Development of the Nervous System Flashcards
What are the main steps in the development of the nervous system?
Neural induction Neurulation Morphogenesis and patterning of neural tube Neurogenesis Neuronal migration Axon growth and pathfinding, and dendritic arborisation Synaptogenesis Gliogenesis/myelination
Define neural induction
Assigning neural potential to region of early embryo
Define neurulation
Forming rudimentary nervous system
Define neurogenesis
Production of neurons and glia from precursor cells
Define neuronal migration
Neurons move from sites of production to positions in mature brain
Makes space for new neurons
Define synaptogenesis
Making and refining synaptic connections
In what stages of nervous system development does apoptosis occur?
Neurogenesis Neuronal migration Axon growth and pathfinding, and dendritic arborisation Synaptogenesis Gliogenesis/myelination
Which part of the embryo acquires a neural fate?
Region of dorsal embryonic ectoderm = neural plate
What forms from the neural plate?
Entire CNS
What happens to the rest of the ectoderm?
Acquires epidermal fate
What determines epidermal fate?
Local bone morphogenetic protein (BMP) signalling
What is the organiser region of the neural plate, and what does it do?
Intermediate marginal zone
Cells underneath programmed to secrete inhibitors that stop cells above from becoming epidermis - block BMP signal
What is a neurula?
An embryo that has undergone neural induction
Happens at 3 weeks
What is neurulation?
Formation of the neural tube
How is the neural tube formed?
Neural plate cells become more columnar Elevation of neural folds Neural folds fuse in dorsal midline Neural tube pinches off from epidermis Occurs all the way along the embryo
What is the inside of the neural tube, and what does it contain?
Ventricle
Contains fluid
In which direction does the neural tube zip up?
Bidirectionally from initial point of closure
Where are the two points of closure of the neural tube?
Hindbrain-cervical boundary
Forebrain-midbrain boundary
What causes neural tube defects?
Failure of neural fold formation or closure
What doesn’t close in spina bifida?
Caudal neuropore
What doesn’t close in anencephaly?
Cranial neuropore
What is the role of folate thought to be?
Enhancing cellular competency
Where do neural crest cells develop?
At neural plate margin
When do neural crest cells migrate?
When dorsal margins of tube fuse
Where do neural crest cells migrate?
From dorsal to ventral side
What do neural crest cells give rise to?
Dorsal root ganglia Sympathetic ganglia Adrenal medulla Enteric NS ganglia Melanocytes Schwann cells Cartilage and bone of face and jaw
What happens after the neural tube closes?
Primary and secondary brain vesicles form
Describe the primary and secondary brain vesicles
Wall = neuroepithelium
Fluid-filled central cavity = ventricular system
What are the three vesicles that form at the rostral end of the neural tube?
Prosencephalon = forebrain Mesencephalon = midbrain Rhombencephalon = hindbrain
What does the prosencephalon split into?
Telencephalon
Diencephalon
What does the rhombencephalon split into?
Metencephalon
Myelencephalon
What does the telencephalon give rise to?
Olfactory bulb
Cerebral cortex
Hippocampus
Striatum/basal ganglia
What does the optic vesicle give rise to?
Retina
What does the diencephalon give rise to?
Thalamus
Hypothalamus
What does the mesencephalon give rise to?
Midbrain
What does the metencephalon give rise to?
Pons
Cerebellum
What does the myelencephalon give rise to?
Medulla
What provides the different positional cues for specifying cell fate?
Gradients of morphogens from patterning centres or organising regions
What induces the roof plate?
Overlying ectoderm
What does the roof plate secrete?
Dorsalising morphogens
What induces the floor plate?
Underlying notochord
What does the floor plate secrete?
Ventralising morphogen
What cell types are derived because of the roof plate?
Interneurons
Oligodendrocytes
What cell types are derived because of the floor plate?
Motor neurons
How many layers does the neuroepithelial lining of the brain vesicles have?
1
Why do the neuroepithelial cells in the vesicles appear multi-layered?
Nucleus develops at ventral end
Cell extends processes dorsally
Nucleus moves up and down processes with different phases of cell cycle
Called interkinetic nuclear migration
Where are neuroepithelial cells and what do they give rise to?
In ventricular zone
Self-replicate
Give rise to radial glia
Where are radial glia and what do they give rise to?
In ventricular zone
Self-replicate, and give rise to intermediate progenitors and astrocytes = asymmetrical cell divisions
Where are the intermediate progenitors and what do they give rise to
In sub-ventricular zone
Give rise to neurons
What are radial glial cells?
