BIOL211 - L20
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- Created by: Katherine
- Created on: 19-04-17 16:10
What are the stages of neural development?
Specification of neurons, axon outgrowth and making synapses.
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Where does notch inhibit neural fate?
In the neurectoderm of drosophila
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If you have a notch mutation, what happens?
There are too many neurons
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Insects are covered in...
Sensory organs (hairs/bristles) - they form part of the nervous system.
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What do sensory bristles contain?
4 cells - trichogen (hair cells), socket cell, sheath cell and sensory neuron
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Where are the sensory bristle cells derived from?
From one sensory organ percursor cell (SOP)
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What do we get if we have too much notch?
missing bristles
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What do we get if we don't have enough Notch?
Extra bristles
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What is notch?
A large transmembrane protein
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What does EGF do?
EGF repeats bind the ligand of Notch
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What is the notch intracellular domain important for?
For signal tranduction - once the lignad has bound to the notch protein, this is what transduces the signal to the nucleus.
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What is in the notch intracellular domain?
Repeat signals called ankyrin repeats
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What are ankyrin repeats for
Important for protein-protein interactions
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The ligands for Notch proteins form a family of proteins called...
DSL proteins - this comes from the names of the first 3 ligans identified (delta, serate and lag2)
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What are DSL proteins
Large transmembrane proteins
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What do DSL proteins have?
EGF repeats in their extracellular domain
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What allows Notch proteins and the DSL ligand to bind together?
Interactions between the EGF repeats in both
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What happens once Notch has bound to its DSL ligand?
It triggers proteolytic cleavage of the notch protein on the cytoplasmic side of the membrane. This releases the intracellular domain of Notch, which duffuses into the nucleus; here it binds to partner protein (CSL). Binding activates transcription
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What sort of protein is notch?
Transmembrane protein
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What do the extracellular domains and it's ligans contain?
EGF repeats
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What does DSL stand for?
Delta, serrate and Lag
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How do Notch and DSL interact?
Via EGF repeats (protein - protein signalling)
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What does ligand binding incude?
The Notch intracellular domain is released
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What does the Notch intracellular domain bind to in the nucleus?
CSL
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What effect does Notch CSL binding to DNA have?
It initiates transcription.
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Are Notch DSL proteins conserved?
Yes, highly
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What is an imaginal disc?
Groups of ectodermal cells
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What are the clusters of cells in the imaginal disc called?
Proneural clusters
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How do we recognise proneural clusters?
They express a protein called Achaete Scute proteins
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Which genes are initially expressed in equal amouns in proneural clusters?
Acaete Scute cells
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What does increased Delta in one cell do to neighbouring cells?
IDK
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What is the effect of increased Notch signalling?
IDK
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What happens because of the feedback loop?
IDK
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How are neurons finally specified?
IDK
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What happens at the cell dendrite?
The cell receives imput from other nerve cells
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What does the growth cone consist of?
Projections (filopodia which contain actin microfilaments)
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What is the role of actin microfilaments in the filopodi?
Actin polymerisation/ depolymerisation determines direction of movement
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What are lamellipodia?
They contain a mesh of actin filaments
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What happens as the growth cone is migrating?
The filopodia are expanding and contracting
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Growth cones respond to..
Chemical signals
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How do growth cones find their target?
Chemotaxis
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What is chemotaxis?
movement of an organism in response to a chemical stimulus
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What is long range chemoattraction?
Moving towards a signal
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What is long range chemorepulsion?
Moving away from a signal
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What is short range contact attraction?
Moving towards an area of high concentration
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WHat is contact replusion?
Moving towards an area of low concentraino.
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Commissural neurons grow towards
The floor plate
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What is netrin?
It is expressed in floor plate cells. IT acts as chemoattractants nad chemorepellants.
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What is Unc 40?
Large transmembrane protein. Immunoglobulin and fibronectin repeats. Commissural neurons fail to grow towards the floor plate in mouse knockouts. Expressed in commissural neurons. Binds strongly to netrin. Antibodies to Unc 40 prevent growth -> netri
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What is unc 5?
Large transmembrane protein, immunoglobulin repeats. large intracellular domain. may modify the response of unc40.
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Expression of Unc 5 causes retinal neurons to move...
Away from netrin
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Do axons stop when they reach the first arget?
No - axons go through the floor plate.
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If an axon passed through a floor plate and then came into contact with another floor plate in a different location, would it change it's path?
No, becuse it has passed through a floor plate. It would only do this if it hadn't been though a floor plate.
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What happens when an axon reaches it's target?
As the growth cone reaches the muscle cell , it starts to differentiate and start branching and forming axon terminals. Inside the axon terminal, lots of vesicles start to form containing neurotransmitter. These are released by exocytosis .
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Where are the neurotransmitters released? And what happens to them?
Into the synaptic cleft where they are taken up by receptors for neurotransmitters.
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How does a signal pass the neuromuscular junction?
Acetylcholine is put into synaptic vesicles. Released by exocytosi. It is released into the synaptic cleft and goes to the AchR receptor
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In the NMJ, How manyy AChR are there?
10,000 - it is clustered but about 10 outside the NMJ
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How does clustering of Ach receptors happen?
Agrin is important - if you add an anti-agrin antibody the number decrease
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What is Agrin
Released by motor neuron of axon terminal. Incorporated into basal lamina of synapse.
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What does the N terminal of Agrin bind to?
Extra cellular matrix
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What does the C terminal bind to?
Receptors on muscle
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One molecule of Agrin can aggregate ...
200 Ach receptors
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Agrin binds via...
LRP4 to MUSK tyrosine kinase
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What does Agrin binding to LRP4 and Musk do?
Initiates a signalling pathway involving Rho and Rac (act as molecular switches and getswitched on when the bind to GTP, in response to agrin binding to the receptor) They signal to Rapsyn. Interaction with Rapsyn brinds the AChR together = cluste
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What is the other route for AChR clustering?
A molecule secreted by axon terminal ARIA (NEUREGULIN) This protein acts as a ligand for a receptor tyrosine kinase (ErbB). Down stream of that is a MAPK pathway. = increased transcription for gene coding for the AChR = clustering
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To which protein does Agrin bind directly?
D
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What does activated Rapsyn bind to?
j
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What other protein is released from the axon terminal to increase AchR expression?
J
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What does Neuregulin bind to?
j
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What repressed AchR gene transcription outside the NMJ?
MapK pathway.
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Other cards in this set
Card 2
Front
Where does notch inhibit neural fate?
Back
In the neurectoderm of drosophila
Card 3
Front
If you have a notch mutation, what happens?
Back
Card 4
Front
Insects are covered in...
Back
Card 5
Front
What do sensory bristles contain?
Back
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