Wijnen - Constructing the NS Flashcards
(45 cards)
What is the general developmental timeline of a neuron from progenitor to mature function?
Neurons are born from progenitors and become post-mitotic (stop dividing)
After specification, they migrate and extend processes
One projection becomes the axon (with some early plasticity in fate)
Dendrites form and synapses are created on both dendrites and axon terminals
Synaptic modification and plasticity occur throughout life
Most structural development occurs early postnatally, but synaptic plasticity continues lifelong
What structures does the neural tube and neural crest form during nervous system development?
Neural tube → central nervous system (CNS)
Neural crest → peripheral nervous system (PNS)
What are the main brain regions formed from anterior-posterior patterning of the neural tube?
Telencephalon → cortex, hippocampus, basal ganglia
Diencephalon → retina, thalamus, hypothalamus
Mesencephalon → midbrain
Metencephalon → cerebellum, pons
Myencephalon → medulla
How do Emx2 and Pax6 regulate cortical regionalisation, and what are the effects of their mutual inhibition?
Emx2 is highly expressed posteriorly; Pax6 is expressed anteriorly.
They mutually inhibit each other to sharpen regional boundaries in the developing cortex.
Emx2 inhibits Pax6 → promotes development of visual and auditory cortex (posterior).
Pax6 inhibits Emx2 → promotes somatosensory and frontal cortex (anterior).
Emx2 knockout → reduced posterior cortex, expanded anterior regions.
Pax6 knockout → reduced anterior cortex, expanded posterior visual cortex.
What method was used to track neuronal migration in the mouse visual cortex?
Injection of radioactive tritium at embryonic days (E11–E17)
Autoradiography performed at postnatal day 10
Labelled neurons tracked to determine their final positions
What pattern of neuronal migration was observed in the mouse cortex using tritium labelling?
Neurons labelled at later embryonic days migrated to more superficial cortical layers
Neurons labelled earlier occupied deeper cortical layers
Shows an “inside-out” pattern of cortical development
Why does the “inside-out” cortical layering contradict passive diffusion expectations?
Diffusion would predict earlier injections label neurons that go further
But it’s not diffusion—neurons are born at specific times and actively migrate outward
Later-born neurons bypass earlier-born ones to form outer layers
What cell type gives rise to cortical neurons during development?
Radial glial cells
These divide and produce neurons in waves over time
How do radial glial-derived neurons populate the cortex?
Early-born neurons populate deep layers
Later-born neurons migrate past them to more superficial layers
This forms the laminar structure of the cortex
Where are cortical GABAergic neurons born, and where do they migrate to?
Born in the medial and caudal ganglionic eminences
Migrate tangentially to the neocortex
How do cortical GABAergic neurons migrate?
Travel along the ventricular surface
Migrate from subcortical regions into the cortical plate
What does the lateral ganglionic eminence give rise to?
Neurons that migrate to and populate the olfactory bulb
What principle about neuron origin and function does this migration illustrate?
Neurons can migrate long distances
Place of birth ≠ final functional destination
What are the three methods by which neurones can be generated in vitro from other cells?
Differentiation of embryonic stem cells into neurones using neuronal transcription factors and culture conditions
Reprogramming adult cells (e.g., fibroblasts) into induced pluripotent stem cells (iPSCs) and then differentiating into neurones
Direct conversion of adult cells into neurones by forced expression of neuronal transcription factors and suitable media conditions
What is an induced pluripotent stem cell (iPSC) and how is it generated?
An iPSC is a differentiated adult cell reprogrammed back into a pluripotent state
This is done by expressing embryonic stem cell transcription factors and culturing in stem cell-promoting media
iPSCs can then be differentiated into various cell types, including neurones
What are cerebral organoids and how are they formed in vitro?
Cerebral organoids are 3D cultured structures derived from pluripotent stem cells that mimic some cellular organisation of the brain
They are created by culturing embryoid bodies in Matrigel with neural-inducing factors and mechanical agitation
They exhibit layered neural tissue and can model aspects of neurodevelopment
How do organoid models demonstrate inside-out cortical development similar to the brain?
In brain organoids, newly born neurones migrate past earlier-born neurones, forming outer cortical layers later in development
This mimics in vivo “inside-out” migration observed in mammalian neocortex development
The model provides insights into temporal neurogenesis and lamination
What evidence shows organoid systems can model neuronal migration across distinct brain regions?
Organoids representing different brain regions (e.g., pallium and subpallium) can be fused
Neuronal cells (e.g., Dlx1-expressing interneurons) migrate from one region (green-labelled) into another (red-labelled)
This replicates directed migration patterns seen during embryonic development
What are the four cell types that form a functional sensory hair organ in Drosophila?
The socket cell
The hair cell
The neurone (sensory cell)
The sheath cell (provides structural support)
What is the function and phenotype of the Drosophila numb mutant?
Numb specifies neuronal and sheath cell fate
In numb mutants, all daughter cells become socket or hair cells
Result: the fly has sensory hairs but cannot sense stimuli (hence “numb”)
How does asymmetric distribution of the Numb protein influence cell fate in Drosophila sensory organ precursors?
Numb protein localises to daughter cell 2b during division
Cell 2b becomes a precursor for sheath and neurone cells
Cell 2a, lacking Numb, becomes a precursor for socket and hair cells
What happens to sensory organ cell fates in Drosophila when Numb is absent or overexpressed?
Absent Numb (mutant): all cells adopt socket or hair cell fates → no neuron is formed → fly is unresponsive to touch
Overexpressed Numb: all cells become sheath or neuron cells → no hair or socket is formed → structural support is lost
How do Notch and Delta signalling create patterned cell fates in developing tissues?
Notch and Delta are transmembrane proteins involved in juxtacrine signalling.
Delta on one cell binds Notch on a neighbouring cell, triggering cleavage of Notch and release of its intracellular domain.
This domain acts as a transcription factor, increasing Notch and decreasing Delta expression in that cell.
This creates positive feedback for Notch and negative feedback for Delta, pushing the cell into a “Notch-expressing” fate.
Neighbouring cells that do not receive this signal retain high Delta and become “Delta-expressing” cells.
Result: an alternating Notch–Delta cell pattern from small initial differences — a principle known as lateral inhibition.
What is the source of Sonic Hedgehog (Shh) in the developing spinal cord?
The floor plate secretes Sonic Hedgehog (Shh), establishing a ventral-to-dorsal gradient.
