Lecture 1 Flashcards
Discovery Road-Map 1…
-Understanding neural circuits
- Identify how neurons & glial cells are arranged in space & time.
- Neurogenesis: extensive remodelling also occurs in times of development e.g. puberty.
- Proccess occurs in Embryogenesis.
Discovery Road-Map 2:
Identifying & Categorising different neurons
Which Where When, Identifying neurons by type, location & time of development.
- Identify the progenitors
Time of Earliest Neuronal Development
Nerve Cells & the pioneering scaffolds
- 4-5 weeks post fertilisation
(unethical & impossible to study this stage).
The Model Organisms for Early Development
- Chick & Mouse
- Nerve cells & scaffolds are essential to life so are highly conserved throughout vertebrates
- Studied via Genetic imaging & experimental manipulation.
Cell division in the Early Embryo
- Highly co-ordinated around 3 specific cell changes…
Cell Differentiation
Cell Migration
Cell shape changes.
- The co-ordination in space & time assembles nerves in the right place.
Process of Differentiation
(differentiation is progressive - at successive cell divisions - slowly reducing potency)
Induction of the multipotent Neural-stem cell.
Regionalisation= diverges into distinct progenitors
Differentiation: of the progenitors into a nerve cell.
Triggers Required for Differentiation (early & late)
Early= External factors:
Late= intrinsic Transcription Factors.
These triggers change gene expression…
As cells reduce in Potency / become more Specialized: they undergo changes to their Transcriptional Profile…
Stem-cell: express genes to regulate their multipotent state
Progenitor: Express genes for faster cell cycles + directing differentiation
Committed/Differentiated Cells: genes for exiting cell cycle & terminating differentiation.
How gene expression is linked to Cell behaviour
Changes in gene expression govern differentiation & also which proteins are made.
The proteins expressed by a cell dictate its behaviour/development.
(she missed most of this slide out).
4 Key Behaviours
Induction/Cell Specification
Regionalisation / Patterning
Cell Differentiation
Morphogenesis (changes in shape)
Early External Factors
released from neighbouring cells
Late Intrinsic TF’s
occurs within the same cell = cell autonomous mechanism
Can provide a memory/instruction for further fate-specification…
for example asymmetric distribution of fate-determining molecules provide daughter cells with different identities.
Studying Embryos:
First step= to Look…
In situ Hybridisation &
Immunochemistry
– can see mRNA & Protein Signatures.
Loss Of Function Studies
A cell secretes a specific signal & a neighbouring cell changes fate in response to this…
Remove the first cell to test whether the signal triggers the differentiation.
Or prevent the Signal/Protein from being detected: by ‘mopping it up’ / degrading it
Or knock out the gene encoding the protein/signal. We now know the specific gene required to change the fate of cell B.
Gain Of Function Studies:
Ectopically placing the cell with the signal…
If a neighbouring cell now assumes the same cell fate (E) induced by the signal - we can conclude that cell A & its signal induces this fate.
