Neuroembryology Flashcards
Spina bifida
-the vertebral arches and/or spinal cord fail to form completely
-Spina bifida occulta: only the vertebral arch is defective
*skin may be covered with a tuft of hair
*May occur in up to 10% of live births
Spina bifida cystica:
-Spina bifida w/ meningocele:
*meninges protrude through vertebral arch and skin
-Spina bifida w/ meningomyelocele:
*meninges & neural tissue protrude thru vertebral arch & skin
-Rachischisis: neural folds fail to elevate or close
*forming an exposed flattened mass of neural tissue.
Neurulation
- 3rd week
- ectoderm over notochord thickens forming neural plate.
- Lateral edges of neural plate elevate to form neural folds.
- The depression b/t the neural folds is the neural groove.
- The folds and the groove together comprise the neurectoderm.
- Folds approach & meet each other dorsally in the midline
- create a cylinder: the neural tube.
- Cells in apex of the neural fold meet
- separate from the neural tube to form the neural crest.
- Meeting of the neural folds occurs first in the occipital region
- proceeds cranially and caudally.
- cranial end (anterior or cranial neuropore) closes on 25th day
- Lamina terminalis: site of closure of the cranial neuropore.
- The caudal neuropore closes on about day 28.
- Rostral portion of tube enlarges to become primordial brain
- caudal portions remain narrow and become the spinal cord.
Cranial NTDs
- defects in the formation of skull bones and/or brain
- Meningocele: meninges bulge through an occipital bone defect
- Meningoencephalocele: meninges & brain tissue bulge through an occipital bone defect
- Meningohydroencephalocele: meninges, brain tissue and part of the ventricular system bulge through an occipital bone defect
- Anencephaly: failure of anterior neuropore closure with most of brain and skull roof absent
Adult structures that are derived from neural crest
- Neural crest cells migrate from dorsal surface of tube along well-defined pathways and give rise to:
- pigment cells
- dorsal root ganglia (primary sensory neurons) and some cranial nerve sensory ganglia
- schwann cells and satellite cells
- sympathetic and parasympathetic ganglia
- adrenal medulla chromaffin cells
- C-cells of the thyroid gland
- dentin
- facial skeleton.
Origin of Neurons
- neuroepithelial cells comprise ventricular zone of neural tube
- neuroepithelial cells give rise to primitive neuroblasts.
- neuroblasts in a zone around ventricular: the mantle layer
- In mantle layer, neuroblasts differentiate into neurons
- Neurons lose ability to divide
- transition from unipolar neuroblasts to multipolar neuron.
- Neurogenesis is mostly complete by six months
- Except cerebellum: cell proliferation thru the 1st postnatal year.
- neuroblasts migrate guided by radial glial fibers.
- Migration of neurons until before birth in cerebral cortex
- up to a year after birth in the cerebellum.
- Axons sprout from developing neuroblasts
- forms layer of white matter surrounding the mantle layer
- referred to as the marginal zone.
Origin of Glia
- After neuroblast production ceased, the neuroepithelial cells of the ventricular zone give rise to glioblasts
- glioblasts differentiate into the macroglia
- astrocytes and oligodendrocytes
- Microglia are thought to arise from the mononuclear cell line.
- remaining neuroepithelial cells differentiate into ependymal cells
- line the central canal and the ventricles of the brain.
- These cells will produce and circulate CSF.
Explain why the spinal cord ends at the L1 vertebral level in adults
- Before 3rd embryonic month, spinal cord extends the length of the vertebral column.
- Vertebral column grows faster than the cord.
- At Birth, the cord extends to L3.
- Adult cord ends b/t the L1 and L2 b/c the vertebral column grows faster
- Cauda equina extends further down the cord.
Differentiation of the Spinal Cord: Basal Plate
- The mantle layer develops dorsal and ventral thickenings,
- the alar and basal plates
- Sulcus limitans: longitudinal grove in wall of the central canal
- junction b/t alar and basal plates.
- The basal plates become the adult ventral horns.
- Basal plate derivatives associated w/ motor function.
- Includes:
- lower motor neurons whose axons innervate skeletal muscle
- preganglionic autonomic neurons.
Differentiation of the Spinal Cord: Alar Plate
- The alar plates become the adult dorsal horns.
- Alar plate derivatives associated w/ sensory function.
- Includes Sensory relay neurons of the spinal cord
- receive input from 1˚ afferent sensory neurons
- project to higher brain areas).
