplasia?
Under development of the optic nerve, pituitary gland and absence of the septum pellucidum. (2 of the 3 need to be present to make the diagnosis). This is due to a failure of ventral induction.
When does neuronal proliferation and differentiation occur?
2-4 months. A failure at this stage causes AVMs and neurocutaneous syndromes.
When does cellular migration occur?
2-5 months with cells migrating from ventricular zones to the periphery (mantle layer). A problem at this stage causes callosal agenesis, schizencephaly and FCD / GM heterotopias.
What pathologies arise with a failure of cellular migration?
A problem at this stage causes callosal agenesis, schizencephaly and FCD / GM heterotopias.
When does neuronal organisation and myelination occur?
From the 5th month - proceeds from caudal to cephalad, dorsal to ventral and central to peripheral with sensory before motor.
When does myelination complete?
2 years
At birth, what are the normal GM and WM signals on MRI?
On T1 WM is dark and GM is light, this is the opposite in adults as the WM has not myelinated yet/
What is ventral induction?
Formation of 3 primary vesicles from the neural tube (prosencephalon, mesencephalon and rhombencephalon). Occurs between 5-10 weeks of gestation.
What do the prosencephalon, mesencephalon and rhombencephalon form?
Prosencephalon = Telencephalon and diencephalon
Mesencephalon = Mesencephalon
Rhombencephalon = Metencephalon and myelencephalon
What is the adult derivative of the telencephalon?
The cerebral hemispheres and lateral ventricles including the caudate, putamen, fornix, hippocampus, anterior commissure and corpus callosum.
What is the adult derivative of the diencephalon?
The thalamus and third ventricle including the GP, posterior pituitary, optic nerves and posterior commissure.
What is the adult derivative of the mesencephalon?
Midbrain and cerebral aqueduct
What is the adult derivative of the metencephalon?
Pons, cerebellum and upper 4th ventricle
What is the adult derivative of the myelencephalon?
The medullar and lower 4th ventricle
What does the germinal matrix form?
Neurons and glia from the 7th week of life. It involutes at the 30th week of life.
How does the corpus callosum form?
Genu > Body > Splenium > Rostrum. This is why partial agensis includes the splenium and rostrum.
When does the brainstem form?
Between 2-6 months
What does the alar plate of the brainstem contain?
Sensory nuclei
What does the basal plate of the brainstem contain?
Motor nuclei for developing cranial nerves
What are the three layers of the developing spinal cord?
Neuroepithelial
Mantle
Marginal
What does the neuroepitheal layer of the developing spinal cord form?
The ependyma that lines the central canal and also gives rise to neuroblasts that form the mantle and marginal layers.
What does the mantle layer (neuroblasts) form?
Gray matter of the spinal cord
What do the marginal layer (neuroblasts) of the spinal cord form?
White matter
What separates the alar (dorsal) and basal (ventral) plates?
The sulcus limitans
What forms the distal (caudal) spinal cord?
The caudal cell mass over weeks 4-8
What do neural crest cells form?
Leptomeninges, Schwann cells, sensory cranial nerves and DRGs, autonomic nervous system, adrenal medulla, APUD cells and melanocytes.
Where do the sympathetic nerves run in to reach the paravertebral ganglia?
White ramus communicans
Where does the conus lie at birth?
L3
What do the ectodermal placodes form (overlying the neural tube)?
The olfactory epithelium, cranial nerves 5, 7 and 9
What does the notochord remnant form?
Nucleus pulposus and the cell of origin of chordomas
What do dura, arachnoid and pia form from?
Dura = mesoderm
Arachnoid and pia = neuroectoderm
When does the metopic suture close?
1 year
When does the posterior fontanelle close?
2-3 months
When does the anterior fontanelle close?
2-3 years
At what stage of embryology does a defect cause diastematomyelia?
Gastrulation (as this results in two notochords and therefore two spinal cords)
What is dorsal induction also know as?
Primary neurulation and formation of the notochord
When does SHH cause the neural plate to hinge forming the neural tube?
After day 18
Where is the posterior neuropore?
S3
How does the filum terminale form embryologically?
Retrogressive differentiation which is an apoptotic process of the caudal cell mass followed by further differentiation
What occurs during ventral induction?
The differentiation of the 3 primary vesicles into the 5 secondary vesicles (weeks 4-5)
What are the brain flexures?
Cephalic flexure between diencephalon and mesencephalon
Cervical flexure between the myelencephalon and spinal cord forming a U-shape
Pontine / Dorsal flexure between the metencephalon and myelencephalon forming an M-shape
Where do the optic vesicles arise from?
