neuroembryology/case 1 Flashcards
what is neurulation?
process of formation of the NS during neural plate formation: folding and closure of neural plate
what is circulatory formation?
formation of synapse and connections between neurones and muscle cells
what is the difference between the brainstem/spinal cord and cerebral cortex development?
brainstem/spinal cord are hard wired whereas the cerebral cortex is plastic:
- notochord does not control the development of forebrain
- genetics:
- Hox gene for brainstem/spinal cord
- EMX and Otx for forebrain - timing
- fluid system
- brainstem/spinal cord don’t produce CSF
What are the 4 steps of the development of the NS
- induction of the neural plate
- patterning of the CNS
- neurogenesis (neuronal differentiation)
- wiring of the brain to establish functional neuronal circuits
Which stem cell develops into the NS?
ectoderm
When does induction of the neural tube start?
3rd-4th week
What happens with the induction of the neural tube?
- dorsal midline ectoderm undergoes thickening –> neural plate
- lateral margins become elevated to become neural folds and middle depression –> neural groove
- neural folds become opposed –> neural tube
- cells from neural folds becomes separate and form neural crest
when does the anterior neuropore close and what happens if there is failure to close?
day 25
anencephaly
when does the posterior neuropore close and what happens if there is failure to close?
day 28
spina bifida
which part of the neural tube do the 1. rostal part 2. caudal part 3. central cavity 4. neural crest become?
- brain
- spinal cord
- central canal of spinal cord and ventricles of the brain
- sensor ganglia of spinal, cranial nerves and autonomic ganglia
what is a morphogen?
signalling molecule (secreted proteins) that acts directly on cells to produce specific cellular responses depending on its local concentration (dose dependent)
What is the dorsoventral axis set up by?
cross dose-dependent gradient of morphogens:
- ventral region (floor plate): secretion of SHH (by notochord)
- dorsal region (roof plate): secretion of BMP initially and TGF-beta proteins (transforming growth factor beta)
What is the sulcus limitans?
longitudinal groove that appears on the lateral wall of the embryonic spinal cord and caudal part of the brain (in spinal cord separates alar and basal plates
what is the alar plate?
dorsal cell groupings: predominant sensory functions
what is the basal plate?
ventral cell groupings: predominant motor functions
What are the cell groupings within the alar plates?
from dorsal to ventral:
- special somatic afferent
- general somatic afferent
- special visceral afferent
- general visceral afferent
What are the cell groupings within the basal plates?
from dorsal to ventral:
- general visceral efferent
- brachial efferent
- somatic efferent
What does SHH stand for?
Sonic hedgehog
What does BMP stand for?
Bone morphogenic protein
What is the anteroposterior axis set up by?
expressed by SGF gradient (secretory growth factor):
-FGFs (fibroblast growth factor) expressed in gradient from posterior end
-retinoic acid: expressed from anterior end
+ homeotic genes
By when do the 3 primary brain vesicles develop?
5th week
By when do the 5 secondly brain vesicles develop?
7th week
What are the three primary brain vesicles?
- prosencephalon (forebrain)
- mesencephalon (midbrain)
- rhombencephalon (hindbrain)
What are the five secondary brain vesicles?
- telencephalon (cerebral hemisphere)
- diencephalon (thalamus)
- mesencephalon (midbrain)
- metencephalon (pons, cerebellum)
- myelencephalon (medulla oblongata)
What are the flexures of the neuraxis?
- midbrain/cephalic flexure: junction of forebrain to midbrain
- cervical flexure: between brain and spinal cord
- pontine flexure: between mesencephalon and myelencephalon
What causes the splitting of the two hemispheres of the brain?
SHH
What are the characteristics of neuroprogenitor cells?
- polarised (at apical surface due to apical complex)
- proliferate by diving at apical surface (symmetric proliferative
what does wiring of the NS?
functional circuits to respond to stimulus
what are pioneer neurons?
an axon that lays down growing paths for the other axons of the same neuron to follow
What radar do pioneer neurons follow?
the SHH radar (from ventral to dorsal and from posterior to anterior): neurons move from dorsal to frontal regions and then move up towards brain: the neutrons are first attracted then repulsed by SHH
What are causes for neurodevelopment defect?
- genetic
- metabolic/immune disorders
- environmental
- accidents (trauma/infections)
axons form synapses through molecular and activity dependent mechanisms, what happens to neurons that do not form synapses?
dynamic process of elimination: refine the circuit
What are the three most common of neural tube defects?
spina bifida
anencephaly
chiari malformations
What are the three type of spina bifida?