Development of the cerebellum
- Developing metencephalon
- Dorsolateral part of alar plate expands to form the rhombic lips
- rhombic lips bulge into 4th ventricle, separated by thin roof plate.
- expanding rhombic lips overgrow roof plate & meet in midline.
- Vermis: midline portion of the cerebellum,
- Develops from rhombic lip site of fusion
- Cerebellar hemispheres develop lateral to the vermis.
- Rapid growth of surface layers creates an extensive foliation.
- Rhombic lip structures- extensive connections w/ cerebellum
- inferior olive, pontine nuclei
- Cerebellar neurogenesis continues up to one year postnatally,
- DNA-blocking antiviral drugs may cause cerebellar damage
- Don’t gives these drugs to neonates
- Arnold-Chiari malformation
- Cerebellar herniation is frequent in congenital hypoplasia of the posterior cranial fossa
3 Regions of Primordial Brain
- The expanded rostral portion of the neural tube forms three hollow vesicles (enlargements):
- Prosencephalon (forebrain)
- Mesencephalon (midbrain)
- Rhombencephalon (hindbrain)
Derivatives of the Diencephalon
- Arises from Prosencephalon
- Diencephalon has thickened lateral walls derived mostly from alar plate and a thin roof plate
- Derivatives include the:
- thalamus
- hypothalamus
- subthalamic nucleus
- epithalamus and pineal gland
- choroid plexus of the 3rd ventricle
- globus pallidus
- infundibulum and neurohypophysis
Derivatives of Telencephalon
- Cerebral hemispheres: originate the telencephalic vesicles
- The cavities within these vesicles become the lateral ventricles.
- The basal, ventrolateral region gives rise to the amygdala, caudate & putamen
- become separated by axons that grow through this area to form the internal capsule
- Expanding telencephalic vesicle grows in a C-shape
- brings the temporal lobe to ventral position (covers lateral diencephalon and midbrain)
- Caudate, lateral ventricle & hippocampal/fornix system are C-shaped b/c of this growth pattern
- Cortex lateral to the lentiform nucleus is overgrown by adjacent frontal, temporal & parietal lobes
- forms the insula.
- Anterior commissure and corpus callosum appear in the region of lamina terminalis.
- The anterior commissure maintains this position
- Corpus callosum grows in anterior/dorsal/posterior sequence to give it a hook-shape in the adult.
Derivatives of Metencephalon
(pons and cerebellum)
Derivatives of Myelencephalon
medulla
General Characteristics of Pharyngeal Arches
- There are five pharyngeal arches, numbered 1, 2, 3, 4 and 6
- (there is no recognized arch 5).
- Each arch contains
- a skeletal element (derived from neural crest or mesoderm)
- a muscular component (derived from mesoderm)
- a cranial nerve
- an aortic arch.
- Cranio-caudal patterning of the pharyngeal arches is regulated by homeobox (HOX) genes.
- The first arch forms two processes, maxillary and mandibular.
Aortic Arch Derivatives of Each Pharyngeal Arch
- None
- None
- Common Carotid Artery
- Subclavian Artery (Right) and Aortic Arch (Left)
- Portions of pulmonary artery
Skeletal Derivatives of Each Pharyngeal Arch
- Sphenoid, incus, maxilla, zygoma, squamous temporal, malleus, mandible, sphenomandibular ligament
- Stapes, Styloid, Stylohyoid ligament, upper hyoid bone
- Lower hyoid bone
- Laryngeal cartilages
- Laryngeal cartilages
Muscular Derivatives of Each Pharyngeal Arch
- Muscles of Mastication, Mylohyoid, Anterior Digastric, tensor tempani, tensor veli palatinin
- Muscles of facial expression, stapedius, stylohyoid, posterior digastric
- Stylopharengeus
- Muscles of palate except tensor veli palatini, muscles of pharynx except Stylopharengeus, crichothyroid
- All laryngeal muscles except crichothyroid
Associated Cranial Nerve for Each Pharyngeal Arch
- V3
- VII
- IX
- X
- X
Pharyngeal Clefts Derivatives
-Only 1st pharyngeal cleft persists in recognizable form in adult:
*gives rise to the external acoustic meatus.
-Tissue around 1st cleft, from both the 1st & 2nd arches
*forms the auricle.