The telencephalon forming the retina and optic nerves
What do the superior and inferior colliculi arise from?
The mesencephalon
What does the pineal gland develop from?
Diencephalon
What separates the mesencephalon from the rhombencephalon?
.The isthmus rhombencephalii
What shape is the pontine flexure?
Indents the rhombencephalon dorsally forming an M-shape
What does the cerebellum form from?
The Metencephalon
What does the foramen of Magendie form from?
Blake’s pouch (derived from the posterior membranous area)
What forms the roof of the 4th ventricle (tela choroidae) embryologically?
The AMA, choroid plexus and PMA (from superior to inferior)
What separates the anterior and posterior lobes of the cerebellum?
The primary fissure
What separates the posterior lobe from the flocculonodular lobe?
The posterolateral fissure
What are the deep nuclei of the cerebellum?
Dentate, Globose, Emboliform and Fastigial
What are the layers of the cerebellum?
(External granular layer - disappears 15 months post-natally)
Molecular layer - stellate and basket cells
Purkinje cell layer
Granular layer - Golgi cells, granule cells and parallel fibres
White matter - contains mossy fibres from brainstem nuclei, inferior olivary nucleus and deep cerebellar nuclei
All are GABA except granule cells which are glutamatergic!
What cell type is found within the mantle layer?
Post-mitotic young neurones
How does the cerebral cortex form?
Through successive waves of migration from the Ventricular zone.
The first wave of neurons forms the preplate and axons extending back form the intermediate zone.
The germinal matrix lies deep to the ventricular zone and takes over neurogenesis
The cortical layers are then laid down from deep to superficial
What controls the layering of neurones within the cortex?
Reelin (from Cajal-Retzius cells in the molecular layer)
In the cerebral cortex, what are granule cells?
Small inhibitory interneurons
When does the anterior commissure form?
Week 7 - connects the olfactory centers of the two hemispheres
What groove marks the junction of the alar (dorsal) and basal (ventral) plates?
The sulcus limitans
What forms the intermediolateral columns?
The posterior-most cells of the basal columns segregate and contain the sympathetic neurons between T1 and L2 and parasympathetic neurons in the sacrum (S2-4)
What are the general somatic efferents of the basal columns?
These lie most medially and include ocular and tongue muscle nuclei (CN3, 4, 6 and 12)
What are the special visceral (branchial efferents)?
Connective tissue derived from neural crest cells (CN 5, 7, 9 and 10) as well as 11 in the neck
Where does the CN4 (Trochlear nerve) leave the brainstem?
Below the inferior colliculus
Which cranial nerve nuclei have parasympathetic outflow?
CN3, 7, 9 and 10
What substance is found in high concentrations in the germinal matrix?
TPA (Tissue plasminogen activator) - may be why it is predisposed to haemorrhages
When does the anterior fontanelle close?
18 months
When do the sphenoid and mastoid fontanelles close?
Around 6 months
What do somites form from?
Para-axial mesoderm
What is a sclerotome?
The part of the somite that forms bone (skeletal tissue). The other parts of the somite are the myotome and dermatome.
What separates the sclerotome into cranial and caudal portions?
von Ebner’s fissure
What causes atlanto-occipital assimilation?
Failure of the 4th occipital sclerotome to split (normally the cranial part fuses with the occiput and the caudal part fuses with the top of the 1st cervical sclerotome to form C1).
Why do we have 8 cervical nerves and 7 vertebrae?
As the 1st cervical somite splits along von Erbner’s fissure to fuse with the 4th occipital sclerotome so the C1 nerve root exits above the C1 vertebra. The C8 root therefore exits below the C7 vertebra.
What does the PNS arise from embryologically?
Neural crest cells and ectodermal placodes
In what order do the components of spinal nerves arise?
General somatic efferents (motor)
General visceral efferents (motor)
General visceral afferents (sensory)
General somatic afferents (sensory)
*This occurs in a cranial to caudal direction
Which nerves have gray and white rami communicans?
All nerves have gray rami communicans.
White matter communicans are only present between T1 and L2 because they contain preganglionic sympathetic fibres that synapse with the sympathetic chain.
What do neurones in the cranial nerve sensory ganglia originate from?
Dual origin from neural crest cells and ectodermal placodes (nasal CN1, retinal CN2 and otic CN8 placodes). The remaining show a stratification with respect to their origin i.e. if the ganglion is close to the brain then it is derived from neural crest cells and if it is far then from the placode.
