Lecture 20 Flashcards
Neurulation
- Notochord forms from mesoderm cells after gastrulation
- Notochord signals cause ectoderm to fold inwards at neural plate
- Ends of neural plate fuse - forms autonomous neural tube
neuronal specification
- Neurons connected
- Sensory neurons connect with periphery receptors
- Form direction connect with muscle at neuromuscular junction
What are the 3 stages of neuronal development?
- Specification of neurons
- Axon outgrowth
- Synapse formation
Step 1: Neuronal specification
Notch and Delta expressed uniformly in proneural cluster
Delta increases future SOP
Increased delta increases Notch activation in adjacent cells
Increased notch causes increased levels of suppressor of hairless (CSL)
CSL increases expression of enhancer split proteins
Repress achuete-scute proteins -> less delta
Feedback loop further increases Delta in future SOP
bHLH transcription factors activated -> neuronal fate
Step 2 - Neuron outgrowth
- Growth cones migrates towards correct target - actin polymerisation or depolymerisation determines direction of movement
Chemotaxis on long (chemoattraction/repulsion) and short-range cues (Contact attraction/repulsion)
Retinal neurons grow towards netrin
Netrin a chemoattractant and chemorepellent - Netrin 1 and 2
Unc-40 and Unc-5 netrin receptors
Unc-40
Large transmembrane protein
Immunoglobin and fibronectin repeats
Expressed in commissural neurons
Binds strongly to nectin
Antibodies prevent axon growth towards nectin
Unc-5
- Large transmembrane protein
- immunoglobin repeats
- Large intracellular domain
- Modify Unc-40 response
- Unc-5 causes retinal neurons to move away from netrin
Step 3 - making connections
- ARIA released from axon terminal and stimulates ErbB -> increases AChR expression
- Agrin binds LPR4/Musk
- Activates Rapsyn
- Actiaveted Rapsyn binds AChR+
Clustering - > ACh binding
Calcium release -> contraction
Calcium accumulation outside NMJ represses AChR