-ectoderm & endoderm (w/ mesoderm) b/t 1st pouch & 1st cleft
*form the eardrum (tympanic membrane).
Clefts 2, 3 and 4: overgrown by tissue from the 2nd arch
*creating a cervical sinus.
*Cervical sinus normally closed over & obliterated,
-may occasionally persist as a cyst
*opening to skin at the anterior border of the SCM as a sinus
*Rarely, perforates to pharynx, & creates a cervical fistula
connecting the skin of the neck to the area of the palatine tonsil.
Derivatives of the pouches
Pouch and respective derivative
1 Middle ear cavity and the auditory tube
2 Tonsillar crypts
3 Inferior parathyroids, thymus
4 Superior parathyroids
5 C cells (originally from neural crest) of the thyroid gland
Formation of tongue from pharyngeal arches
- Anterior floor of the pharynx: related to the first arch
- two lateral lingual swellings & a midline tuberculum impar appear
- Lateral swellings overgrow tuberculum impar
- form the anterior 2/3 of the tongue.
- The posterior 1/3 of tongue derives from the copula
- tissue from the 2nd, 3rd & 4th arches (mostly third).
- Portion of the floor of the pharynx derived from the 2nd arch
- probably overgrown by the 3rd arch.
- Anterior 2/3 of tongue receives general sensory innervation from nerve of the 1st arch, CN V3
- Posterior 1/3 receives general & special sensory innervation from nerve of the 3rd arch, CN IX.
- Occipital somites invade tongue & give rise to skeletal muscles
- As they migrate, occipital myotomes carry CN XII with them
Migration of the Thyroid
-Epithelial proliferation develops at midline of floor of the pharynx
*junction of 1st & 2nd arches
*will become the thyroid gland.
-The thyroid descends to reach its adult location.
-foramen cecum is the thyroid’s original location.
As it descends, the thyroglossal duct connects the developing thyroid to its site of origin.
*Normally this duct will degenerate.
-Cysts and/or ectopic thyroid tissue can develop anywhere along the track of the descent of the thyroid gland.
Development of the Face
- The face begins as five prominences:
- one frontonasal, two maxillary and two mandibular.
- The latter two are derived from the first pharyngeal arch.
- Frontonasal prominence: future forehead & midline of upper face.
- Paired ectodermal nasal placodes form near the inferior margin of the frontonasal prominence.
- Each placode creates a depression in the underlying mesoderm.
- Tissue around placode divides into medial & lateral nasal prominence
- also called nasomedial and nasolateral prominences
- LT & RT mandibular prominences merge: form a single lower jaw.
- 2 medial nasal prominences merge to form:
- bridge of nose
- the nasal septum
- philtrum of the lip
- front of the hard palate & upper incisors.
- Maxillary prominence merge w/ ipsilateral lateral & medial nasal prominences.
- nasolacrimal groove forms b/t each maxillary prominence & its adjacent lateral nasal prominence.
- grooves deepen & close over to form the nasolacrimal ducts.
- Lateral parts of maxillary & mandibular prominences join each other at corners of the future mouth
- narrow it and form the cheeks.
Cleft Lip
- Failure of a maxillary prominence to fuse w/ adjacent medial nasal prominence
- results in unilateral “hare lip”.
Cleft Face
- Failure of a maxillary prominence to fuse w/ the lateral and medial nasal prominences
- results in a cleft face.
Treacher-Collins syndrome
- Underdeveloped zygomatic and mandibular bones in
- downslanting palpebral fissures and malformed external ears
Pierre-Robin sequence
- similar to Treacher-Collins affecting first arch structures
- usually presents with small jaw, cleft palate and a posteriorly placed tongue.
Development of the Nasal Cavity and Palate
- nasal placodes continue to indent the underlying tissue
- creates the nasal pits.
- tissue b/t the deepening nasal pits & oral cavity breaks down
- creates a common oral and nasal cavity.
- Fused medial nasal prominences (intermaxillary segment) send horizontal shelf posteriorly
- Primary palate will become anterior part of the definitive palate.
- Downgrowth from the frontonasal and fused medial nasal prominences forms the nasal septum.
- The maxillary prominences develop extensions that are oriented downward, straddling the tongue.
- Tongue obtains lower position w/ forward growth of mandible & maxillary prominences
- swing up & meet each other, the intermaxillary segment & the nasal septum.
Cleft Palate
-Failure of maxillary prominences, intermaxillary segment & nasal septum to fuse