When do parasympathetic ganglia form?
4th week of life close to the organs they are destined to innervate
Where do parasympathetic preganglionic neurones reside?
Brainstem nuclei of CN3, CN7, CN9 and CN 10;
Intermediolateral columns of S2-4
What ganglia are associated with CN3, CN7 and CN9?
CN3 - Ciliary ganglion (neural crest cells arise from the mesencephalon)
CN7 - Sphenopalatine and Submandibular ganglia (neural crest cells arise form the rhombencephalon)
CN9 - Otic ganglion (neural crest cells arise from the rhombencephalon)
What is a somite?
Paraxial mesoderm that appears at day 20.
This gives rise to the bones and skeletal muscle of the trunk and limbs
When does the neural plate form?
Day 18
What do the pharyngeal arches consist of?
Mesoderm covered by ectoderm and lines on the inside by endoderm.
Each arch therefore has a skeletal element (from neural crest), striated muscle (from head mesoderm) innervated by the cranial nerve associated with that arch and an aortic arch artery.
When do the pharyngeal arches form?
From day 24-29 in a cranial to caudal fashion
What forms from the 1st pharyngeal arch?
*Mandibular*
Cranial nerve = V2/3,
Blood vessel = Maxillary branch of ECA
Muscles = mastication, anterior belly of digastic, mylohyoid, tensor tympani and tensor veli palatini
Bone = Maxilla, mandible, temporal bone, malleus, incus and sphenomandiular ligament.
What forms from the 2nd pharyngeal arch?
*Hyoid*
Nerve = CN7
Artery = Stapedial and Hyoid
Muscles = Facial muscles, Buccinator, Platysma, stapedius, Stylohyoid, posterior belly of digastric and auricularis
Bones = Stapes, styloid process, lesser horn and upper hyoid, stylohyoid ligament and Reichert’s cartilage
What forms from the 3rd pharyngeal arch?
CN 9
Artery = Common carotid and ICA
Muscle = Stylopharyngeus
Bone = Greater horn and lower body of hyoid, thymus and parathyroids
What forms from the 4th pharyngeal arch?
CN X - superior laryngeal nerve
Artery = On the Right the Subclavian A and on the Left the aortic arch
Muscle = Cricothyroid and soft palate muscles except tensor veli palatini (which is V3!)
Bone = Thyroid cartilage, superior parathyroids and epiglottic cartilage
What forms from the 6th pharyngeal arch?
CN X - recurrent laryngeal nerve
Blood vessels = On the right the pulmonary artery and on the left the pulmonary and ductus arteriosus
Muscle = Muscles of the larynx except form cricothyroid muscle
Bone = Cricoid, arytenoid, corniculate and cuneiform cartilages
An abnormality in which stage of embryology results in Sturge-Weber syndrome?
Neuronal proliferation
What condition is caused by an embryological failure of myelination?
Adrenoleukodystrophy
What condition is caused by an embryological failure of neural proliferation?
Neurocutaneous syndromes
Aqueductal stenosis
Micro and macrocephaly
What condition is caused by an embryological failure of segmental notochord formation?
Block vertebra
Segmental defects / spinal dysgenesis
Caudal regression syndrome
What condition is caused by an embryological failure of neuronal migration?
Lissencephaly / Polymicrogyria / pachygyria
Heteratopias
Schizencephaly
Agenesis of the corpus callosum
What condition occurs as a result of failure of both gastrulation and primary neurulation?
Hemimyelocele and hemimyelomeningocele
What are the main causes of neural tube defects?
Genetics
Nutrition (Folate / Vitamin A)
Drugs
What is spina bifida?
Defective closure of the neural arches as a result of a neural tube defect
What is myeloschisis?
Failure of closure of the caudal neuropore
What is meroancephaly?
Failure of the scalp, skull and brain to form resulting an exposed brainstem
Why do patients with Dandy Walker malformation get hydrocephalus?
As the foramena of magendie and luschka are blocked
What are the causes of hydrocephalus in neonates?
Germinal matrix haemorrhage
Neonatal infection
Brain tumours
When does the telecephalic vescile cleave to form two hemispheres?
37th day
What is the difference between a meningoencephalocele and a meningoencephalocystocele?
A meningoencephalocystocele also contains ventricles
Why do lipomyelomeningoceles cause Chiari 2 malformations?
- Traction theory - tethered cord pulls the posterior fossa contents into the canal
- Crowding theory - Small posterior fossa
- Unified theory - NTD causes persistent CSF leak
