Week 6 Flashcards
Outline how scaffold-guided migration works
- Radial glia provide a scaffold that guides migrating neurons
- Migrating cells form close association with radial glia
- Moves outward in saltatory (stop-start) manner
Radial glia cells are neural progenitor cells that span the whole neuroepithelium with anchor points at both the apical and basal edge
What is chain migration?
- Migrating cells form a continuous chain & slide along one another as they migrate
What is somal translocation (individual migration)
- Migrating neuron extends a single, long process toward the apical surface
- No obvious contact with radial glia
- Process shortens progressively as neuron migrates outward
- Akin to a helicopter winch
Regardless of how a cell migrates, migration as a process has 4 distinct steps:
Initiation
Attachment / Guidance
Locomotion
Detachment / Termination
Discuss the theory of how migration could be initiated and explain how this was inferred
- Initiation is mediated by cell adhesion molecules (CAMs) of which there are 3 main types:
- Cadherins
- Integrins (integrin and laminin)
- N-CAMs
- Dynamic changes are seen in CAM expression before neural crest migration (e.g. Cadherin-6 and N-cadherin are downregulated)
- DOWNREGULATIONof Cadherin-6 and N-cadherin
What are the 2 major mechanisms through which migrating cells can be guided to their location?
- Chemotaxis: subdivided into chemoattraction and chemorepulsion
- Guided by the glial scaffold
What signalling molecule in C.elegans is required for correct nc migration?
And what else is required from the nc cells themselves? What are the genes called?
- Wnt
- The genes egl-20 (encodes a Wnt) and lin-17 (encodes frizzled) are needed in c.elegans for this to work
What are Ephs and Ephrins?
- Ephs are receptor tyrosine kinases (RTKs) and mediate cell-cell interactions, often repulsive
- Ephrins are just the ligands of these receptors
- Ephrin As bind to Eph As and Ephrin Bs bind to Eph Bs
- Signalling is bi-directional
What are the two different progenitor cell areas of the developing cerebellum?
External granule layer (EGL) (outside)
Ventricular Zone (inside)
In the developing cerebellum, cells formed in both the EGL and the VZ must migrate towards each other.
How do they do this / what structure do they use? and what protein is required?
- Bergmann glia traverse most of the cerebellum so are used as a scaffold
- ASTROTACTIN is a crucial CAM in the developing CEREBELLUM. Antibodies that block astrotactin prevent neurons from binding to radial glia
Astrotactin is a CAM involved in radial glia-guided migration in the cerebellum. In the cerebral cortex, radial glial -guided neuronal migration is mediated by what molecule?
Cadherin
Migrating neuronal cells have a very distinct morphology. What is it?
- Long thin process extends out in the direction of travel
- Centrosome positioned ahead of nucleus, in the direction of migration
- Centrosome is attached to the cytoskeleton and so influences morphology
Describe the process of cell shape change during locomotion
- Cell extends process in direction of migration
- Centrosome moves into leading process, trailing end contracts
- Nucleus moves towards centrosome (nucleokinesis), remainder of cell body move forward at the same time
- All mediated by actin-myosin contraction and dependent of the cytoskeleton
Dynamic rearrangement of the cytoskeleton are critical for cell migration.
Describe what happens to microtubules to cause changes in the cytoskeleton?
- Microtubules grow/shrink by gain/loss of TUBULIN subunits
What is Lissencephaly, why does it happen and what genes are associated with it?
- ‘Smooth brain’, lack of folds, sulci, gyri
- Due to issues with migration
- LIS1: Microtubule binding protein, complexes with dynein (microtubule motor)
- Doublecortex (DCX): Microtubule binding protein
- TUBA1A and TUBA1B: Encode alpha and beta tubulin
How is migration terminated?
- Neurons detach from the radial glia scaffold
- This is potentially mediated by stop signals such as reelin
