Development of Nervous System Flashcards
What is gastrulation
- Conversion of bilaminar embryo into trilaminar embryo
- Migration of superficial epiblast cells (totipotent) interiorly creates a third layer
What are the steps involved in gastrulation
- Epiblast cells migrate to primitive streak, form longitudinal axis
- Cells push through primitive groove and form mesoderm
- Mesoderm spreads between epipvastic and hypoblastic layers of embryonic disc
- Areas where embryonic mesoderm cells are absent form cloacal and oral membrane
What is organogenesis
- Formation of body organs and organ systems
- Endoderm, mesoderm and ectoderm
What does the endoderm form
- Inner layer from hypoblast
- GI tract / associated glands
- Lungs
- Urinary tract / mucosae
- Thyroid cells
- Pancreatic cells
What does the mesoderm form
- Middle layer, somites paired mesodermal blocks
- Muscles
- Bones
- Circulatory system
- Tubule cells of kidney
What does the ectoderm form
- Outer layer, from epiblast
- Neurulation causes differentiation to brain and spinal cord
- NS
- Skin / epidermis
- Hair
What are the phases of neurodevelopment (4)
- Neural plate formation and induction (delineation of ectoderm cells)
- Neural proliferation, migration and aggregation
- Axon growth and synapse formation
- Cell death and synapse rearrangement
What occurs in neurulation (2)
- Neural plate develops neural folds to form neural tube
- Bending: 3 hinge points, median hinge point (over pre-chordal plate) and paired dorsolateral hinges
- Folding: Rotation of plate around hinge points, elevation (folding MHP) and conversion (folding DLHP)
What are the steps in neural tube formation (neurulation)
- Cells migrate cranially from primitive node to form notochord
- Notochord induces ectodermal cells to elevate and thicken, forming neural plate
- Folds fuse to to elevation of hinge points and form neural tube (closes from middle outwards) with neural crest above
- PNS develops from neural crest
- Placodes give rise to ears and nose
What is BMP signalling
- Bone morphogenetic proteins
- Potent epidermalising agent
- Inhibition is required for neural crest induction and signalling
- Initially BMP promotes formation of non-neural ectoderm
- Inhibition is required to establish primitive neural tissue (neuroectoderm)
What is Wnt signalling
- Secreted signalling proteins
- Promote cell cycle progression in stem and progenitor cells
- Associated with BMP signal activation in dorsal spinal cord
What is a neural tube defect
- Failure of neural tube to close (1 in 500)
- Tube closes from the middle and extends anteriors / posteriorly
What are examples of neural tube defects
- Anencephaly (defect in anterior closure)
- Spina bifida (defect in posterior closure, leg weakness, orthopaedic abnormalities, paralysis)
Why is folate important in pregnancy
- Folate is a water soluble vitamin that is present in food (green leafy vegetables)
- Important in the synthesis of DNA, DNA repair and methylation of DNA
- Prevents NTD births among most women who have previously had NTD affected births
- Folate supplements of 0.4-5 mg per day suggested
What occurs during neural proliferation, migration and differentiation (2)
- Proliferation: Swellings of anterior brain become forebrain, midbrain and hindbrain, daughter cells become fixed
- Migration: Slow movement guided by radial glia, soma and immature axons, aggregation occurs once complete
- Differentiation: Cells location determines differentiation (function / precise connections), active
What occurs during axonal growth (3)
- Once migration is complete and structures have formed (aggregation)
- Axons and dendrites grow to their mature size / shape
- Growth cones guide axons with long range (chemo repulsion / attraction) and short range (contact repulsion / attraction) cues
- Fasciculation (grouping of axons)
What occurs during axonal synaptogenesis (3)
- Axons (with growth cones) and dendrites form synapse with other neurons or tissue (muscle)
- Formation of synapses depends on presence of glial cells (especially radial / astrocytes)
Describe what happens with neuronal death and apoptosis (4)
- Controlled cell death
- Responsible for shaping organs and tissue
- Unwanted cells are removed (evolution)
- 40-75% of neurons die after migration
- Death due to neurotrophin signals, lack of signals causes apoptosis (extrinsic)
- Survival or neurite out growth)
What postnatal growth occurs in the CNS
- Synaptogenesis
- Increased dendritic branches
- Myelination (prefrontal cortex continues into adolescence)
- Increased recovery from injury in adolescence in comparison to an adult
What is foetal alcohol syndrome
- Alcohol inhibits all stages of brain development
- Promotes neuronal cell death
- Infant show problems with sleep, muscle tone and sensory information processing
- Children are hyperactive, poorly coordinated
- Adolescent / adult show poor judgment, problems with arithmetic and frustration/anger
What are the primary brain vesicles
- Develop at rostral (anterior) end of neural tube
- Forebrain / Prosencephalon: Telencephalon and diencephalon
- Midbrain / mesencephalon
- Hindbrain / Rhombencephalon: Metencephalon and myelencephalon
What is the forebrain
- Prosencephalon
- Conscious awareness and cognition, voluntary actions and movement
- Sensory and motor connections
- Telencephalon (cerebrum, cerebral cortex)
- Diencephalon (thalamus, hypothalamus, epithalamus)
- Secondary vesicles sprout either side (hemispheres), optic vesicles invaginate, remaining is diencephalon
What is the midbrain
- Mesencephalon
- Relay and processing of information from cerebral cortex to spinal cord
- Tectum (dorsal surface, superior / inferior colliculus), cerebral aqueduct, tegmentum (red nucleus / substantia nigra)
What is the hindbrain
- Rhombencephalon
- Coordinates respiratory rhythm, motor activity, sleep and wakefulness
- Rostral portion becomes metencephalon and myelencephalon (medulla oblongata / brain stem)
- Pons: Bridge from cerebellum to medulla
- Medulla: Sensory and motor functions
- Cerebellum: Movement, body’s position in space, best sequence of muscle contraction
What are specialities of the human brain
- Olfactory Bulbs: Smaller
- Brain Flexures: Cervical (brain stem / spinal cord), midbrain (pushes mesencephalon up) and pontine (4th ventricle)
- Convolutions: Increased SA, gyri / sulci, massive expansion
What is hydrocephalus
- Enlargement of ventricles due to increased CSF
- Leads to compression atrophy
- Congenital (ventricular abnormality) or acquired (fibrous adhesion blockage)
- Increased ICP, weakness, reduced coordination, dementia, brain damage
What is differentiation of the spinal cord
- Proliferation occurs in 2 zones
- Characteristic butterfly shape of gray matter
- Lateral walls of tube thicken
What are 3 important aspects of a differentiated spinal cord
- Sulcus Limitans: Separates gray matter into dorsal alar and ventral basal plates
- Alar Plate: Neuronal cell bodies, dorsal gray matter, receive and relay input
- Basal Plate: Cell bodies form ventral matter, motor fibres to skeletal muscle, ventral roots
When does development of PNS occur
- Cells from neural crest migrate pat neighbouring somites to numerous locations
- Form dorsal root ganglia (sensory), sympathetic and parasympathetic ganglia
What is SHH
- Sonic Hedgehog
- Controls important developmental processes
- Secreted from the notochord and floor plate
- Promotes proliferation, downstream activation of Gli3
- Mutations: Cause of severe holoprosencephaly (HPE), lead to cyclopia, failure of axial midline to form