- spina bifida occulta
- meningocele
- myelomeningocele
What are the characteristics of spina bifida occulta? (symptoms, pathophysiology, treatment)
- “hidden”: frequently no symptoms, small patch of hair, dimple, darker-coloured skin or selling in the skin over affected vertebrae due to growth factors
- small opening in the vertebrae of spinal cord but no damage to the spinal cord itself
- no treatment needed
What are the characteristics of meningocele? (symptoms, pathophysiology, treatment)
- rarest type
- spine is open and meningocele (sac) comes through containing meninges and spinal fluid: cord is not affected
- surgery
- mild disabilities
What are the characteristics of myelomeningocele? (symptoms, pathophysiology, treatment)
- open spina bifida: meninges and nerves are out
- danger of infections
- can lead to leg paralysis, difficulty in urination and bowel movement (sensory and motor neurone affected) + leg and foot deformities
- hydrocephalus due to Arnold Chiari 2 malformation (cerebellum and brainstem tissue slip down into foramen magnum) + collection of too much CSF in brain, can’t drain normally causing pressure to build up leading to seizures, problems with NS or mental retardation
- treatment: prenatal/postnatal surgery, urinary cauterisation, wheelchair or crutches, shunts for hydrocephalus (to drain fluid)
What is the aetiology of spina bifida?
- genetic and environmental
- 30% of neural tube defects are sensitive to folate acid: 1st trimester vey important (until W4)
- ectoderm form ridges that become neural tube: fails to close properly; absence of vertebral arches due to failure of mesoderm to organise over region of defect
What are risk factors for spina bifida?
-obesity
-poorly controlled diabetes
-antiseizure medicine
-folic acid (B9) deficiency
-low SES
-low parity
(more educated women are less likely to have spina bifida but women that work have higher chance of having a baby with spina bifida)
How do you diagnose spina bifida?
- at 16-18 weeks: increase AFP (alpha fetoprotein) in mothers serum (leakage of APF into amniotic fluid due to missing skin around foetus spine)
- HCG, inhibiting A, oestriol (blood tests)
- ultrasound: lemon test (anencephaly detectable at week 12 and SB at week 16-20
- amniocentesis (AFP and assay of neuronal acetylcholinesterase)
What is the Lemon/Banana sign?
- ultrasound features of the Arnold Chiari malformations in foetuses with open neural tube defects
- banana sign: shape of cerebellum (caudal displacement)
- lemon sign: lemon shaped head (scalloping of frontal bone)
What are the different types of Arnold-Chiari malformations?
- type 1: acquired (symptoms: headaches)
- type 2: associated with lumbrosacral myelomeningocele (clinical features: paralysis below spinal defect)
- type 3: downwards displacement of cerebellum into posterior encephalocele (extremely rare and generally incompatible with life)
- type 4:cerebellar hypoplasia
What is the Arnold-Chari malformation?
- congenital disorders: distortion of base of skull and protrusion of the lower brainstem and parts of cerebellum through foramen magnum
- may be associated with hydrocephalus and springomyelia (cyst formation in spinal cord)
what are the different cranial markers for spinal bifida?
- lemon sign
- ventriculomegaly
- microcephaly (smaller head than normal)
- obliteration of the cisterna magna with an absent cerebellum
- abnormal anterior curvature of the cerebellum
What is the epidemiology of neural tube defects?
1:500 global
What is the difference between anencephaly (1), encephalocele (2)?
- absence of a major portion of the brain, skull and scalp
2. sac-like protrusions of the brain and the membranes that cover it through openings in the skull
what does teratogenicity mean?
property of producing congenital malformations
How do anti epileptic drugs cause teratogenicity?
causes malabsorption of folic acid in the intestine
What does folic acid do?
(DNA synthesis/repair
cell division
neurodevelopment)
-folic acid is converted to THF (tetrahydrofolate) which plays a role in transfer of 1-carbon units to essential substrates involved in synthesis of DNA and RNA
What is the notochord?
- required for patterning surrounding tissues (signal secreted by notochord is SHH)
- mechanical influence of the folding in early embryo
how are neuroblasts generated?
asymmetrical devision: (one daughter cell becomes post-mitotic neuroblast and the other re-enters the cell cycle)