Neural stem cells
What are symmetric divisions?
Produce two identical daughter cells
Expand neuroepithelial progenitor pool early
Give rise to two neurons late
What are asymmetric divisions?
Produce two different daughter cells
Radial glia divide and produce a radial glial cell and a differentiated neuron
What is the structural role of radial glia?
Provide scaffold for radial migration of neuron progeny
Where do the neuronal progeny of radial glia migrate to?
Away from ventricular zone towards pial surface of brain
What is the order of cortical layer formation?
Earliest form preplate
Preplate splits into marginal zone and subplate when first wave of cortical plate neurons arrive
Neurons of cortical plate assemble into layers II-VI in inside-out way
- Deepest layers first
Where are the stem cells of the adult brain?
At ventricle
What do stem cells of the adult brain produce?
Neurons for olfactory bulb
Where are cortical interneurons produced?
Basal forebrain
Along what do olfactory bulb neuroblasts migrate?
Rostral migratory stream
Where do cerebellar granule cell precursors originate>
Rhombic lip
What are some neuronal migration disorders?
Schizencephaly = clefts in brain Lissencephaly = smooth brain Agyria = lack of folds pachygyria = thick folds Polymicrogyria/microgyria = many/small folds Neuronal heterotopia = other place, including band heterotopia = double cortex Agenesis of corpus callosum Agenesis of cranial nerves
What are some symptoms of neuronal migration disorders?
Vary
Poor muscle tone and motor function
Seizures
Developmental delay and impaired cognitive development
Failure to grow and thrive, and difficulties with feeding
Smaller than normal head
How is grey matter heterotopia formed?
Neurons fail to migrate from ventricle, or migrate halfway to cortical plate
What is the result of grey matter heterotopia?
Disorganised patches or bands of misplaced neurons
What is band heterotopia caused by?
DCX mutation on X chromosome
What happens in band heterotopia?
Neurons that fail to migrate accumulate below layer of white matter
How does a cobblestone cortex occur?
Neurons overshoot cortical plate and reside in layer I
Are neurogenesis and gliogenesis controlled by the same transcriptional programs?
No
They also inhibit each other
What occurs first: neurogenesis or gliogenesis?
Neurogenesis
What proportion of neurons are pyramidal?
80%
What do pyramidal neurons do?
Excitatory long-range projection neurons
Axons project to other cortical hemisphere or sub-cortical targets like spinal cord
What proportion of neurons are interneurons?
20%
What do interneurons do?
Mainly locally-projecting inhibitory neurons
Modulate cortical excitatory output
How does the dendritic arbor develop?
Basic plan genetically specified Growth and branching influenced by environmental factors - Local signals - Contact-dependent - Diffusible cues - Active synapses
How do dendrites and axons grow?
Repulsion of outgrowing axon
Attraction of apical dendrite
Elongation/retraction and branching of apical/basal dendrites
Activity-dependent spine stabilisation
What controls the extent of the dendritic arbor?
Growth factors
Where does axon growth happen?
At the very motile tip of the neurite = growth cone
What do actin filaments do in growth cones?
Regulate shape and directed growth of growth cone
Where are these actin filaments in the growth cone?
Filopodia
What do microtubules do in the growth cone?
Provide structural support to axon shaft
Essential for axon extension
Help push growth cone forward
When do microtubules grow in?
After actin filaments stabilise
What sort of environmental guidance cues steer growth cones?
Gradient of long-range repellent and attraction
Contact adhesion and repulsion
Growth cone senses and integrates signals
What is the corpus callosum?
Largest fibre tract in brain
Formed by axons projecting to opposite hemisphere
What do axon guidance defects result in?
Complete or partial failure of corpus callosum to form
What are the symptoms of agenesis of the corpus callosum?
Variable severity Sensory and motor deficits including: - Vision impairments - Low muscle tone - Poor muscle coordination - Delays in motor milestones Cognitive disabilities; eg in: - Complex problem solving - Missing subtle social cues
When do gyri and sulci start to develop?
Seven months of gestation
What processes in brain development continue or happen after birth?
Axonal and dendritic outgrowth
Synapse formation
Myelination
What is the relative rate of development of excitatory and inhibitory synapses?
Excitatory synapses peak a lot earlier than inhibitory synapses develop
What does refinement of of synapses involve?
Connections originally overproduced
Performance improved by adjusting number, boundaries, and strength of connections through competitive process
Eg: poly- to mono-innervation at developing neuromuscular junction
