Neural Crest Cells

Question 1

What is the role of EMT in neural crest migration? What signals regulate it?

Answer 1

EMT allows NCCs to delaminate from the dorsal NT
- Wnt, Notch, BMP & FGF pathways trigger EMT
- downregulate cadherin = cells lose cell-cell adhesion & increase in motility and invasiveness
- upregulation of Snail, Twist, Slug (EMT transcription factors) - promote EMT changes

Question 2

How do Rho GTPases coordinate front-rear polarity during NCC migration?

Answer 2

• Rac1/Cdc42 promote front protrusions
• RhoA drives rear contraction via actomyosin contractions (retractions)
  together drive a forward directional movement of individual NCCs with front-rear polarity

Question 3

What is contact inhibition of locomotion (CIL), and how does it affect NCC migration?

Answer 3

CIL is when cells make contact - repolarise and move away
- RhoA activated at contact site between both cells = induces actomyosin contractions; retraction
- Rac1 inhibited at contact sites = inhibits protrusions
repulsion & repolarisation with CIL ensures migration of NCCs away from each other to guide migratory NCC streams

Question 4

Why is co-attraction important in NCC migration, and what pathway is involved?

Answer 4

co-attraction balances out CIL - prevents cells from scattering after CIL, prevents cell dispersion

involves NCCs secreting C3a (complement protein) & C3aR (receptor) - signalling maintains stream cohesion as NCCs attract each other

Question 5

What is the ‘run and chase’ mechanism in NCC migration?

Answer 5

ectodermal placode cells secrete SDF1 - attracts NCC (“chase”)

upon contact with NCCs - placodes move away (“run”) - creates a dynamic movement pulling NCCs forward with constant ‘run and chase’

Question 6

How do directional migration and collective behaviour emerge in neural crest cells?

Answer 6

integrated signals of CIL, co-attraction, ECM interactions and mechanical environment/confinement promotes overall forward directional movements of NCCs in a stream

• leading NCCs of stream sense environmental cures - form protrusions using Rac1 expression
• leading cells move forward, responding to external signals
• trailing cells follow due to co-attraction, still experience CIL with other NCCs form different streams