Overview of CNS development Flashcards
What is morphogenesis?
System level changes - change in size and shape during the embryonic development of the nervous system
What is cell differentiation?
Cellular level changes: Process over time whereby an initially homogeneous cell population gives rise to different cell types.
What are the developmental stages of the embryo, from day 0 to birth?
Day 0: Fertilisation and cleavage of the egg
- egg cleaves and forms a blastocyst
Day 7 (one week): Implantation of blastocyst into uterine wall - formation of embryonic disk - with 2 layers: epiblast and hypoblast
Day 14 (two weeks): Gastrulation - transformation of the 2-layered disk into 3 'germ' layers: ectoderm, mesoderm, endoderm - give rise to all tissues
Day 21 (3 weeks): Neurulation - creation of the embryonic nervous system from the ectoderm (neural induction)
Week 4-5: Tailbud stage
- embryo recognisable with a head and tail
Week 4-8: Embryonic period
- organogenesis occurs
- main tissue and organ systems develop
- major body features develop
3rd month - birth: Foetal period
- maturation of tissues and organs
- rapid growth of the body
- cell proliferation (important for the brain)
What is neural induction?
In the process of neurulation (at 3 weeks of embryo):
- Ectoderm is induced by the underlying mesoderm to become neural tissue
Morphogenic and genetic changes transform section of the ectoderm into the neural tube
- Ectoderm develops into the neural tube
What happens during early neurulation (19-20 days)?
At 19-20 days
> Embryo is composed of 3 germ layers
- ectoderm on top
- mesoderm in the middle - includes the notochord
- endoderm
> Neural plate of the ectoderm transforms into neural folds
> Somites form in the mesoderm, and give rise to axial muscles
> Lateral regions of embryo give rise to the epidermis of the skin
> Medial part of embryo give rise to the nervous system
What happens during late neurulation (22-23 days)?
At 22-23 days
1. Neural folds of the ectoderm approach each other
- Somites in the mesoderm expand
- Neural tube closes and becomes separated
- one region of neural tube has started to fuse, usually neck region
- neural tube closes at the anterior and posterior ends - Ectoderm layer has formed over the neural tube
Nervous system becomes subdivided: spinal cord posteriorly and brain vesicles anteriorly
At which stage of the embryonic development does morphogenesis take place?
What happens?
At tailbud stage, 4-5 weeks
- Cranial and caudal folding arches the embryo into a “comma” shape
- Lateral folding to enclose all forming internal organs in a covering of the ectoderm -> skin
- Major structures of the developing embryo are already formed:
- branchial arches: elements of lower jaw and neck
- heart
- limb bud (limbs)
- eye
- otic vesicle (inner ear)
Embryo has a recognisable appearance
What do we see when comparing embryos of various organisms?
They look similar at the tailbud stage (4-5 weeks).
When and how does the formation of the flexures and subdivisions in the neural tube take place?
Embryonic period (At 5 weeks - 26-35 days)
- Folding of the neural tube leads to formation of flexures
- at the level of the midbrain (mescencephlon)
- at the junction of spinal cord and hindbrain (rombencephalon)
- and at the hindbrain, separating pons from medulla
- more mature morphology
In forebrain (prosencephalon)
- Diencephalon will give rise to nuclei (important collections of neurons): thalamus and hypothalamus
- Telencephalon will give rise to cerebral hemispheres via an extensive folding process
How does differentiation affect human development?
Cells progress from a ‘multipotant’ population, capable of producing a range of cellular derivatives, to cells of specialised identities
What is Waddington’s epigenetic landscape?
A metaphor for development and how cells make ‘decisions’ to arrive at their ‘fates’.
External influences and interactions between groups of cells instruct the cells on their next developmental step, e.g. neural induction: neural plate (ectoderm) is influenced by the mesoderm to develop into the nervous system
What are the aspects of neuronal differentiation?
- Morphology
- Gene expression
- Neurotransmitter
- Axon projections and connections
= characteristics of differentiated neural types
What are the developmental steps that lead to differentiation?
- Neurogenesis: cell division occurs to generate neurons
- Cell migration: young neurons migrate away from ventricular zone
- Axogenesis: neuron starts to develop processes including axons (grow toward target)
- Synaptogenesis: axons connect with their target neurons and other structures (synapses)
- Cell death or pruning: regressive events occur leading to the formation of the mature neuron (brain loses synapses to refine its pathways and balance Glu-GABA ratio)
How does neurogenesis take place?
Generation of neurons from radial glial cells, in the neural tube:
- Neural tube has a ventricular zone (with cerebral spinal fluid, close to ventricular surface) and a mantle zone (close to pial surface covered by meninges)
- In the ventricular zone (VZ), radial glial cells undergo cell divisions repeatedly to expand the progenitor cell population
- Some of these divisions give rise to neurons
- Neurons migrates from ventricular to mantle zone, along the radial glial cell = radial migration
- In mantle zone, further differentiation of the neuron will take place, including extension of the axon
Which neuronal migration generates cortical neurons?
- Radial migration (cells migrating along radial glial cells):
- gives rise to excitatory projection neurons: Glutamate neurons, with long axons
- Tangential migration
- gives rise to inhibitory interneurons: GABA neurons, with short axons
How does synaptogenesis take place?
- Neurexin and Neuroligin (transmembrane proteins) bind the pre and post-synaptic parts together
- They serve as focus for other proteins to cluster together to form the synapse: cadherins and syncams
- Neurexin and Neuroligin recruit specialised groups of proteins into the presynaptic active zones, containing the NT vesicles in the presynaptic terminal
AND coordinate the assembly of postsynaptic densities, containing the scaffolding proteins and NT receptors
